Xq26.3-q27.1 duplication including SOX3 gene in a Chinese boy with hypopituitarism: case report and two years treatment follow up.

BACKGROUND: SOX3 is essential for pituitary development normally at the earliest stages of development. In humans, variants of SOX3 can cause X-linked hypopituitarism with various clinical manifestations, with or without mental retardation. CASE PRESENTATION: We present an 8-year-old Chinese patient with congenital hypopituitarism who had a 6.180 Mb duplication on Xq26.3q27.1 including SOX3, F9, and eight other contiguous genes. The main complains of the boy was short stature. His height was 90.1 cm (- 5.87SDS), weight 11.5 kg (- 5.25SDS). He developed growth hormone (GH) deficiency, cryptorchidism and low thyroid function. Pituitary magnetic resonance imaging revealed the pituitary dysplasia. After diagnosis, levothyroxine was given for one month first, and the thyroid function basically returned to normal, but the growth situation did not improve at all. Then recombinant human GH was given, his height, growth rate and height SDS were improved significantly in the 2 years follow-up. The level of height SDS improved from - 5.87 SDS before treatment to - 3.27 SDS after the first year of treatment and - 1.78 SDS after the second years of treatment. Gonadal function and long-term prognosis of the patient still need further observation and follow-up. CONCLUSIONS: This is the first case of Chinese male patient with multiple hypophysis dysfunction caused by SOX3 duplication, which will expand the range of phenotypes observed in patients with duplication of SOX3.

Analysis of the Screening Results for Congenital Adrenal Hyperplasia Involving 7.85 Million Newborns in China: A Systematic Review and Meta-Analysis.

Background: Congenital adrenal hyperplasia (CAH) is a group of congenital genetic diseases caused by defective steroidogenesis. Our study aims to systematically analyze the screening results for CAH in Chinese newborns. Methods: Studies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to September, 2020. Meta-analysis was performed after quality assessment and data extraction. Results: After a review of 2 694 articles, we included 41 studies enrolling 7 853 756 newborns. In our study, we found that the incidence of CAH in China was 0.43‱ [95% confidence intervals(CI), (0.39‱, 0.48‱)], or 1/23 024 [95%CI, (1/25 757,1/20 815)]. 27 studies were included for analysis of the screening positive rate, which gave a rate of 0.66% [95%CI, (0.54%, 0.78%)]. As for the recall rate of positive cases, 17 studies were included and showed that the recall rate reached 86.17% [95%CI, (82.70%, 89.64%)]. Among the CAH patients, the ratio of males to females was 1.92:1 (119:62), and the ratio of salt wasting (SW) to simple virilization (SV) type was 3.25:1 (104:32). The average 17-hydroxyprogesterone (17-OHP) value of CAH was 393.40 ± 291.85 nmol/L (Range 33-1 300 nmol/L); there was no significant difference between male and female patients (437.17 ± 297.27 nmol/L v.s. 322.25 ± 293.04 nmol/L, P=0.16), but a significant difference was found between SW and SV patients (483.29 ± 330.07 nmol/L v.s. 73.80 ± 7.83nmol/L, P=0.04). Conclusion: We systematically analyzed the current situation of neonatal CAH screening in China, which will deepen our understanding for future CAH screening and early diagnosis.

Novel truncating variant of PPM1D penultimate exon in a Chinese patient with Jansen-de Vries syndrome.

BACKGROUND: Jansen-de Vries syndrome is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the last and penultimate exons of the PPM1D gene. It is characterized by delayed psychomotor development, intellectual disability with speech delay, behavioral abnormalities, and dysmorphic features. Up to date, only 17 affected patients have been reported worldwide (no report in Chinese). METHODS: Here, we analyzed the clinical data and genetic test results of a Chinese patient with Jansen-de Vries syndrome admitted in our hospital in May 2019. RESULTS: We report a 9-month-old boy carrying a pathogenic variant (c.1254_1255del, p.(V419Qfs*14)) in PPM1D exon 5, which can account for his phenotype. Most of his clinical features overlap with the reported phenotype, such as growth retardation, feeding difficulties, constipation, congenital abnormalities (such as atrial septal defect, ventricular septal defect, and patent ductus arteriosus), small hands and feet with broad forehead, low-set posteriorly rotated ears, wide mouth with thin upper lip and pointed chin; however, he also presented with additional features like hepatomegaly and left inguinal hernia. CONCLUSION: This is the first published case of Jansen-de Vries syndrome in Chinese population, which will help us to enrich the clinical spectrum of this syndrome.

Do children with mental disorders have higher prevalence of hypovitaminosis D?

Inadequate vitamin D level is associated with various adverse medical outcomes. There is a growing concern that insufficient vitamin D may play a role in the development of psychiatric symptoms. This study aims to answer the question: do children with mental disorders have a higher prevalence of hypovitaminosis D? A retrospective chart review examined 25 hydroxyvitamin D (25(OH)D) levels in youth ages 7 to 17 (n=67) at two Oregon psychiatric residential facilities. Vitamin D deficiency is defined as <20 ng/ml and insufficiency as <30 ng/ml. Diagnoses were organized into six categories. 25(OH)D levels were compared across genders and diagnostic groups using a two-sample t-test and ANOVA, respectively. Statistical differences in prevalence across diagnostic categories were calculated using a Pearson chi-square test. Using the data from Saintonge's NHANES III study on healthy US children for comparison, 21% of our cohorts were found to be vitamin D deficient and 64% insufficient, in contrast to 14% and 48%, respectively. While our results are not statistically significant, mainly because of small sample size, the overall mean 25(OH)D level in our cohort was insufficient (27.59 ± 9.35 ng/ml), compared to a sufficient mean value of 32.1 ng/ml in the general population. No statistical significant difference was found in the prevalence across diagnostic categories. This study found that children with psychiatric disorders might have a higher prevalence of hypovitaminosis D than the general pediatric population. Although a causal relationship between hypovitaminosis D and psychiatric disorders cannot be derived based on the study design, our study provides initial descriptive data on the prevalence of hypovitaminosis D in children with psychiatric disorders, which has not been previously reported to our knowledge. Prospective studies with a larger sample size and controlled variables would allow more precise analysis of the relationship between hypovitaminosis D and childhood mental disorders.