Birth Weight in Different Etiologies of Disorders of Sex Development

Abstract

It is well known that birth weight (BW) in boys is higher than in girls in the general population. Differences in BW between sexes have been reported in humans and in nonhuman primate species (1). Although the cause of BW difference is unknown, it has been proposed that the Y chromosome and prenatal androgen action may play a role (2, 3).

The effect of androgens on fetal growth and BW difference between sexes has been reported in previous studies. Although some studies have shown that BW difference is dependent on fetal androgens, other studies reported that it is not generated by action of androgens (3–6).

It has been demonstrated that BW difference becomes obvious in the fetus in the first trimester (7). de Zegher et al. (4) reported that BW difference is developed before the third trimester and is relatively less pronounced during the latter part of gestation.

The aim of the current study was to assess the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the BW in relation to androgen action.

Patients and Methods

Data regarding diagnosis, BW, gestational age, karyotype constitution, and concomitant conditions (abnormalities other than genital system) were collected from 15 centers in 9 countries (Turkey, United Kingdom, Germany, The Netherlands, Italy, Czech Republic, Belgium, Sweden, and Poland) reported in the International Disorders of Sex Development (I-DSD) Registry (www.I-DSD.org). If data on gestational ages or BW were not available in the registry, clinicians were asked to report the missing data. Only patients with 46,XY DSD and 46,XX DSD conditions were included; cases with sex chromosome DSD were excluded. Cases were evaluated according to classification in the I-DSD registry given in Table 1, including disorders of gonadal development, androgen synthesis, androgen excess, androgen action, nonspecific disorders of undermasculinization, and Leydig cell defect. BWs of cases were expressed as standard deviation score (SDS) for gestational age according to national references for each country for the same karyotype (8–16). In the disorder of androgen action group, BWs of cases were expressed as SDS for gestational age for boys and, taking into consideration the lack of effect of androgens, for girls. Small for gestational age (SGA) was defined as BW less than −2 SDS for gestational age.

In the I-DSD groups, BW-SDS was evaluated according to karyotype. In the disorders of androgen action group, BW-SDS was also evaluated with respect to the presence or absence of an androgen receptor gene (AR) mutation. We evaluated concomitant conditions in DSD cases and the relationship of SGA with other concomitant conditions. We excluded known DSD syndromic conditions and anomalies that are acquired as the consequences of the management of the disorders, such as short stature in congenital adrenal hyperplasia (CAH).

Statistical analysis was performed using SPSS Statistical Package version 15 (SPSS Inc., Chicago, IL). Results are reported as means ± SD. Mean BW-SDS values of groups were compared with population average value (BW-SDS = 0) by 1-sample t tests. Fisher’s exact test was used to compare the proportion of SGA in the groups. Two-tailed P values were calculated. Statistical significance was accepted as P < 0.05.

Results

Of 649 accessible cases in the registry, 533 were suitable for evaluation [Turkey (n = 329), United Kingdom (n = 28), Germany (n = 14), The Netherlands (n = 49), Italy (n = 39), Czech Republic (n = 35), Belgium (n = 19), Sweden (n = 13), Poland (n = 7)]. A total of 400 (75%) cases had a 46,XY karyotype, and 133 (25%) cases had a 46,XX karyotype. SGA was detected in 80 cases (15%). Significantly more cases with the 46,XY karyotype (17.8%) were born SGA than cases with the 46,XX karyotype (6.7%) (P = 0.001). Numbers of cases in each I-DSD diagnostic group in the study are shown in Fig. 1.

Figure 1.

Number of cases according to I-DSD registry groups in the 46,XY and the 46,XX karyotype. 3BHSD, 3β-hydroxysteroid dehydrogenase deficiency; 11BHD, 11β-hydroxylase deficiency; 17BHSD, 17β-hydroxysteroid dehydrogenase deficiency; 21HD, 21 hydroxylase deficiency; CGA, complex genital anomalies; CGD, complete gonadal dysgenesis; CYP17D, CYP17 deficiency, EMS, external masculinization score, LCH, Leydig cell hypoplasia; PGD, partial gonadal dysgenesis; POR, P450 oxidoreductase deficiency; SRD5A2, 5α reductase deficiency; STAR, steroidogenic acute regulatory protein deficiency.

