The clinical phenotype in ASC-1 related myopathy range from very severe congenital forms, lethal in the neonatal period due to severe respiratory involvement, to mild ambulatory adult patients. Overall, the phenotype is characterized by early onset axial and proximal weakness, progressive scoliosis sometimes associated with rigid spine, dysmorphic features, cutaneous involvement and respiratory failure of variable severity. The skin phenotype includes skin hyperlaxity, xerosis and follicular hyperkeratosis. Late-onset dilated cardiomyopathy is also part of the clinical phenotype. The histological presentation include a combination of mild endomysial fibrosis, internalized nuclei, fiber size variation and congenital myopathy lesions such as minicores, rods or cap lesions.
TRIP4 mutations have also been reported in three families with a very severe phenotype marked by arthrogryposis multiplex congenital, severe respiratory involvement and prenatal bone fractures, reported as a form of spinal muscular atrophy. In summary, TRIP4 mutations should be considered in any patient with histopathological features of a congenital myopathy and non-progressive muscular weakness without marked limb contractures, even in ambulant patients without clear neonatal signs, particularly if this phenotype includes respiratory insufficiency, cardiomyopathy or skin abnormalities.
TRIP4