SAT-223 Endocrinopathies Associated with Wolf-Hirschhorn Syndrome

Abstract Disclosure: X. Xu: None. A.E. Balazs: None. Objective: To review the endocrine disorders in patients with Wolf-Hirschhorn syndrome. Background: Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by a partial deletion of the short arm of chromosome 4. NSD2, LETM1, and MSX1 are the genes that are deleted in people with the typical signs and symptoms of this disorder. Proteins produced from the NSD2 gene function as histone methyltransferases, which regulate the activity of other genes. The NSD2 gene proteins are involved in embryonic development, body growth and other biological processes. LETM1 protein may be involved in the transport of charged calcium ions across membranes within mitochondria. While growth retardation is a hallmark feature, the full spectrum of associated endocrinopathies remains poorly defined. Existing literature is limited to isolated reports of hyperparathyroidism and diabetes mellitus following acute pancreatitis. Methods: Retrospective chart review. Results: Between 2012 and 2024, 37 patients with WHS were assessed at our institution. The cohort included 16 males and 21 females, ranging in age from 6 months to 28 years. Of these, five had normal height, 32 exhibited short stature. Hypothyroidism with negative antibodies was identified in one female patient, who also had premature thelarche. Three additional patients were evaluated for precocious puberty: one was diagnosed with non-classic congenital adrenal hyperplasia, one received gonadotropin-releasing hormone agonist therapy for central precocious puberty, and one had premature pubarche without hormonal abnormalities. Two patients presented with hypercalcemia: one attributed to primary hyperparathyroidism, and the other secondary to chronic kidney disease. The latter patient subsequently developed diabetes at age 19, with negative islet antibody. Transient hyperinsulinemia, likely secondary to intrauterine growth restriction, was observed in one patient, who passed a safety fasting test after discontinuing diazoxide. Two patients presented with hyponatremia: one with features of mineralocorticoid deficiency, including hyperkalemia, metabolic acidosis, and elevated plasma renin of 148.65 ng/ml/hr, alongside aldosterone level of 34 ng/ml; the other with central adrenal insufficiency with normokalemia, hypochloremia, and alkalosis. Conclusion: These findings underscore the wide range of endocrine abnormalities in WHS, including growth disorders, hypothyroidism, hyperparathyroidism, precocious puberty, and adrenal insufficiencies. Comprehensive evaluation and management are essential to address the complex needs of individuals with WHS. Presentation: Saturday, July 12, 2025