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The analysis according to the registry’s subgroups showed the following distribution:

• •

  In disorders of gonadal development group: Twelve cases (19.4%) were 46,XX, and 50 cases (80.6%) were 46,XY (Table 2). None of 46,XX cases was born SGA, whereas 14% (n = 7) of cases with 46,XY karyotype were born SGA. Mean BW-SDS values of cases with 46,XX were similar to the national references for girls (P = 0.87). Although not statistically significant, mean BW-SDS values of 50 46,XY cases showed a lower trend compared with the national references for boys (P = 0.056). However, after excluding SGA cases, mean BW-SDS values of 46,XY cases were not different from national references for boys (mean BW-SDS: −0.1 ± 0.9; P = 0.31).

  Table 2.

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  BW-SDS and Frequency of SGA Birth in 46,XX and 46,XY Cases According to Classification in the I-DSD Registry

  Disorder Type .	46,XX (n) .	46,XY (n) .	BW-SDS, mean ± SD (95% CI) .				SGA, n (%) .
  			46,XX .	P Valuea .	46,XY .	P Valueb .	46,XX .	46,XY .
  Gonadal development	12	50	−0.03 ± 0.75 (−0.51 to 0.44)	0.87	−0.29 ± 1.07 (−0.60 to 0.05)	0.056	0	7 (14)
  Androgen synthesis	10	70	−0.01 ± 0.5 (−0.37 to 0.34)	0.93	−0.16 ± 1.0 (−0.40 to 0.07)	0.17	0	7 (10)
  Androgen excess	111	59	−0.08 ± 1.15 (−0.29 to 0.13)	0.46	−0.14 ± 1.14 (−0.48 to 0.16)	0.37	9 (8.1)	4 (6.8)
  Androgen action	—	170	—		−0.90 ± 1.53 (−1.17 to 0.71)	0.001	—	40 (22.9)
  					−0.58 ± 1.6c		—
  AR mutation positive		27	—	—	−0.36 ± 1.51d	0.21	—	4 (14.8)e
  					−0.01 ± 1.6f
  AR mutation negative		77	—	—	−1.38 ± 1.75d	0.001		31 (40.3)e
  Leydig cell defects	—	8	—	—	−0.68 ± 1.61 (−2.02 to 0.66)	0.27	—	1 (12.5)
  Nonspecific disorder of undermasculinization	—	34	—	—	−1.31 ± 1.45 (−1.81 to −0.80)	0.001	—	12 (35.3)
  Isolated hypospadias		11	—	—	−1.48 ± 1.84	0.024	—	5 (45.5)

  Disorder Type .	46,XX (n) .	46,XY (n) .	BW-SDS, mean ± SD (95% CI) .				SGA, n (%) .
  			46,XX .	P Valuea .	46,XY .	P Valueb .	46,XX .	46,XY .
  Gonadal development	12	50	−0.03 ± 0.75 (−0.51 to 0.44)	0.87	−0.29 ± 1.07 (−0.60 to 0.05)	0.056	0	7 (14)
  Androgen synthesis	10	70	−0.01 ± 0.5 (−0.37 to 0.34)	0.93	−0.16 ± 1.0 (−0.40 to 0.07)	0.17	0	7 (10)
  Androgen excess	111	59	−0.08 ± 1.15 (−0.29 to 0.13)	0.46	−0.14 ± 1.14 (−0.48 to 0.16)	0.37	9 (8.1)	4 (6.8)
  Androgen action	—	170	—		−0.90 ± 1.53 (−1.17 to 0.71)	0.001	—	40 (22.9)
  					−0.58 ± 1.6c		—
  AR mutation positive		27	—	—	−0.36 ± 1.51d	0.21	—	4 (14.8)e
  					−0.01 ± 1.6f
  AR mutation negative		77	—	—	−1.38 ± 1.75d	0.001		31 (40.3)e
  Leydig cell defects	—	8	—	—	−0.68 ± 1.61 (−2.02 to 0.66)	0.27	—	1 (12.5)
  Nonspecific disorder of undermasculinization	—	34	—	—	−1.31 ± 1.45 (−1.81 to −0.80)	0.001	—	12 (35.3)
  Isolated hypospadias		11	—	—	−1.48 ± 1.84	0.024	—	5 (45.5)

  Abbreviations: CI, confidence interval.

