ESPE Abstracts (2022) 95 P1-232

1Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy; 2Dipartimento di Scienze della Sanità Pubblica e Pediatriche, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy; 3Genetica Medica, Università degli studi di Messina, Messina, Italy

Pseudohypoparathyroidism (PHP) is an hereditary disorder characterized by resistance to parathyroid hormone (PTH) and in varying degrees to TSH, GHRH and FSH/LH, and caused by loss-of-function mutations in the GNAS gene, encoding the membrane protein Gs-alpha. Pathognomonic of these patients is a dysmorphic phenotype, called Albright's Osteodystrophy, which includes short stature, obesity, round face, mental delay, subcutaneous ossifications and brachydactyly. The most frequent subtype is PHP 1A, caused by maternal segregated mutations. The aim of our report is to describe, starting from the case of three sisters, the enormous phenotypic variability of this pathology. Three sisters came to our observation for hyperparathyroidism and hypothyroidism. The oldest, met at the age of 4, presented hypocalcemia, hyperparathyroidism, congenital hypothyroidism, mild psychomotor delay, brachydactyly, stature on the low normal limit (15°P), and moderate excess weight. The second, met at the age of 6, presented hyperphosphatemia, hyperparathyroidism, acquired hypothyroidism, brachydactyly, round face and moderate obesity. In the end, the youngest, met at the age of 1, was affected by congenital hypothyroidism, hyperparathyroidism, severe short stature (-2.9 SD), and moderate obesity. In the suspicion of PHP, a GNAS study was carried out, calcitriol was started and levothyroxine was continued, with monitoring of calcemia, phosphorus, PTH and thyroid hormones. The clinical exome study revealed heterozygous deletion in GNAS with maternal segregation (c.118_139 + 51del), never described in literature before, with consequent diagnosis of PHP 1A. Despite the identical genotype, the three patients, in addition to a different onset of disease from a clinical-auxological and biochemical-hormonal point of view, presented, during the follow-up, significantly different clinical course and complications. In fact, the older sister has, to date, only a short stature (-2.26 SD) and mild mental retardation; the second sister has a stature in the range but developed osteorarefactions and osteosclerosis of the hands and feet which required orthopedic management and in the end, the youngest, presents a remarkably early onset (before 2 years of age) of severe obesity, short stature and diffuse subcutaneous ossifications. These cases are emblematic because demonstrates how pseudohypoparathyroidism is a very heterogeneous pathology, with considerably different presentation, course and type of complications from patient to patient, even among close relatives with the same genotype. The study of the GNAS gene, which in our case has allowed us to identify a mutation with maternal segregation never described in literature before, is fundamental for the diagnostic confirmation and the consequent multidisciplinary management.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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