Variants of STAR, AMH and ZFPM2/FOG2 May Contribute towards the Broad Phenotype Observed in 46,XY DSD Patients with Heterozygous Variants of NR5A1.

Variants of NR5A1 are often found in individuals with 46,XY disorders of sex development (DSD) and manifest with a very broad spectrum of clinical characteristics and variable sex hormone levels. Such complex phenotypic expression can be due to the inheritance of additional genetic hits in DSD-associated genes that modify sex determination, differentiation and organ function in patients with heterozygous NR5A1 variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the NR5A1 gene. We tested the transactivation activity of novel NR5A1 variants. We additionally included six of these patients in a targeted diagnostic gene panel for DSD and identified a second genetic hit in known DSD-causing genes STAR, AMH and ZFPM2/FOG2 in three individuals. Our study increases the number of NR5A1 variants related to 46,XY DSD and supports the hypothesis that a digenic mode of inheritance may contribute towards the broad spectrum of phenotypes observed in individuals with a heterozygous NR5A1 variation.

[Recommendations for the diagnosis and follow up of the foetus and newborn child born to mothers with autoimmune thyroid disease]. / Recomendaciones para el diagnóstico y seguimiento del feto y del recién nacido hijo de madre con patología tiroidea autoinmune.

The objective of this document is to review the current recommendations in the management of the foetus and the newborn child born to mothers with autoimmune thyroid disease. In 2017, the American Thyroid Association published guidelines for the diagnosis and management of thyroid disease during pregnancy and post-partum. In this guide, 97 recommendations were made, and an algorithm for the diagnosis and treatment of gestational hypothyroidism was proposed. Also, in this last year, a wide review was been published on the foetal and neonatal approach of the child of a mother with Graves' disease. The importance of the determination of maternal antibodies against thyrotropin receptor in the second half of pregnancy is stressed, in order to adequately stratify the risk in the neonate.

[Growth hormone treatment in small for gestational age children in Spain]. / Tratamiento con hormona de crecimiento en pequeños para la edad gestacional en España.

INTRODUCTION: Since its approval by the European Medicines Agency, a great number of patients born small for gestational date have received recombinant growth hormone treatment in Spain. The aim of this study is to analyse its outcome in the setting of ordinary clinical practice. METHODS: Information was gathered from the registers of the assessment boards that authorise all growth hormone treatments prescribed in public hospitals in six autonomic communities (regions). RESULTS: Valid data from 974 patients was obtained. All of them complied with criteria established by the European Medicines Agency. Patients in the sample were smaller in length than weight at birth, with their median target height being below 1 standard deviation (SD), and 23% of them had been delivered prematurely. Treatment was started at 7.2±2.8 years (mean±SD). The mean patient height at start was -3.1±0.8 SD. They gained 0.7±0.2 SD in the first year, and 1.2±0.8 SD after two years. Final height was attained by 8% of the sample, reaching -1.4±0.7 SD. CONCLUSIONS: These results are similar to other Spanish and international published studies, and are representative of the current practice in Spain. Despite treatment being started at a late age, adequate growth is observed in the short term and in the final height. Up to a 24% of patients show a poor response in the first year.