  ^a

  One-sample t test: comparison of mean BW-SDS of 46,XX cases to the population average value for girls (BW-SDS = 0);

  ^b

  One-sample t test: comparison of mean BW-SDS of 46,XY cases to the population average value for boys (BW-SDS = 0).

  ^c

  BWs of cases expressed as SDS for girls and compared with national references for girls (1-sample t test; P = 0.001).

  ^d

  Comparison of BW-SDS of AR mutation–positive and –negative groups (P = 0.009).

  ^e

  Comparison of SGA frequency between AR mutation–positive and –negative groups (P = 0.018).

  ^f

  BWs of AR mutation–positive cases expressed as SDS for girls and compared with national references for girls (1-sample t test; P = 0.97).

  Table 2.

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  BW-SDS and Frequency of SGA Birth in 46,XX and 46,XY Cases According to Classification in the I-DSD Registry

  Disorder Type .	46,XX (n) .	46,XY (n) .	BW-SDS, mean ± SD (95% CI) .				SGA, n (%) .
  			46,XX .	P Valuea .	46,XY .	P Valueb .	46,XX .	46,XY .
  Gonadal development	12	50	−0.03 ± 0.75 (−0.51 to 0.44)	0.87	−0.29 ± 1.07 (−0.60 to 0.05)	0.056	0	7 (14)
  Androgen synthesis	10	70	−0.01 ± 0.5 (−0.37 to 0.34)	0.93	−0.16 ± 1.0 (−0.40 to 0.07)	0.17	0	7 (10)
  Androgen excess	111	59	−0.08 ± 1.15 (−0.29 to 0.13)	0.46	−0.14 ± 1.14 (−0.48 to 0.16)	0.37	9 (8.1)	4 (6.8)
  Androgen action	—	170	—		−0.90 ± 1.53 (−1.17 to 0.71)	0.001	—	40 (22.9)
  					−0.58 ± 1.6c		—
  AR mutation positive		27	—	—	−0.36 ± 1.51d	0.21	—	4 (14.8)e
  					−0.01 ± 1.6f
  AR mutation negative		77	—	—	−1.38 ± 1.75d	0.001		31 (40.3)e
  Leydig cell defects	—	8	—	—	−0.68 ± 1.61 (−2.02 to 0.66)	0.27	—	1 (12.5)
  Nonspecific disorder of undermasculinization	—	34	—	—	−1.31 ± 1.45 (−1.81 to −0.80)	0.001	—	12 (35.3)
  Isolated hypospadias		11	—	—	−1.48 ± 1.84	0.024	—	5 (45.5)

  Disorder Type .	46,XX (n) .	46,XY (n) .	BW-SDS, mean ± SD (95% CI) .				SGA, n (%) .
  			46,XX .	P Valuea .	46,XY .	P Valueb .	46,XX .	46,XY .
  Gonadal development	12	50	−0.03 ± 0.75 (−0.51 to 0.44)	0.87	−0.29 ± 1.07 (−0.60 to 0.05)	0.056	0	7 (14)
  Androgen synthesis	10	70	−0.01 ± 0.5 (−0.37 to 0.34)	0.93	−0.16 ± 1.0 (−0.40 to 0.07)	0.17	0	7 (10)
  Androgen excess	111	59	−0.08 ± 1.15 (−0.29 to 0.13)	0.46	−0.14 ± 1.14 (−0.48 to 0.16)	0.37	9 (8.1)	4 (6.8)
  Androgen action	—	170	—		−0.90 ± 1.53 (−1.17 to 0.71)	0.001	—	40 (22.9)
  					−0.58 ± 1.6c		—
  AR mutation positive		27	—	—	−0.36 ± 1.51d	0.21	—	4 (14.8)e
  					−0.01 ± 1.6f
  AR mutation negative		77	—	—	−1.38 ± 1.75d	0.001		31 (40.3)e
  Leydig cell defects	—	8	—	—	−0.68 ± 1.61 (−2.02 to 0.66)	0.27	—	1 (12.5)
  Nonspecific disorder of undermasculinization	—	34	—	—	−1.31 ± 1.45 (−1.81 to −0.80)	0.001	—	12 (35.3)
  Isolated hypospadias		11	—	—	−1.48 ± 1.84	0.024	—	5 (45.5)

  Abbreviations: CI, confidence interval.

  ^a

  One-sample t test: comparison of mean BW-SDS of 46,XX cases to the population average value for girls (BW-SDS = 0);

  ^b

  One-sample t test: comparison of mean BW-SDS of 46,XY cases to the population average value for boys (BW-SDS = 0).

