No abstract

Context:The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.Objective:To report the range of associated conditions identified in the international DSD (I-DSD) Registry.Design, Setting, and Patients:Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.Results:Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.Conclusions:Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.

WHAT'S KNOWN ON THIS SUBJECT: XY disorders of sex development have a diverse etiology and often present with atypical genitalia in the newborn period. Sex assignment in those cases in whom this is marked genital ambiguity is a rare, challenging situation that requires multidisciplinary input. WHAT THIS STUDY ADDS:An international registry has shown temporal changes over the last 3 decades in the practice of sex assignment with a greater proportion of severely affected infants being raised as boys, raising the need for long-term monitoring of these children. abstract BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS:Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS:The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P , .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys.

The effect of long-term GH treatment on bone mass was examined in 32 children with GH deficiency (GHD) aged 7.2-16.3 yr by measuring radial (distal third, single-photon absorptiometry) and lumbar (L2-L4, dual energy x-ray absorptiometry) bone mineral density (BMD) (group A). All patients were longitudinally followed and received recombinant hGH therapy for a mean period of 48.2 +/- 13.2 months. BMD values were corrected for bone age and expressed as Z-score in comparison with normative data. In addition, lumbar BMD and lumbar BMD corrected for the estimated vertebral volumes were assessed in 11 patients with GHD aged 16.0 - 18.7 yr at the time they reached their final height (group B) and, in 17 subjects with familial short stature aged 16.4 - 19.8 yr, as controls (group C) for patients of group B. Patients of group B had received discontinuous treatment with pituitary-derived hGH and subsequently recombinant hGH (total duration of treatment 151.5 +/- 9.7 months). The off-treatment period was 4.7 +/- 2.6 months. Before treatment, patients of group A showed significantly reduced (P < 0.001) radial and lumbar BMD (-1.7 +/- 0.4 Z-score and -1.5 +/- 0.5 Z-score, respectively) compared with normative data. During treatment, radial and lumbar BMD Z-scores improved significantly (P < 0.001); in the patients treated for the longest time, the BMD was within 0.5 SD of age-matched mean levels. In patients of group B, lumbar BMD and lumbar BMD corrected for the estimated vertebral volumes were significantly reduced in comparison with subjects of group C (-1.2 +/- 0.4 Z-score and -1.0 +/- 0.4 Z-score, P < 0.01 and P < 0.03, respectively). The results show that children with GHD have reduced BMD. Optimal GH treatment improves BMD, whereas inappropriate treatment is a main cause of reduced BMD at time of final height. These findings suggest an important role of GH therapy in the attainment of peak bone mass in children with GHD. GH treatment should be continued until the attainment of peak bone mass irrespective of the height achieved.

No abstract