Fusion of two fingers or two toes or the presence of a tab of skin representing an extra digit may be seen at birth in an otherwise normal individual. However, when syndactylism is more severe and is accompanied by premature closure of cranial sutures, the nervous system usually proves to be abnormal as well. The general term acrocephalosyndactyly is used to describe the several combinations of craniosynostotic and facial deformities and fusion of digits. Several of these disorders are a consequence of mutations in genes encoding one of two fibroblast growth factors or proteins related to them. The following descriptions include only the major features; most have, in addition, distinctive malformations of the orbits, ears, and palate.
1. Acrocephalosyndactyly types I and II (typical and atypical Apert syndrome). Turribrachycephalic skull, syndactyly of hands and feet (“mitten hands,” “sock feet”), moderate to severe mental retardation.
2. Acrocephalosyndactyly III (Saethre-Chotzen syndrome). Various types of craniosynostoses, proximally fused and shortened digits, moderate degree of mental retardation. Transmission as an autosomal dominant trait.
3. Acrocephalosyndactyly IV (Pfeiffer syndrome). Turribrachycephaly; broad, enlarged thumbs and great toes; partially flexed elbows (radiohumeral or radioulnar synostoses); mild and variable cognitive impairment; autosomal dominant inheritance.
4. Acrocephalopolysyndactyly V (Carpenter syndrome). Premature fusion of all cranial sutures with acrocephaly, flat bridge of nose, medial canthi displaced laterally, excess digits and syndactyly, cognitive impairment.
5. Acrocephalosyndactyly with absent digits. High, bitemporally flattened head; absent toes and syndactylic fingers; moderate cognitive impairment.
6. Acrocephaly with cleft lip and palate, radial aplasia, and absent digits. Microbrachycephaly because of craniostenosis, cleft lip and palate, absent radial bones, severe cognitive impairment.
7. Dyschondroplasia, facial anomalies, and polysyndactyly. Keel-shaped skull and ridge through center of forehead (metopic suture), short arms and legs, postaxial polydactyly and short digits, moderate cognitive impairment.
In all the foregoing types of syndactylism and cranial abnormalities, which may be regarded as variants of a common syndrome, the diagnosis can be made at a glance because of the deformed head, protuberant eyes, and abnormal hands and feet. The degree of cognitive delay proves to be variable, usually moderate to severe, but occasionally cognition is normal or nearly so. The brain has been examined in only a few instances and not in a fashion to display fully the type and extent of this developmental abnormality.
Members of this group have distinctive anomalies of the cranium, face, and other parts, but craniosynostosis is not a consistent feature.
1. Craniofacial dysostosis (Crouzon syndrome). Variable degrees of craniosynostosis; broad forehead with prominence in the region of the anterior fontanel region; shallow orbits with proptosis; midline facial hypoplasia and short upper lip; malformed auditory canals and ears; high, narrow palate; moderate mental retardation. As noted above, a genetic defect in one of the fibroblast growth factor receptors is responsible for about one-third of cases that are not associated with other deformities (Moloney et al). Autosomal dominant inheritance is seen in most cases.