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Cataracts, Congenital, Intellectual Disability, Abnormal Striatum, and ADHD

autosomal recessive

Cataracts, Congenital, Intellectual Disability, Abnormal Striatum, and ADHD

Defective Genes

KCNA4

Clinical Characteristics

Ocular Features

Cataracts (not further described) were described as congenital although the diagnosis was usually made early in the first decade of life.  One patient was diagnosed at the age of 8 years with glaucoma and a cloudy cornea of the left eye.  Another patient had cataract surgery.  Visual acuities have not been reported.

Systemic Features

Four members of a consanguineous Saudi family have been reported with growth and mental retardation, microcephaly, dystonia, and spasticity.  IQs in the range of 77-89 were reported.  Linguistic delay is common.  Dysarthria and decreased cognitive function are present.  MRIs revealed thinning of the lentiform nucleus and swelling of the caudate heads.  

Genetics

Inheritance

Homozygous mutations in the KCNA4 (11p14.1) (176266) gene are responsible for this disorder.

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

No treatment is available for the general condition.  Cataract surgery may be considered.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

A novel syndrome of abnormal striatum and congenital cataract: evidence for linkage to chromosomes 11

PubMedID: 23181898

KCNA4 deficiency leads to a syndrome of abnormal striatum, congenital cataract and intellectual disability

PubMedID: 27582084