Noncompaction cardiomyopathy screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Noncompaction cardiomyopathy is an inheritable disease, and if a family member is affected, consideration should be given to screening other family members. Symptoms may be quite variable in different family members. Recurrence occurs in about 40% of family members.

It is recommended that first degree relatives be screened by transthoracic echocardiography^[1].

Some highly specialized centers do offer genetic screening. Several potential genetic abnormalities have been identified:

• The gene that encodes for alpha-dystrobrevin^[2]. This is a dystrophin-associated protein which has been mapped to chromosome 18q12. The role of this protein is to preserve the structural integrity of the muscle membrane.
• An X-linked genetic defect which involves a mutation in the gene G4.5 (TAZ) of the Xq28 chromosome region (a gene which encodes for tafazzin), the same region of the chromosome involved in several myopathies with cardiac involvement are located. These include Barth syndrome^[3], Emery-Dreifuss muscular dystrophy, and myotubular myopathy. As a result, some patients with NCC may have features of Barth syndrome.
• Mutations of the ryanodine receptor 2 gene (RyR2) as has been seen in patients with arrhythmogenic right ventricular dysplasia.
• Deletions of the FKBP12 gene result in noncompaction in the mouse^[4].
• Knockout of the Peg1 gene has been associated with NCC in the mouse ^[5].
• LMNA mutations
• Abnormalities of transcription factors such as NKX2.5 and TBX5.
• Abnormalities of 11p15 as suggested in a GWAS analysis.
• 22q11 deletion
• Distal 5q deletion involving the CSX gene ^[6]