Endocrine Abstracts

JOINT2836

Objective: To delineate the chronological progression and pathophysiological effects of MAGEL2 mutations in infants with Schaaf-Yang syndrome, focusing on associated endocrine disorders and developmental dysfunctions such and characteristic dysmorphisms.

Methods: A detailed review of clinical, hormonal, and genetic data from two infants with Schaaf-Yang syndrome, including the onset of specific endocrine characteritics and developmental features, particularly those related to MAGEL2 mutations.

Results: AVP-D Both infants presented with symptoms of arginine vasopressin deficiency (AVP-D) such as hypernatremia and polyuria from the neonatal period, highlighting disturbances in hypothalamic function. Hypopituitarism: Manifestations of growth hormone deficiency and transient adrenal insufficiency were noted early in life, typically emerging within the first few months. Delayed Hyperinsulinism: Diagnosis of hyperinsulinism occurred at seven and eleven months, managed with diazoxide and octreotide, reflecting progressive pancreatic beta-celldysfunction. Genetic Insights: Infants displayed de novo truncatingmutations in the MAGEL2 gene (c.1996dup and c.1912C>T), which correlate with more severe phenotypic manifestations. Developmental Dysmorphisms: Both infants exhibited characteristic facial features (broad forehead, almond-shaped eyes, flattened nasal bridge, thin upper lip) and finger contractures associated with oligohydramnios, highlighting the prenatal impact of MAGEL2 mutations.

Conclusion: The profound endocrine and developmental manifestations in Schaaf-Yang syndrome underscore the criticalrole of MAGEL2 mutations in disrupting hypothalamic functions. These mutations not only impair hormone regulation leading to AVP-D, hypopitutarism and hyperinsulinism but also affect prenatal development, contributing to distinct facial dysmorphisms and contractures. This detailed understanding is crucial for developing targeted interventions and managing the complex endocrine dysfunctions in SYS, facilitating improved outcomes through proactive and informed therapeutic strategies.