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Cole-Carpenter Syndrome 2

OMIM ID:

autosomal recessive

Cole-Carpenter Syndrome 2

Alternate Names

CLCRP2

Defective Genes

SEC24D

Clinical Characteristics

Ocular Features

Postnatally the eyes are prominent and hypertelorism has been reported.  The palpebral fissures slant downward and the root of the nose is angular. 

Systemic Features

This is primarily a skeletal disorder with impaired skull ossification and multiple bone fractures of prenatal origin.  It is sometimes confused with forms of osteogenesis imperfecta.  The skull is poorly ossified and frequent diaphyseal fractures of the long bones occur leading to motor delays and short stature.  Rib fractures are sometimes seen. Intelligence seems to be normal.  A receding chin has been noted and the hard palate is highly vaulted.  The midface is flat.

Genetics

Inheritance

This disorder results from compound heterozygous mutations in the SEC24D gene (4q26).  Only a few patients have been reported.

For a somewhat similar but autosomal dominant disorder see Cole-Carpenter Syndrome 1 (112240).

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.

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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

Physical activity should be restricted to noncontact sports and where the cranium has ossification defects a helmet should be worn.  Fractures should be appropriately treated.

Selected Resources

Web Resources

Publications

Displaying 1 - 1 of 1

Mutations in SEC24D, Encoding a Component of the COPII Machinery, Cause a Syndromic Form of Osteogenesis Imperfecta

PubMedID: 25683121