Endocrine Abstracts

Introduction: The differential diagnosis of overgrowth includes constitutional tall stature, excess growth hormone (GH) and genetic syndromes. Sotos syndrome generally presents with overgrowth, dysmorphisms and early learning disabilities. Here in, we describe the diagnostic pathway of Sotos Syndrome in an adult male presenting with tall stature and mild morphological and cognitive features, prompted by his son’s clear manifestation of the classic triad.

Case report: A male child was born at term and delivered by c-section due to fetopelvic incompatibility, weighing 3460 g (z-score 0.2; percentile 59.1), measuring 52.5 cm (z-score 1.4; percentile 91.6), with a cephalic perimeter of 38.2 cm (z-score 2.9; percentile 99.8). Newborn hearing screening detected congenital conductive hearing loss. Since his 3 months, he has been above the 95th percentile for height and weight. Regarding family history, his father was 2006 cm (z-score 4.14; percentile 99.9) and had macrocephaly, elongated face and high forehead. He had refused medical investigation as he always had normal psychomotor development and no clinical symptoms. He concluded high school and works in dust separation. Laboratory study of the son, including IGF-1 and IGFBP-3, was normal. At 18 months, cranial and pituitary CT scans showed only an arachnoid cyst. At 2 years and 6 months, left wrist radiography revealed advanced bone age of 3 years and 6 months. An abdominal echography did not identify any organomegaly or abdominal mass. Genetic karyotype and Fragile X Messenger Ribonucleoprotein (FMR1) gene analysis were normal. Psychomotor retardation was noticed, mainly since he was 3 years old, predominantly in oral communication, locomotor skills and personal-social functions, displaying some autistic-like behaviors. Some dysmorphic features also became evident, such as dolichocephaly, high forehead and ogive palate. Sotos Syndrome was hypothesized and confirmed by identification of a heterozygous variant in Nuclear receptor binding SET Domain Protein 1 (NSD1) gene - c.6604T>C p. (Cys2202Arg). His father was also heterozygotic for this variant. Currently, the child is 9 years old, heights 157.9 cm (z-score 3.72; percentile 99.9) and weighs 39 kg (z-score 1.37; percentile 91.47). He attends the 3rd year of primary school. Cardiac anomalies were excluded.

Conclusion: Sotos Syndrome may mimic gigantism when intellectual and social impairment are mild. Therefore, it should be considered while approaching overgrowth without GH excess. Recognizing Sotos Syndrome is essential for appropriate surveillance due to increased risk of certain tumors and cardiac and renal anomalies, and for providing genetic counseling.