Endocrine Abstracts

JOINT3995

Floating-Harbor syndrome (FHS) is an extremely rare autosomal dominant genetic disorder with specific features, including facial dysmorphia, skeletal abnormalities (delayed bone age), and intellectual, speech, and systemic impairments. It is caused by mutations in the SNF-2-related CREBBP activator protein (SRCAP) gene. As of 2021, over 100 cases of FHS have been reported globally, with the first case described in 1973. Hyperphagia is not typical and GH treatment has limited effects on short stature in FHS. Clinical case: Patient E., 39 years old, presented with complaints of obesity that is difficult to manage and increased appetite. Her medical history indicates that she was born following a normal pregnancy and had normal weight and growth parameters at birth. Neonatal hypotonia was absent, and the sucking reflex was normal. However, from an early age, she exhibited delays of growth, intellectual and speech development, learning difficulties, bilateral sensorineural hearing loss, hyperphagia, and progressive weight gain. She received no GH treatment. Notably, she showed persistent obsessions related to food-seeking behavior. At the age of 25, Prader-Willi syndrome was suspected, but no molecular genetic testing was performed. She also underwent surgery for a paraovarian cyst and cholelithiasis. At the age of 37 she suffered an acute ischemic stroke. Upon examination, notable phenotypic features were observed: acromicria, microcephaly, short stature (height 150 cm, weight 92 kg), broad deep-set eyes, a large bulbous nose, short neck, clinodactyly V and a cleft upper lip. No respiratory disturbances, sleep apnea, IGF1 or thyroid test abnormalities were revealed. Impaired glucose tolerance, mild liver enzymes elevation due to NAFLD and hyperuricemia were identified. Given the absence of convincing data characteristic of Prader-Willi syndrome, along with the unclear clinical picture, patient history, and her phenotypic characteristics, FHS was suspected. This diagnosis was confirmed by genetics - whole-exome sequencing, which revealed a heterozygous variant in the SRCAP gene (c.7330C>T). Following treatment with GLP-1 agonists, the patient experienced a reduction in body mass by 13% from baseline, with control of glucose metabolism and other metabolic disturbances and hyperphagia reduction.

Conclusion: A diagnosis of FHS is suspected when typical clinical findings are present and can be confirmed through SRCAP gene sequencing. We report a late diagnosis case masked by a hyperphagia leading to morbid obesity, although it is treatable with GLP-1-analoges. It is important to remember that obesity is not only a symptom but also a potential indicator of complex genetic disorders.