Adult presentation of Simpson-Golabi-Behmel syndrome due to a hemizygous GPC3 stopgain variant mimicking acromegaly.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare, X-linked overgrowth disorder caused by pathogenic variants in the GPC3 gene, which encodes glypican-3. It is characterized by prenatal and postnatal overgrowth, craniofacial dysmorphism, supernumerary nipples, skeletal anomalies, and variable neurodevelopmental delay. Because of overlapping features such as macroglossia and coarse facial appearance, SGBS may be mistaken for acromegaly. We report a 33-year-old man evaluated for apparent acromegaloid facies. He had tall stature (196.5 cm; >97th percentile), macroglossia, mandibular prognathism, hypertelorism, supernumerary nipples, delayed developmental milestones, and mild intellectual disability. His brother had similar but milder features. Serum insulin-like growth factor 1 concentration was 75.9 ng/mL (SI: 9.95 nmol/L) (reference range, 94-284 ng/mL [SI: 12.3-37.2 nmol/L]), and growth hormone suppressed to 0.49 ng/mL (SI: 0.49 µg/L) following an oral glucose tolerance test, excluding acromegaly. Magnetic resonance imaging showed a 2.2-mm pituitary microadenoma considered incidental. Exome sequencing identified a hemizygous nonsense pathogenic variant in GPC3 (c.1159C > T; p.Arg387Ter), confirming SGBS type 1; the mother was heterozygous. This case highlights that tall stature with dysmorphic features, and supernumerary nipples, should prompt consideration of SGBS, with endocrine testing used to exclude acromegaly.