Journal of Children's Orthopaedics vol:1 issue:2 pages:143-150
Purpose Greig cephalopolysyndactyly (GCPS) (OMIM
175700), a rare autosomal dominant disorder, is characterized
by a distinct combination of craniofacial, hand and
foot malformations. The hand and foot malformations often
require orthopedic assessment and treatment. The disorder
is caused by point mutations or deletions in the GLI3 gene,
located on chromosome 7p14.3. Herewith, we review the
hand and foot malformations in a cohort of 13 patients
referred for genetic testing.
Methods We reviewed the medical files of 13 patients
with GCPS seen at the Center for Human Genetics in
Leuven between 2003 and 2005. Clinical, molecular and
radiological findings, when available, were recorded.
Results We identified six different point mutations in the
GLI3 gene, two microdeletions and three larger chromosomal
deletions. In the hands, preaxial polydactyly was
never observed, but the malformations included postaxial
polydactyly, broad thumbs, clinodactyly of the thumbs and
various degrees of syndactyly. In the feet the spectrum of
malformations included preaxial polydactyly, postaxial
polydactyly, different degrees of syndactyly and broad
halluces. Syndactyly of the toes and hallux abnormalities
were present in all patients. Most frequently, syndactyly
was present between toes 1–2–3. The broadening of the
hallux was either due to a complete or partial duplication of
the first toe or to broadening of the distal phalanx. Mental
retardation was found in three cases and was associated
with a large chromosomal deletion of the GLI3 region.
Conclusion We found the classic hand and foot malformations
associated with GCPS in our cohort of patients.
Patients with a large chromosomal deletion had mental
retardation, but no structural brain anomalies were found.