Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Crouzon Syndrome (Craniofacial Dysostosis Type I, CFD1) [Q75.1]

OMIM numbers: 123500, 176943 (FGFR2), 612247, 134934 (FGFR3)

Dr. med. Imma Rost, Dipl.-Biol. Christina Sofeso

Scientific Background

Crouzon syndrome occurs with a frequency of 1 in 63,000 and constitutes about 5% of all craniosynostoses. Usually the coronal suture is affected, sometimes in combination with further sutural synostoses. This often leads to brachycephaly. The short anterior cranial fossa results in exophthalmos, often with a divergent strabismus. Visual acuity can be impaired. Midface hypoplasia with a prominent nose and relative mandibular prognathism is characteristic. Cervical spine fusions occur in approx. 30% of all patients and slight hearing impairment is reported in up to 50%. Hands and feet do not show malformations. Intelligence generally lies within the normal range. 

Crouzon syndrome is caused by mutations in the FGFR2 gene and occurs in approx. 50 % of all cases sporadically and in approx. 50 % familial. In sporadic cases mutations are only found on the paternal allele which indicates a strong paternal age effect as in Apert syndrome. So far, there are only surgical therapeutic options available. A special form is Crouzon syndrome with acanthosis nigricans which is caused by a Ala391Glu mutation in FGFR3.