Congenital fibre type disproportion and non-compaction cardiomyopathy associated with insulin resistance

We present new data about a patient affected by congenital fibre type disproportion (CFTD) and non-compaction cardiomyopathy (NC), who was preliminarily reported in the 2007 edition of the WMS congress. This female newborn was the first child of healthy parents with an history of consanguinity and diabetes mellitus in the maternal line. At birth she presented with poor sucking, hypoglycemia, congenital dislocation of the hip and mild hypotonia. At age 17 months a muscle biopsy revealed a picture of CFTD whereas cardiological evaluation (standard echocardiography and MRI) led to NC diagnosis. Periodical controls showed slowly progressive clinical picture characterized by: limb-girdle like myopathy (nonetheless serum CK levels remained always in the normal range), marked scoliosis, heterometry of lower extremities, impaired left ventricle global function (ejection fraction progressively decreased from 45% to 35% at age10 years) and long QTc. Mutational analysis of ACTA1 gene was negative. At age 10 years, after the discovery of type II diabetes in a cousin 5 years old, she performed oral glucose tolerance test that showed insulin resistance which led us to perform mutational analysis of SEPN1 gene. Our patient suddenly died when she was 11 years old. The association between CFTD and NC in our patient suggest a common pathogenesis, so we investigated for mutations of ACTA1 gene, which have been associated with either conditions. Furthermore, the discover of insulin resistance in the patient and her family made SEPN1 the main candidate gene taking into account the dependance of skeletal and cardiac muscles development from insulin metabolism. INGLESE