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Elsahy-Waters Syndrome

OMIM ID:

autosomal recessive

Elsahy-Waters Syndrome

Alternate Names

ESWS
brachioskeletogenital syndrome
BSG syndrome

Defective Genes

CDH11

Clinical Characteristics

Ocular Features

Structural anomalies of periocular tissues are common.  Hypertelorism, proptosis, and telecanthus may be striking.  Colobomas or clefts of the upper lid are frequently seen.  The eyebrows are bushy and synophyrs may be present across a broad nasal bridge.  Megalocornea, downslanting lid fissures, glaucoma and cataracts have also been reported but are uncommon.

Systemic Features

The skull has been described as brachycephalic.  The midface is flat due to maxillary hypoplasia. The lower jaw is prominent and some patients have mandibular prognathism.  A bifid uvula or partial clefting of the palate are common.  Low-set and posteriorly rotated ears have been reported as well.

 Both pectus excavatum and pectus carinatum have been described.  The teeth have dysplastic enamel and often have obliterated pulp chambers and dental cysts.  Their roots may be shortened and deformed and they are often lost early.  Vertebrae may have fusion of the spines, particularly in the cervical area.  A mixed type of hearing loss is common and some degree of intellectual disability is often evident, especially in older individuals.  Most males have some degree of hypospadias.  Cryptorchidism has been reported in one individual.

Brain imaging in one case revealed no abnormalities.

Genetics

Inheritance

This disorder results from biallelic mutations in the CDH11 gene (16q21).  The parents have been consanguineous in most reports and no vertical transmission has been documented making autosomal recessive the most likely pattern of inheritance.

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 for the general disorder has been reported.  Eyelid and palatal defects may be surgically repaired and assistive hearing devices may be of benefit.  Special education is also likely to be helpful.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

Elsahy–Waters syndrome is caused by biallelic mutations in CDH11

PubMedID: 29271567

Homozygous indel mutation in CDH11 as the probable cause of Elsahy–Waters syndrome

PubMedID: 28988429