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Corpus Callosum Agenesis with Facial Anomalies and Cerebellar Ataxia

Corpus Callosum Agenesis with Facial Anomalies and Cerebellar Ataxia

Patient Information

Characteristics

Background and History

This is a severe heritable neurological condition with facial anomalies and slow development secondary to brain deformities.

Clinical Correlations

Infants are born with small heads (microcephaly) and their muscles seem stiff which may lessen later.  Excessive hair (hirsutism) is generally present with a low hairline in the front, bushy eyebrows, and long eyelashes.  The eyelids appear puffy. The ears protrude, are lower than normal, and often rotated towards the back of the head.  The lower lip seems to protrude while the nose openings point forward.  Uncoordinated hand movements and a general unsteadiness (ataxia) are usually present.  Brain imaging reveals structural malformations.  Speech is poor or never develops and cognitive functioning is poor.  Physical growth is slow.  

Genetics

Inheritance

This is an autosomal recessive condition caused by mutations in a pair of specific genes.  Parents who usually carry only one mutation are clinically normal but the offspring of two such parents each inherit a 25% risk of having this condition.

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.

Diagnosis and Prognosis

The physical anomalies should suggest the diagnosis at birth while many of the neurological deficits become evident as children grow.  Pediatricians and neurologists are likely to collaborate in the diagnosis and follow-up.  Nothing is known regarding longevity but patients have severe physical limitations and may require a wheelchair for locomotion.

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