  ^c

  BWs of cases expressed as SDS for girls and compared with national references for girls (1-sample t test; P = 0.001).

  ^d

  Comparison of BW-SDS of AR mutation–positive and –negative groups (P = 0.009).

  ^e

  Comparison of SGA frequency between AR mutation–positive and –negative groups (P = 0.018).

  ^f

  BWs of AR mutation–positive cases expressed as SDS for girls and compared with national references for girls (1-sample t test; P = 0.97).

• •

  Androgen synthesis disorders: Eighty cases had a disorder of androgen synthesis; 10 (12.5%) of these cases were 46,XX, and 70 (87.5%) were 46,XY. Mean BW-SDS values of the 46,XX and 46,XY cases were normal for girls and boys compared with the national references (P = 0.93 and P = 0.17, respectively) (Table 2). Only 7 (10%) cases with 46,XY were born SGA (Table 2).

• •

  Androgen excess disorders: In the 170 cases of disorders of androgen excess group, the mean BW-SDS values of 111 cases with 46,XX were not different when compared with the national references for girls (P = 0.46) (Table 2). Similarly, the BW-SDS values of 59 cases with the 46,XY karyotype were not different compared with the national references for boys (P = 0.37) (Table 2). The frequency of cases born SGA was 8.1% in the 46,XX karyotype and 6.8% in the 46,XY karyotype.

• •
  Androgen action disorders: Of the 179 cases classified as having disorders of androgen action, 113 patients were screened for AR mutations (Fig. 2). Results of 9 patients (1 AR mutation positive, 8 AR mutation negative) reported previously (5) were excluded from this study. Within the remaining 104 cases, AR mutation was reported in 27 cases [10 complete androgen insensitivity syndrome (CAIS) and 17 partial androgen insensitivity syndrome (PAIS)]. AR mutation was reported in 90% of clinically classified CAIS cases and in 18.3% of cases clinically classified as PAIS.

  

  Figure 2.

  The number of patients in disorders of androgen action group with respect to AR mutation.

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  • Mean BW-SDS values of cases with disorders of androgen action regardless of AR mutation were substantially lower compared with national references for boys and girls [−0.90 ± 1.5 (P = 0.001) and −0.58 ± 1.6 (P = 0.001), respectively]. The mean BW-SDS values of AR mutation–positive cases were higher than the mean BW-SDS values of AR mutation–negative cases (P = 0.009) (Table 2). Mean BW-SDS values of AR mutation–positive cases were not different from the national references for boys and girls but were slightly higher with respect to national references for girls [−0.36 ± 1.5 (P = 0.21) compared with boys and −0.01 ± 1.6 (P = 0.97) compared with girls]. Patients with both CAIS and PAIS and with a proven AR mutation had BW-SDS values similar to healthy boys and girls. SGA birth was significantly less frequent in AR mutation–positive cases compared with AR mutation–negative cases (14.8% and 40.3%, respectively; P = 0.018).

• •

  Leydig cell defects: Eight cases with Leydig cell defect were recorded in the registry. No significant difference in BW-SDS was found when compared with normal references for boys (Table 2). SGA birth was detected in only 1 case.

• •

  Nonspecific diagnosis: The group of nonspecific disorder of undermasculinization in the I-DSD registry is heterogeneous and includes diagnostic groups summarized in Table 1. In this group, the frequency of SGA birth was very high: 12 out of 34 cases (35.3%) were born SGA (Table 2). Mean BW-SDS values of patients in this group were significantly lower compared with normal boys (P = 0.001). Isolated hypospadias was found in 11 cases, of whom 5 were born SGA. Mean BW-SDS values of 11 cases with isolated hypospadias were lower than the national references for boys (P = 0.024) (Table 2).

Concomitant conditions were reported in 108 (27.6%) cases of 46,XY DSD and in 14 (10.5%) cases of 46,XX DSD (Table 3). Concomitant conditions were more frequently recorded in cases born SGA than in patients born appropriate for gestational age (25% and 9.5%, respectively; P = 0.0003) (Table 3). In the disorders of androgen action group, concomitant conditions were found in 31.8% of patients, and concomitant conditions were more frequent in the AR mutation–negative group than in the AR mutation–positive group (49.4% and 22.2%, respectively; P = 0.02).

