45,X/46,X,psu dic(Y) Gonadal Dysgenesis: Influence of the Two Cell Lines on the Clinical Phenotype, Including Gonadal Histology

A child born with ambiguous genitalia (Prader III) was found to have a 45,X[92.2%]/46,X,psu dic(Y)(p12)[7.8%] karyotype in peripheral blood lymphocytes. The testosterone level was consistent with that of a normal male; however, gonadotropins were elevated. Ultrasound and endoscopy of the urogenital sinus revealed well-developed Müllerian structures. At 3.5 months, the child was operated for right-sided incarcerated hernia, and the gonad situated at the inguinal region was biopsied and classified as primitive testis. Based on the presence of Müllerian structures, anatomy of external genitalia and wish of the parents, the child was assigned female gender. She underwent removal of the left gonad at 4 months during another acute surgery; histology was similar to the right gonad. The rest of the right gonad was removed at 16 months, and feminizing genitoplasty took place at 3 years. The right and left gonad contained 28 and 22% of cells with a Y chromosome, respectively. During further histological examination, dysgenetic features of the gonads were discovered. Some germ cells displayed abnormal development based on the specific expression of immunohistochemical markers (OCT3/4, TSPY, KITLG), indicating a possible risk for future malignant germ cell tumor development. Contribution of the 45,X cell line to the phenotype was also observed: the patient developed celiac disease, and her growth pattern resembled that of Turner syndrome responding to growth hormone treatment.</jats:p

The effect of parental age on NF1 patients in Turkey

Neurofibromatosis type 1 (NF1) is the most common neurogenetic disorder worldwide, and its clinical presentations are highly variable. NF1 is caused by mutations in the NF1 gene, and 50% of NF1 cases are sporadic, which occur in the absence of a family history of the disease and usually result from a new mutation in the germline of a parent. Advanced paternal age may increase the risk for germinal NF1 mutations; however, some dominant conditions, including neurofibromatosis, have shown a lesser association with paternal age, although there are conflicting reports in the literature. We investigated the effects of paternal and maternal age in 241 NF1 patients (121 sporadic and 120 familial cases) who were seen in Hacettepe hospital, a reference center for genetic diseases in Turkey. For statistical analysis, Spearman’s and Chi-square tests were used. In this study, we evaluated paternal and maternal age at birth in sporadic and familial cases of NF1. We also compared the effect of parental age on the appearance and coexistence of various NF1 symptoms. There were no significant statistical differences between paternal age and coexistence of the NF1 symptoms. However, a slightly negative correlation was observed between paternal age and the coexistence of NF1 symptoms in familial cases (p < 0.05). We did not find strong evidence for the effect of parental age on the clinical severity of NF1

Comparison of response to 2-years’ growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies

<p>Abstract</p> <p>Background</p> <p>Few studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark).</p> <p>Methods</p> <p>Analysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS) and NovoNet®/American Norditropin® Studies: Web-enabled Research (ANSWER) Program®.</p> <p>Results</p> <p>4,582 children aged <18 years were included: IGHD, n = 3,298; SGA, n = 678; ISS, n = 334; and MPHD, n = 272. After two years’ GH treatment, change in height standard deviation score (SDS) was +1.03 in SGA and +0.84 in ISS vs. +0.97 in IGHD (<it>p =</it> 0.047; <it>p <</it> 0.001 vs. IGHD, respectively). Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all <it>p</it> < 0.001).</p> <p>Conclusions</p> <p>After two years’ GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age). Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes.</p