Abstract:

Objective: To analyze the correlation between clinical phenotype and genotype in a patients presenting with Crouzon-like facial appearance, disproportionate short stature and acanthosis nigricans (AN) caused by fibroblast growth factor receptor 3 gene（FGFR3） mutation. Methods: The 13-year-old boy presented craniofacial dysmorphic features, with disproportionate short stature and severe acanthosis nigricans. The clinical data was retrieved and the laboratory parameters of glucose and lipid metabolism, and endocrine hormone were acquired. The results of skin pathology and bone X-ray exami-nation were analyzed. The DNA sample was extracted from peripheral blood withdrawn from the proband and family members for whole-exome sequencing (WES) and Sanger sequencing. Results: Laboratory examination revealed normal hormone level and slight insulin resistance without hyperglycemia. Skeletal survey showed no evidence of midface hypoplasia, brachycephaly or achondroplasia. Skin biopsy identified cutaneous papillomatosis consistent with the manifestations of AN. A spontaneous mutation (NM_00142: c.742C>T; Chr4: 1803564; p. R248C) was identified in FGFR3 by whole-exome sequen-cing, a causative gene established by American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusions: The report described for the first time a case presenting Crouzon-like facial appearance with mild skeletal dysplasia and progressive acanthosis nigricans caused by classical R248C mutation in FGFR3. Sequencing of FGFR3 should be consi-dered in patients with short stature or subtle dysmorphic features, especially accompanied by signs of early onset AN.

Key words: Crouzon-like syndrome, Acanthosis nigricans, Development delay, Fibroblast growth factor receptor 3 gene