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Carpenter Syndrome

OMIM ID:

autosomal recessive

Carpenter Syndrome

Alternate Names

acrocephalopolysyndactyly type II
ACPS II

Defective Genes

RAB23

Clinical Characteristics

Ocular Features

A variety of ocular anomalies have been reported in Carpenter syndrome with none being constant or characteristic.  The inner canthi are often spaced widely apart and many have epicanthal folds and a flat nasal bridge.  Other reported abnormalities are nystagmus, foveal hypoplasia, corneal malformations including microcornea, corneal opacity, and mild optic atrophy and features of pseudopapilledema.

Systemic Features

Premature synostosis involves numerous cranial sutures with the sagittal suture commonly involved causing acrocephaly (tower skull).  Asymmetry of the skull and a ‘cloverleaf’ deformity are often present.  The polydactyly is preaxial and some degree of syndactyly is common especially in the toes.  The digits are often short and may be missing phalanges.  Some patients are short in stature.  Structural brain defects may be widespread including atrophy of the cortex and cerebellar vermis.  Septal defects in the heart are found in about one-third of patients.  The ears can be low-set and preauricular pits may be seen.  Some but not all patients have obesity and a degree of mental retardation.

Genetics

Inheritance

This is an autosomal recessive syndrome caused by a mutation in the RAB23 gene (6p12.1-q12).

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

No treatment of the ocular defects is necessary in most cases. Craniectomy may be required in cases with severe synostosis.

Selected Resources

Publications

Displaying 1 - 3 of 3

Carpenter Syndrome

PubMedID: 19165041

Carpenter’s syndrome: Acrocephalopolysyndactyly. An autosomal recessive syndrome

PubMedID: 5935752

RAB23 Mutations in Carpenter Syndrome Imply an Unexpected Role for Hedgehog Signaling in Cranial-Suture Development and Obesity

PubMedID: 17503333