Congenital muscular dystrophy (CMD) type 1C belongs to a heterogeneous family of inherited disorders involving muscle weakness at birth. It is a severe form of CMD and is characterized by a highly elevated level of serum creatine kinase (CK), early onset hypotonia, calf pseudohypertrophy, delayed or absent motor development and variable cardiomyopathy generally with normal IQ and brain imaging. However, cases have been identified together with mental retardation and cerebellar cysts.
Louhichi et al. (2004) described an Algerian patient with MDC1C born to consanguineous parents. The patient also had mental retardation, white matter changes on MRI, and cerebellar cysts.
[See also: Tunisia > Louhichi et al., 2004].
Triki et al. (2003) examined three Tunisian patients, all from three unrelated consanguineous families, with hypotonia at birth, mental retardation, contractures and severe psychomotor retardation. All three patients could not speak or walk. Two presented with calf hypertrophy. Cranial magnetic resonance imaging showed cerebellar cysts and hypoplasia of the vermis and muscle biopsy showed dystrophic changes. Serum CK levels were very high and abnormalities of the white matter was present in two of the patients. Immunohistochemical analysis indicated partial merosin deficiency and very low alpha-dytroglycan levels in the only two samples taken. Association to known responsible loci 6q22, 9q31, 1p32 and 1q42 has been ruled out. Later on, Louhichi et al. (2004) added the same three patients to three young girls with severe CMD, also from unrelated consanguineous Tunisian families, between the ages of 5 and 12 with the age of onset at 4 months and 2 months of age. The patients presented with the same symptoms. One presented with calf hypertrophy and one with tongue hypertrophy. The oldest child in the six individuals was the most severely affected with severe facial weakness, progressive weakness and macroglossia. She underwent surgery for scoliosis and had severe restrictive respiratory insufficiency. She had an older brother with CMD associated with encephalopathy, who died from pneumopathy at the age of three. She had a verbal IQ of 50 and cerebral atrophy. Louhichi et al. (2004) were able to determine a new mutation, 1364C-A that leads to the replacement of Alanine to a negatively charged aspartic acid. All patients were homozygous for this mutation and for a rare allele of 120bp with 26 CA repeats suggesting a founder mutation. This and another mutation in the FKRP gene found in an Algerian boy with similar symptoms strongly indicate CNS involvement in this disease phenotype.