Acrocephalosyndactyly

A rare group of inherited congenital malformation disorders characterized by craniosynostosis and fusion or webbing of the fingers or toes, often with other associated manifestations.

Epidemiology

The exact prevalence and birth incidence of ACS syndromes are not known. Overall incidence of all forms of craniosynostosis is reported to be 1/2,000 to 1/2,500 live births, but only small minorities of these cases are syndromic and the ACS syndromes are only one of many that have craniosynostosis as a finding.

Clinical description

Acrocephalosyndactyly includes a number of syndromes with similar and sometimes overlapping clinical manifestations. All include single-suture or multisutural craniosynostosis with distinctive facial features, variable intellectual and developmental deficits, and variable forms of hand or foot abnormalities. The group includes Apert, Pfeiffer, Saethre-Chotzen, Jackson-Weiss, and Carpenter syndromes (see these terms).

Etiology

Mutations in the following genes have been found in ACS: FGFR1 (8p12), FGFR2 (10q25.3-q26), FGFR3 (4p16.3), and TWIST1 (7p21).

Genetic counseling

The pattern of inheritance in acrocephalosyndactyly syndromes is autosomal dominant but de novo gene mutations are very common, especially with more severe sub types. Genetic counseling is recommended.