Hypomyelination and Congenital Cataract

Gene: FAM126A (also known as DRCTNNB1A)

Protein: hyccin

Clinical characteristics:

• Bilateral congenital cataracts
• Normal psychomotor development in first year of life
• Progressive ataxia and spasticity
• Mild to moderate cognitive impairment
• Hypotonia
• Dysarthria
• Truncal titubation and intention tremor
• Peripheral neuropathy
• Progressive scoliosis
• Characteristic MRI findings
  • Diffusely abnormal supratentorial white matter
  • Sparing of the cortical and deep gray matter structures
  • Hypomyelination of supratentorial white matter +/- deep cerebellar white matter
  • Increased white matter water content
  • White matter bulk loss and gliosis in older individuals

Inheritance pattern:  Autosomal recessive

What this test can tell us:
Testing is performed by sequencing the entire coding region and intron-exon junctions of FAM126A. This assay will detect point mutations, small deletions, and small insertions. It will not detect a partial or whole gene deletion or duplication.

A negative test does not rule out a genetic cause of a neurologic disorder. There are many other genes associated with different types of neurologic disorders and leukodystrophies. Pelizaeus-Merzbacher Disease (PMD) is an X-linked disorder caused by mutations in the PLP1 gene. Testing for PMD is available in our laboratory and can be performed if clinically indicated.  Mutations of the GJC2 gene cause an autosomal recessive syndrome known as Pelizaeus-Merzbacher-Like Disease (PMLD) or hypomyelinating leukodystrophy-2 (HLD2). Testing for PMLD is also available in our laboratory and can be performed if clinically indicated.

Sample requirements: Draw one or two 4-cc tubes of blood in EDTA/purple-top tube (minimum of 1-2 cc for infants).

Turn-around time:   4-6 weeks

CPT codes and cost:
83891 x 1    83898 x 12    83894 x 1    83904 x 24     83912 x 1    $1131

Hypomyelination and Congenital Cataract Testing Packet

Helpful Internet Resources

• GeneReview
• OMIM Entries