FAM126A

Cataracts, Congenital, and Hypomyelinating Leukodystrophy

Clinical Characteristics
Ocular Features: 

Bilateral cataracts may be present at birth or later in the first decade of life.  The ERG and flash VEPs are normal.

Systemic Features: 

Psychomotor development is initially normal but signs of delay are usually present during the first year of life.  Patients may be able to walk but only with support.  Pyramidal and cerebellar dysfunction, muscle weakness and wasting, dysarthria, truncal hypotonia, intention tremor, and spasticity are evident during the first decade.  Some have seizures.  Cognitive impairment ranges from mild to moderate.  Most patients become wheelchair-bound late in the first decade of life and some do not survive beyond childhood.

Hypomyelination and mild axonal loss may be seen in peripheral nerve biopsies while neuroimaging shows evidence of diffuse and progressive cerebral white matter atrophy.

Genetics

This is an autosomal recessive disorder caused by homozygous mutations in FAM126A (7p15.3) leading to a deficiency of the neuronal protein hyccin.  The result is deficient myelination in both central and peripheral nervous systems.  No symptoms are evident in heterozygotes.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

The cataracts may be surgically removed.  There is no known treatment for the progressive neurologic deterioration but physical therapy and special education may be helpful.

References
Article Title: 

Novel FAM126A mutations in Hypomyelination and Congenital Cataract disease

Traverso M, Assereto S, Gazzerro E, Savasta S, Abdalla EM, Rossi A, Baldassari S, Fruscione F, Ruffinazzi G, Fassad MR, El Beheiry A, Minetti C, Zara F, Biancheri R. Novel FAM126A mutations in Hypomyelination and Congenital Cataract disease. Biochem Biophys Res Commun. 2013 Aug 30. [Epub ahead of print] PubMed PMID: 23998934.

PubMed ID: 
23998934

Phenotypic characterization of hypomyelination and congenital cataract

Biancheri R, Zara F, Bruno C, Rossi A, Bordo L, Gazzerro E, Sotgia F, Pedemonte M, Scapolan S, Bado M, Uziel G, Bugiani M, Lamba LD, Costa V, Schenone A, Rozemuller AJ, Tortori-Donati P, Lisanti MP, van der Knaap MS, Minetti C. Phenotypic characterization of hypomyelination and congenital cataract. Ann Neurol. 2007 Aug;62(2):121-7.

PubMed ID: 
17683097
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