Acanthosis nigricans in a Japanese boy with hypochondroplasia due to a K650T mutation in FGFR3

Hypochondroplasia (HCH) is an autosomal dominant form of skeletal dysplasia and shares several phenotypic features with achondroplasia (ACH), including a disproportionately short stature, shortened limbs, lumbar lordosis, macrocephaly, and facial dysmorphism, etc. However, these features are less obvious than those of ACH, which often makes it difficult to make a definitive diagnosis for HCH, especially until early childhood (1). For these reasons, HCH is usually diagnosed later in childhood when the patient’s short stature has become more obvious. Acanthosis nigricans (AN) involves velvety and pigmented (brown) hyperkeratosis of the skin. It is usually found in bodily folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, forehead, and other areas. AN is commonly observed in children with severe obesity and type 2 diabetes (2, 3). In addition, it is an important clinical feature of more severe forms of skeletal dysplasia than HCH, including ACH, thanatophoric dysplasia (TD), and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) (4, 5). However, AN has occasionally been reported in patients with HCH. Mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) are known to cause skeletal dysplasia, including ACH, HCH, TD, and SADDAN, and FGFR3 gene analysis allows for the early diagnosis of such conditions (6). Various mutations have been identified in codon 650 of FGFR3, including K650N and K650Q in HCH (7), K650M in TD1 and SADDAN, and K650E in TD2 (5). We report the case of a Japanese boy who developed AN coexisting with a mild height deficit, which prompted us to perform an FGFR3 mutation analysis. A K650T missense mutation was identified. To the best of our knowledge, this is the third reported case of HCH combined with AN due to a K650T mutation in FGFR3.