Muscular Dystrophy, Congenital, Lmna-Related
A number sign (#) is used with this entry because this form of congenital muscular dystrophy (MDC) is caused by heterozygous mutation in the gene encoding lamin A/C (LMNA; 150330) on chromosome 1q22.
See also Emery-Dreifuss muscular dystrophy-2 (EDMD2; 181350), an allelic disorder with overlapping features.
Clinical FeaturesMercuri et al. (2004) reported a patient with LMNA-related congenital muscular dystrophy. The infant lost the ability to roll over at age 5 months, and later showed difficulties in lifting her arms and head. Other features included feeding difficulties, requiring a nasogastric tube, marked axial and limb weakness, talipes foot deformities, and increased serum creatine kinase. She also had a narrow chest and a predominantly diaphragmatic pattern of breathing.
D'Amico et al. (2005) reported an 18-month-old boy with so-called 'dropped head syndrome,' characterized by prominent neck extension weakness. His primary motor milestones were within the normal range, but he had difficulty holding up his head and problems walking at age 12 months. Neurological examination at 15 months confirmed significant neck extensor weakness with mild axial and limb girdle weakness. However, the boy could walk alone, walk up stairs, and rise from a chair, and there was no significant decrease in distal muscle strength. Cardiac examination was normal. Genetic analysis identified a de novo heterozygous 3-bp deletion in the LMNA gene (150330.0050).
Quijano-Roy et al. (2008) described a form of congenital muscular dystrophy with onset in the first year of life in 15 unrelated children. Three patients had severe early-onset disease, with decreased fetal movements in utero, no motor development, severe hypotonia, diffuse limb and axial muscle weakness and atrophy, and talipes foot deformities. There were contractures in the distal limb joints, stiff and hyperextensible spine, and neck weakness. All 3 infants required mechanical ventilation at some point, and 2 of the patients had evidence of cardiac arrhythmia. The remaining 12 children initially acquired head and trunk control and independent ambulation, but most lost head control due to neck extensor weakness, a phenotype consistent with 'dropped head syndrome.' Despite variable severity, there was a consistent clinical pattern overall among the 15 patients. They typically presented with selective axial weakness and wasting of the cervicoaxial muscles. Limb involvement was predominantly proximal in upper extremities and distal in lower extremities. Talipes feet and a rigid spine with thoracic lordosis developed early. Proximal contractures appeared later, most often in lower limbs, sparing the elbows. Ten children required ventilatory support. Cardiac arrhythmias were observed in 4 of the oldest patients, but were symptomatic only in 1. Creatine kinase levels were mild to moderately increased. Muscle biopsies showed dystrophic changes in 9 children and nonspecific myopathic changes in the remaining. Quijano-Roy et al. (2008) concluded that the LMNA mutations identified appeared to correlate with a relatively severe phenotype, broadening the spectrum of laminopathies. The authors suggested that this group of patients may define a new disease entity, which they designated LMNA-related congenital muscular dystrophy.
Early-Onset Myopathy with Progeroid Features
Kirschner et al. (2005) described a young girl with a phenotype combining early-onset myopathy with progeroid features who was found to have a de novo heterozygous mutation in the LMNA gene (S143F; 150330.0034). The child presented during the first year of life with myopathy with marked axial weakness; progeroid features, including growth failure, sclerodermatous skin changes, and osteolytic lesions, developed later. Routine examination at the age of 8 years revealed a mediolateral myocardial infarction. Although LMNA mutations are known to cause Hutchinson-Gilford progeria (HGPS; 176670) and muscular dystrophy, this was the first report of a patient combining features of these 2 phenotypes resulting from a single mutation in LMNA.
Molecular GeneticsIn a patient with LMNA-related congenital muscular dystrophy, Mercuri et al. (2004) identified a de novo heterozygous mutation in the LMNA gene (E3358K; 150330.0049). Four additional unrelated patients with less severe muscular dystrophy (EDMD2; 181350) carried the same mutation.
In 15 children with congenital muscular dystrophy, Quijano-Roy et al. (2008) identified 11 different de novo heterozygous mutations in the LMNA gene (see, e.g., 150330.0047-150330.0049).