ESPE Abstracts

Objective: Acanthosis nigricans (AN) is characterized by velvety and papillomatous pigmented hyperkeratosis of the flexures and neck. Mutations in fibroblast growth factor receptor 3 (FGFR3) gene have been identified as one of the causes of skeletal dysplasia with AN. However, there have been few reports about familial AN with hypochondroplasia. Here we report a familial case with FGFR3 gene mutation.

Case reports: A 16-year-old boy with no significant past medical history was referred to our institution because of short stature. He was born at term by spontaneous vaginal delivery and his birth weight was 3370g. His height, weight, and BMI were 139.10 cm (SDS -2.74), 3.06 kg (SDS -1.39) and 18.76 (SDS -0.06), respectively. His testicular volume was 4.0 ml and Tanner stage I for pubic hair. His bone age was estimated to be 10.5 years old (SDS -0.55) based on Greulich-Pyle method. The patient presented relative macrocephaly and upper-to-lower body-segment ratio (1.4) indicated abnormal body proportion. In the developmental state, there was no intellectual disability but poor growth. He presented hyperpigmentation with a velvety texture, which could be suspected as acanthosis nigricans on the neck, axilla, trunk and abdomen. Acanthosis nigricans was confirmed by histopathological study of a 4mm punch biopsy from the abdominal region. Fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) were within normal range. The growth hormone stimulation test induced by insulin and arginine showed a growth hormone peak of 14.57 ng/ml. The characteristics of short stature and generalized hyperpigmentation were observed not only in the patients but also in the mother and grandfather. Genetic studies for hypochondroplasia using genomic DNA extracted from peripheral lymphocytes was conducted, and the genetic tests confirmed the presence of a mutation in the FGFR3 mutation. The proband had a heterozygous mutation of c.1949delinsTTCT, which lead to the p.[(Lys650Ile;Lys650_Thr651insLeu)] mutation at the protein level. The same mutation was detected in a heterozygous state in the mother and grandfather.

Conclusion: We describe a family with AN caused by an autosomal dominant mutation in the FGFR3 gene. Therefore, the mutations of FGFR3 should be taken into consideration in patients with AN accompanying hypochondroplasia.