Early development of extensive acanthosis nigricans (AN) is a key feature in some patients who have hypochondroplasia (HCH) in association with FGFR3 mutations.
Crouzon syndrome with acanthosis nigricans (CAN) is caused by a mutation in the fibroblast growth factor receptor ( FGFR) 3 gene that presents clinically as Crouzonoid craniofacial features in association with other anomalies such as acanthosis nigricans and benign odontogenic tumors.
Familial acanthosis nigricans caused by the mutation of the fibroblast growth factor receptor 3 (FGFR3) gene is characterized by short stature, hypochondroplasia and acanthosis nigricans.
Besides the expansion of the phenotypic spectrum of FGFR3-related OCDs to HCH with AN, this observation underscores the continuing adverse effect of this specific mutation upon the normal inhibitory signaling of the receptor at least in epidermal cells.
Germline mutations of the FGF receptor 3 (FGFR3) cause autosomal dominant skeletal disorders such as achondroplasia and thanatophoric dysplasia, which can be associated with acanthosis nigricans of the skin.
Two other FGFRs, FGFR1 and FGFR3, also account for craniosynostoses of variable severity [Pfeiffer, Crouzon with acanthosis nigricans (a pre-malignant skin disorder), and Muenke syndromes].
Bilateral basilar venous atresia is most common in patients with the FGFR3ala391glu mutation and crouzonoid features with acanthosis nigricans, but may be found in patients with FGFR2 mutations.
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.