Discussion

The use of the I-DSD Registry has enabled us to explore the relationship between the sexual dimorphism in BW and the role of prenatal androgens in a large cohort of 533 cases with different forms of DSD. Overall, our results demonstrate that the sexual dimorphism in BW cannot be explained by the effects of prenatal androgen action.

BWs in both karyotypes in disorders of gonadal development, disorders of androgen synthesis, disorders of androgen excess groups, and disorders of androgen action cases with a confirmed AR gene mutation were not different among healthy children with the same karyotype. The disorders of androgen excess group included mainly cases with 21-hydroxylase deficiency and 11β-hydroxylase deficiency. These cases have prolonged exposure to high levels of androgens during fetal life, which may affect BW. However, BW in cases with androgen excess was similar compared with normal children with the same karyotype, suggesting that excess androgen does not increase the BW. Similarly, cases with disorders of gonadal development and disorders of androgen synthesis, in which low fetal concentration of androgens is expected, did not show a decrease in BWs. The BWs in these cases were within the normal reference range for chromosomal sex. In our cohort, despite androgen resistance, patients with CAIS and PAIS with confirmed AR mutations had comparable BWs to unaffected boys with the 46,XY karyotype. Although not significantly different from BW-SDS in healthy boys, BW-SDS in both CAIS and PAIS is closer to female reference ranges. This finding seems reasonable considering the normal difference in BW-SDS of two genders in normal population.

The role of prenatal androgen action on BW is not fully understood. It has been reported that 46,XY children with CAIS have a BW comparable to that of girls with the 46,XX karyotype, and it has been suggested that the difference in BW between girls and boys is attributable to androgens (3). In contrast, another study from the United Kingdom and Sweden hypothesized that the BWs of patients were independent of androgen exposure during the prenatal period because patients with CAIS had a BW similar to unaffected boys with the 46,XY karyotype (6). In addition, the same study demonstrated no significant effect on the BW in patients with CAH with the 46,XX karyotype, a finding that was confirmed in our study. Subtype data of patients with CAH were not available in the current study, and we did not evaluate BW according to clinical form of CAH. In the study from the United Kingdom and Sweden, BW did not vary according to the severity of CAH (6). On the other hand, Balsamo et al. (17) reported increased mean BW only in girls with classical CAH born at 39.0 ± 1.1 weeks compared with the national birth data. However, BW in a salt-wasting group was lower than in a simple-virilizing group. In another report, greater gestational age was found to be correlated with the severity of CAH, which may be another factor affecting BW (18).

The frequency of AR mutation positivity in cases diagnosed as PAIS clinically is reported to be 14% to 22% (5, 19, 20). Similar to the literature, in the disorder of androgen action group in our cohort, AR mutation positivity was found in 18.3% of clinically diagnosed PAIS cases.

In our total cohort, SGA was present in 15% of cases, with a high prevalence of SGA in 46,XY patients with DSD, especially in patients with impaired androgen action with the absence of a mutation in the AR with and in patients with nonspecific disorders of undermasculinization. The frequency of births associated with SGA based on BW and/or birth length less than −2 SD is reported to be 5.4% in Western Europe and 4.2% in Turkey (21, 22). The frequency of SGA in DSD subgroups is higher than in the general population except for the androgen excess group. However, considering the relatively small number of cases, it may be difficult to make a comparison with the general population. When BWs in different DSD subgroups were compared, the BWs of AR mutation–positive patients were similar to typical boys, whereas the BWs of AR mutation–negative patients were significantly lower than AR mutation–positive patients, in accordance with previous publications (5, 6). Furthermore, the frequency of SGA births in the AR mutation–negative group was markedly high (40.3%) compared with AR mutation–positive cases (14.8%). Similar to our results, a higher frequency of SGA births was found in AR mutation–negative infants (37%) compared with AR mutation–positive infants (6%) (5).

In a recent study from the I-DSD consortium, it was reported that genetically confirmed cases of PAIS are more likely to have a worse medical and surgical outcome as young men compared with cases with a similar phenotype at birth but in whom no AR mutation could be detected. Routine genetic analysis of AR in boys suspected of PAIS is recommended to guide long-term prognosis and to tailor management (23). At birth, although clinical phenotype and laboratory tests are not discriminative, BW-SDS adjusted for gestational age could be helpful for considering AR analysis (i.e., AR sequencing should specifically be considered in children born appropriate for gestational age). Patients who have no AR mutation may represent a different diagnostic (sub)group. The BWs of AR mutation–positive patients with both CAIS and PAIS were not statistically different from typical boys or girls, whereas the BWs of AR mutation–negative patients were significantly lower than AR mutation–positive patients, in accordance with previous publications (5, 6).

