Diagnosis is made by means of:

  1. clinical examination;
  2. CPK dosage;
  3. magnetic resonance imaging or muscle CT scan;
  4. muscle biopsy and skin fibroblast culture (see below);
  5. genetic investigation (see below)

Diagnosis depends on observation of the clinical signs described in the individual disease reports. The creatine kinase (CK) concentration may be fairly high, a muscle biopsy with immunolabelling of Collagen type VI or skin biopsy for analysis of dermal fibroblast cultures to assess the amount of Collagen VI present may be necessary. It is confirmed by genetic analysis, with a search for mutations in the genes involved, although in some cases, in the presence of the classic clinical features, no mutations have been detected in the three genes indicated.

For the differential diagnosis several other syndromes that may be present in a very similar form should be considered. In less severe cases, comparison with Bethlem myopathy is necessary or, in the event of a marked presence of joint hyperlaxity, differential diagnosis with Ehlers-Danlos syndrome or Marfan syndrome may be useful. Comparison with other congenital muscular dystrophy (Congenital Muscular Dystrophy, CMD) subtypes, such as the muscular-eye-brain disease, Walker-Warburg syndrome, merosin-deficient muscular dystrophy (MDC1A) and Fukuyama CMD, could also be useful. However, the latter should be clearly distinguishable from Ullrich, due to the presence of cognitive impairment, which is considered one of the main symptoms.

Muscle biopsy and skin fibroblast culture

– Reduced or absent Col6 in muscle, skin fibroblasts and also in macrophages derived from peripheral blood monocytes in Ullrich DMC.
– Reduced Col6 in muscle and skin fibroblasts cultured in the recessive forms of Bethlem myopathy and myosclerosis. Col6 is not always altered in the dominant forms of Bethlem myopathy.

Genetic testing

– essential to confirm the diagnosis;
– mutations in the COL6A1, COL6A2, COL6A3 genes can be either heterozygous (affecting only one copy of the gene, if transmitted in a dominant manner or arising de novo) or compound homozygous/heterozygous (affecting both copies of the gene and transmitted in a recessive manner).