We report here the identification of a mutation in the transmembrane region of FGFR3, common to three unrelated patients with classical Crouzon syndrome and acanthosis nigricans, a dermatological condition associated with thickening and abnormal pigmentation of the skin.
Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.
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.
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].
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.
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.
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.