Identification of a novel GNAS mutation in a family with pseudohypoparathyroidism type 1A.

BACKGROUND: Pseudohypoparathyroidism (PHP) is caused by loss-of-function mutations at the GNAS gene (as in the PHP type 1A; PHP1A), de novo or inherited at heterozygous state, or by epigenetic alterations at the GNAS locus (as in the PHP1B). The condition of PHP refers to a heterogeneous group of disorders that share common clinical and biological features of PTH resistance. Manifestations related to resistance to other hormones are also reported in many patients with PHP, in association with the phenotypic picture of Albright hereditary osteodystrophy characterized by short stature, round facies, subcutaneous ossifications, brachydactyly, mental retardation and, in some subtypes, obesity. The purpose of our study is to report a new mutation in the GNAS gene and to describe the significant phenotypic variability of three sisters with PHP1A bearing the same mutation. CASE PRESENTATION: We describe the cases of three sisters with PHP1A bearing the same mutation but characterized by a significantly different phenotypic picture at onset and during follow-up in terms of clinical features, auxological pattern and biochemical changes. Clinical exome sequencing revealed a never before described heterozygote mutation in the GNAS gene (NM_000516.5 c.118_139 + 51del) of autosomal dominant maternal transmission in the three siblings, confirming the diagnosis of PHP1A. CONCLUSIONS: This study reported on a novel mutation of GNAS gene and highlighted the clinical heterogeneity of PHP1A characterized by wide genotype-phenotype variability. The appropriate diagnosis has crucial implications for patient care and long-term multidisciplinary follow-up.

Growth Hormone Treatment to Final Height in Turner Syndrome: Systematic Review.

PURPOSE: Turner syndrome (TS) is the most common sex chromosomal abnormality found in female subjects. It is a result of a partial or complete loss of one of the X chromosomes. Short stature is a hallmark of TS. Attainment of adult height (AH) within the normal range for height within the general female population represents the usual long-term goal of growth hormone (GH) treatment. The aim of this systematic review was to understand the efficacy of GH therapy on AH of patients with TS. METHODS: The literature review yielded for analysis 9 articles published from 2010 to 2021. Using the data from this literature search, the goal was to answer 5 questions: (1) What is the efficacy of GH on AH of girls with TS?; (2) Is AH influenced by the age at initiation of GH treatment?; (3) What is the optimal dose of GH to improve AH?; (4) Can the timing of either spontaneous or induced puberty influence AH?; and (5) Can the karyotype influence AH in patients with TS? FINDINGS: GH therapy and adequate dose could enable patients with TS to achieve appropriate AH compared with the possible final height without therapy. The greatest increase in height during GH therapy occurs in the prepubertal years, and if therapy is continued to AH, there is no further increase. Furthermore, karyotype did not show a predictive value on height prognosis and did not affect the outcome of GH administration or the height gain in girls with TS. IMPLICATIONS: Even if GH therapy is safe, close monitoring is indicated and recommended. Further evidence is needed to understand what other parameters may influence AH in patients undergoing GH therapy.