What are the signs and symptoms of Ullrich congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Collagen VI–deficient congenital muscular dystrophy is the second most common variant of congenital muscular dystrophy worldwide and was originally described by Ullrich in 1930. Mutations in collagen VI genes (COL6) cause different phenotypes, including Ullrich congenital muscular dystrophy, Bethlem myopathy, and autosomal recessive myosclerosis myopathy. Ullrich congenital muscular dystrophy is usually an autosomal recessive disorder, but the disease has occasionally been reported to be caused by heterozygous mutations in the COL6A1 and COL6A2 genes.

Typical features include presentation in the neonatal period with hypotonia, kyphosis of the spine, proximal joint contractures, torticollis, and hip dislocation. [9]

Combined with the above is distal joint hyperlaxity with a protruding calcaneus. Patients with severe disease may lack hyperlaxity.

Kyphosis and proximal contractures may improve with therapy, but contractures recur and eventually involve previously lax distal joints.

Weakness involves distal more than proximal muscles. Many patients never walk, but some walk for a short time. Progressive disability, usually due to contractures, leads to loss of ambulation after 3-10 years.

Respiratory insufficiency invariably develops in the first or second decade.

Facial dysmorphism is common and includes micrognathia, a round face with drooping of the lower lids, and prominent ears.

Skin changes can include follicular hyperkeratosis, keratosis pilaris, and keloids.

Intelligence and brain MRIs are normal.

Cardiac function is normal.

Bethlem myopathy: Ullrich congenital muscular dystrophy is allelic and shares several features with a more mild myopathy termed Bethlem myopathy. Ullrich congenital muscular dystrophy is typically due to an autosomal recessive mutation in the gene for collagen type VI, whereas Bethlem myopathy is due to autosomal dominant mutations in the same gene. Typical features of Bethlem myopathy include the following:

Onset usually occurs in the first or second decade, but may be as late as the sixth decade.

Flexion contractures of the fingers, wrists, elbows, and ankles are noted. Proximal contractures include at the knees, hips and shoulders. Contractures may improve in childhood.

Joint laxity occurs and may precede the contractures. Lax joints may become contracted.

Patients have hypotonia and proximal muscle weakness and wasting, including respiratory muscles. In rare cases, patients have no weakness.

Weakness is slowly progressive. Patients usually having a normal life expectancy. Mild improvement may occur around puberty. However, adult progression may result in need for a wheelchair after 40-50 years.

Skin changes are similar to Ullrich congenital muscular dystrophy.

In intermediate cases, features of both diseases are noted with childhood-onset weakness, Ullrichlike distal laxity, and Bethlemlike contractures of finger flexors.

In severe cases, congenital contractures, torticollis, hip dislocation, delayed motor milestones, and late loss of ambulation are similar to findings in Ullrich congenital muscular dystrophy.

An LGMD phenotype with proximal weakness and no significant contractures has been described. [10]

Cases described as myosclerosis (contractures without weakness and a woody feeling upon palpation of muscles) have also been described. [11]

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