Familial acanthosis nigricans due to K650T FGFR3 mutation.

BACKGROUND Acanthosis nigricans is a feature of several syndromes caused by activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3), including Crouzon syndrome with acanthosis nigricans, thanatophoric dysplasia, and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN syndrome). OBSERVATIONS We describe a healthy 4-year-old African American girl with generalized acanthosis nigricans since infancy. Her father had a history of acanthosis nigricans since childhood, in addition to Crohn disease, obesity, and adult-onset diabetes mellitus. A pedigree with numerous affected family members was constructed. Other than slightly short stature, no associated anomalies were found, including dysmorphic features or skeletal or neurologic defects. Genetic testing revealed a previously undescribed, heterozygous lysine to threonine mutation at codon 650 of the FGFR3 gene in the 4 affected family members who were tested. CONCLUSION Extensive acanthosis nigricans in early childhood, especially with a family history of acanthosis nigricans, may warrant testing for FGFR3 mutations.