What are the signs and symptoms of FKRP deficiency-associated congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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A wide spectrum of disease phenotypes have been described, from in utero or lethal Walker-Warburg syndrome or muscle-eye-brain disease to intermediate forms; CMD with cerebellar involvement and CMD with mental retardation and microcephaly to a mild limb-girdle muscular dystrophy phenotype.

The severe end of the spectrum includes muscular dystrophy and structural brain abnormalities similar to Walker-Warburg syndrome or muscle-eye-brain disease. Severe cases can manifest with congenital muscular dystrophy, pontocerebellar hypoplasia, cerebellar cysts, agyria, thickening of the frontal cortex, myopia, and retinal detachment causing blindness. Congenital muscular dystrophy with mild mental retardation and cerebellar cysts has been described.

An intermediate form is similar to congenital muscular dystrophy due to laminin-α2 mutations.

  • Presentation is at birth with hypotonia and weakness with delayed motor milestones

  • Some patients can sit or take a few steps in the first decade, but progressive weakness leads to respiratory insufficiency and death or ventilatory dependence in the first or second decade.

  • Hypertrophy of the legs and tongue is noted.

  • Atrophy of proximal muscles and, late in the disease, distal muscles, is common.

  • Facial weakness is usually present.

  • Mild dilated cardiomyopathy can occur.

  • Intelligence and brain MRIs are normal.

The mild form manifests with a limb-girdle phenotype and is allelic with limb-girdle muscular dystrophy type 2I. Presentation varies from the first year to the teens to mid adulthood.

  • With early-onset disease, loss of ambulation occurs in the teens, with subsequent scoliosis and ankle contractures similar to those of Duchenne muscular dystrophy. Muscle and tongue hypertrophy is common. Facial weakness is often present. Respiratory failure in the second decade often leads to death or the need for ventilatory assistance.

  • With onset in the teens or adulthood, ambulation can be preserved until the sixth or seventh decade, but respiratory failure may develop before the sixth or seventh decade.

  • Dilated cardiomyopathy develops in 50% of patients with early- or late-onset weakness.

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