ESPE Abstracts (2019) 92 P1-194


1Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy. 2Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy. 3Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', Florence, Italy. 4Division of Pediatric Endocrinology, Meyer University Children's Hospital, University of Florence, Florence, Italy

The epidemic spread of obesity in children has triggered the commitment of scientific research, which has allowed us to understand its genetic basis; the different forms of genetic obesity share common clinical aspects, making it difficult to achieve a molecular diagnosis based only on our clinical suspicion. We report a female patient presented with neonatal hypotonia, hyperphagia and early onset excessive weight gain, strabismus and high hypermetropia. Regarding her neurodevelopment, she walked at 30 months and showed expressive language delay. The phenotype of our patient has evolved over the years with persistence of increasing obesity and onset of hepatic steatosis, hyperinsulinism and insulin resistance. PWS-AS test and array-CGH resulted normal. We performed whole-exome sequencing (WES) that disclosed a de novo missense mutation in PHF6, within the PHD-type 2 domain of the protein; X-inactivation analysis showed normal X-inactivation in blood lymphocytes. Mutations affecting the coding region of this gene or its splicing have been associated with Borjeson-Forssman-Lehmann syndrome (BFLS), an X-linked recessive disease, characterized by intellectual disability (ID), epilepsy, hypogonadism, hypometabolism, obesity. Female carriers usually not show any findings or present only mild symptoms. To date, although this condition is referred as an X-linked recessive, de novo aberrations in PHF6 were reported in 12 females with a variable phenotype, characterized by ID, characteristic facial features, fingers and dental anomalies, only partially overlapping with the male phenotype. Our case, once again, underlines how the X chromosome inactivation, different in different tissues, can produce variable clinical phenotypes related to the same condition, and that some disorders are not really transmitted as recessive. Furthermore, this situation further complicates the clinical picture of complex diseases, like early-onset genetic obesity forms. WES is a fundamental tool to identify causative variants, reducing time and costs of diagnosis and offering the opportunities for targeted management and therapy.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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