Gene: NKX2-1
Protein: homeobox protein Nkx-2.1
Clinical characteristics:
- Benign hereditary chorea
- Childhood onset chorea, usually before age 5 years
- Delayed motor development
- Dysarthria and gait abnormalities may occur
- No dementia (in contrast to Huntington’s disease)
- Little or no progression beyond second decade of life
- Choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress
- Also known as brain-lung-thyroid syndrome
- Onset at birth
- Involuntary movements
- Neonatal respiratory distress and risk for recurrent respiratory infections
- Congenital hypothyroidism
- Global developmental delay
- Hypotonia, ataxia, and dysarthria may occur
- Both show variable expressivity between, and within, families
Inheritance pattern: Autosomal dominant
What this test can tell us:
Testing is performed by sequencing the entire coding region of NKX2-1. This will detect point mutations, small deletions, and small insertions. If no heterozygous sites are detected, copy number analysis will be performed to detect a whole gene deletion. Deletions of the entire NKX2-1 gene have been reported in affected individuals. Testing also includes copy number analysis to detect if whole or partial deletions exist in this gene.
NKX2-1 is the only gene known to be associated with these specific disorders. However, a negative test result does not rule out a genetic cause of early onset chorea or congenital hypothyroidism. There are other genes associated with other types of movement disorders, as well as disorders associated with congenital hypothyroidism.
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: 10 – 14 days
CPT codes and cost:
Proband: 83891 (x1) 83900 (x1) 83904 (x9) 83909 (x1) 83912 (x1) $550
Known mutation: 83891 (x1) 83898 (x2) 83904 (x2) 83912 (x1) $235