Format

Send to

Choose Destination
See comment in PubMed Commons below

LAMA2-Related Muscular Dystrophy.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
2012 Jun 7.

Excerpt

CLINICAL CHARACTERISTICS:

The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.

DIAGNOSIS/TESTING:

Diagnosis of LAMA2 MD is based on: clinical findings; elevated serum CK concentration; specific abnormal white matter signal on T2-weighted MRI by age one year; complete or partial laminin α2 deficiency on immunohistochemical (IHC) staining of muscle and/or skin; and biallelic mutation of LAMA2, the gene encoding the laminin subunit alpha-2.

MANAGEMENT:

Treatment of manifestations: For infants and children with early-onset LAMA2 MD, multidisciplinary care may include: supplemental feeding and gastrostomy; cough assistance, followed by noninvasive ventilation support (intermittent positive pressure breathing [IPPB] or bilevel ventilation) for respiratory insufficiency; physical therapy and casts, splints, or orthotics for joint contractures; trunk orthotics or braces and spinal fusion as needed for scoliosis. Seizures are treated in a routine manner. Those with late-onset laminin α2 deficiency benefit from regular physical therapy to stretch the joints and spine and may need care for progressive respiratory insufficiency and joint and/or spinal deformities. Surveillance: Early-onset LAMA2 MD: During the first five years biannual follow up by: a dietician/gastroenterologist to assess nutritional intake and swallowing; a pulmonologist to assess respiratory function; a physical therapist to assess strength and joint range of motion; and an orthopedist to assess the spine. After age five years at least annual follow up is recommended if the disease course is stable. In the absence of cardiac symptoms, evaluation by a cardiologist including electrocardiogram and echocardiogram at age five years, ten years, and then every two years is recommended. Late-onset LAMA2 MD: Follow up with a pulmonologist, cardiologist, and physical therapist. Agents/circumstances to avoid: (1) Succinylcholine during induction of anesthesia because of risk of hyperkalemia and cardiac conduction abnormalities; (2) statin, cholesterol-lowering medication because of risk of muscle damage.

GENETIC COUNSELING:

LAMA2-related muscular dystrophy is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

Copyright © 1993-2016, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Support Center