Generally, in 46,XY DSD no genetic cause can be determined in approximately 30% to 40% of cases (24). Approximately 30% of these cases are related with low BW (25), and about 30% of undetermined 46,XY DSD cases had BW lower than 2500 g (26). There seems to be a substantial correlation between SGA birth and 46,XY DSD, more specifically with severe undermasculinization in the presence of an apparently normal testicular function (and action) (2, 27). Audi et al. (19) reported that in 52 patients without any detected mutation, 11 (21.1%) patients born prematurely and accompanied or not with intrauterine growth retardation had ambiguous genitalia. Low BW and SGA are well-established risk factors for hypospadias, and the risk for cryptorchidism and hypospadias increases with decreasing BW, independent of gestational age (27, 28).

The nature of the relationship between genital abnormalities and restricted intrauterine growth is currently not known. However, numerous factors have been hypothesized to play a role, including genetic, placental dysfunction, and androgen deficiency in early pregnancy and environmental factors such as diethylstilbestrol, phytoestrogen, phthalates, and pesticides (2, 27–30). It remains unknown whether there is a causal association or a common pathogenic base. A dysfunctional placenta may provide insufficient nutrients and placental human chorionic gonadotropin to the fetus and lead to growth retardation and hypospadias because placental human chorionic gonadotropin during the first 14 weeks of gestation controls fetal testosterone synthesis and secretion (27, 29, 30). At the same time, the fetal masculinization programming window of the reproductive tract occurs between gestational weeks 8 to 14 in humans (31).

Frequency of concomitant conditions in DSD cases were reported in 37.5% in a German cohort (32) and in 27% in a previous report from the I-DSD Registry (33). In our cohort, similar to the previous two studies, we found a frequency of 23.3% concomitant conditions in 46,XX and 46,XY DSD. Our results confirm that concomitant conditions are frequent in DSD, especially in the 46,XY DSD and disorders of gonadal development group, in the AR negative disorder of androgen action group, and in the nonspecific undermasculinization group.

In confirming some of the findings in previous studies, the strength of this study is the large number of DSD cases analyzed by BW for gestational age. All data were cross-checked with the individual clinicians to minimize registration errors. Furthermore, substantial numbers were analyzed across the range of major causes of DSD.

BW is a more reliable and easier measurement to obtain in newborns than birth length. BW dimorphism is also reported to parallel birth length (34, 35). We show that sex affects BW independently of fetal androgens. Although the reasons of sexual dimorphism in BW are unclear, it has been reported that fetal sex is associated with maternal glucose metabolism and insulin sensitivity as well as differential placentation probably due to imprinting of placental genes (36–40). These fetal sex effects during pregnancy may be a factor in the observed differences in BW.

In conclusion, BW dimorphism is unlikely to be dependent on fetal androgen action. Our results agree with previous studies showing that nonspecific disorders of undermasculinization in 46,XY DSD are associated with fetal growth restriction, SGA birth, and concomitant conditions. Although AR mutation–negative cases have similar clinical phenotype and laboratory tests compared with AR mutation–positive cases, they have significantly lower BW, higher SGA birth frequency, and a higher prevalence of concomitant conditions when compared with AR mutation–positive cases. Placental insufficiency/fetal growth restriction can result in severe undermasculinization with normal testicular androgen production, thus mimicking PAIS. For the diagnostic clarity of classification of DSD, our results underscore that the diagnosis of PAIS should be reserved only for those cases with a proven AR mutation.

Abbreviations:

 
• AR

  androgen receptor gene

 
• BW

  birth weight

 
• CAH

  congenital adrenal hyperplasia

 
• CAIS

  complete androgen insensitivity syndrome

 
• DSD

  disorders of sex development

 
• I-DSD

  International Disorders of Sex Development

 
• PAIS

  partial androgen insensitivity syndrome

 
• SDS

  standard deviation score

 
• SGA

  small for gestational age

Acknowledgments

Disclosure Summary: The authors have nothing to disclose.

References

Author notes