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LAMA2-Related Muscular Dystrophy

Synonyms: Early-Onset Laminin Alpha 2 Deficiency, Laminin Alpha 2-Deficient Congenital Muscular Dystrophy, Late-Onset Laminin Alpha 2 Deficiency, MDC1A, Merosin-Deficient Congenital Muscular Dystrophy Type 1A

, MD, PhD, , MD, PhD, and , MD.

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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 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.


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.


  • 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.


Clinical Diagnosis

LAMA2-related muscular dystrophy (LAMA2 MD) manifests in infancy as congenital muscular dystrophy (CMD) (referred to as early-onset LAMA2 MD in this GeneReview) or as childhood onset limb-girdle type muscular dystrophy (referred to as late-onset LAMA2 MD in this GeneReview).

Individuals with early-onset LAMA2 MD are often categorized by:

  • Immunohistochemical (IHC) staining on muscle or skin biopsy as having complete or partial deficiency of laminin α2, the protein encoded by LAMA2;
  • The inability to ambulate (a manifestation of complete laminin α2 deficiency) or ability to ambulate (a manifestation of partial laminin α2 deficiency).


Serum CK concentration is typically elevated for both complete and partial laminin α2 deficiency.

  • In the first years of life, serum CK concentration may be more than fourfold normal values [Hayashi et al 2001, Oliveira et al 2008].
  • In one study, maximum serum CK concentrations ranged from 593 IU/L to 838 IU/L in partial laminin α2 deficiency and 840 IU/L to 6987 IU/L in complete laminin α2 deficiency [Oliveira et al 2008]; normal range is between 200 and 400 depending on the laboratory.
  • Children with complete laminin α2 deficiency who do not achieve walking usually have a serum CK concentration of more than 1000 IU in the first two years of life, with a subsequent decrease in levels.

Immunohistochemistry (IHC) of muscle or skin biopsy. Expression of laminin α2 is evaluated by commercially available antibodies whose epitopes have been mapped; the importance of using antibodies directed against different fragments of the laminin α2 chain has been demonstrated [He et al 2001]. Useful antibodies include those directed against (1) the 80-kd fragment of the carboxy-terminal LG region, (2) the 300-kd amino-terminus fragment, and (3) the entire laminin α2 chain (see Molecular Genetics, Normal gene product).

In 51 individuals with confirmed laminin α2 deficiency, 33 had complete laminin α2 deficiency and 13 had partial deficiency on IHC [Geranmayeh et al 2010].

Note: (1) A consequence of complete deficiency of laminin α2 , encoded by LAMA2, is complete merosin deficiency because laminin α2 is one of three peptide chains that comprise merosin. Merosin (also known as laminin-211) is a heterotrimer comprising the laminin chains α2, β1, and γ1, each encoded by a different gene (see Molecular Genetics). Because merosin deficiency can be primary in LAMA2-related muscular dystrophy or secondary in the dystroglycanopathies (also known as α-dystroglycan-related dystrophy), the term “merosin deficiency” is no longer used because it is not sufficiently specific (see Hara et al [2011]). Of note, early reports of laminin α2 or merosin deficiency generated confusion because they did not distinguish between a direct result of inactivation of LAMA2 and an indirect effect of a dystroglycanopathy. (2) In order to appreciate the reduced laminin α2 chain expression seen in partial laminin α2 deficiency, it may be necessary to use the antibody to the 300-kd fragment. (3) In order to differentiate partial deficiency of laminin α2 caused by mutation of LAMA2 from an indirect result of a dystroglycanopathy, additional IHC staining with IgM antibodies against glycosylated epitopes of α-dystroglycan (IIH6 or VIA41) must be used [Naom et al 1998, He et al 2001]. (4) In laminin α2 deficiency, staining for laminin α4 and α5 (which are upregulated) is increased [Sewry et al 1997, He et al 2001].

Hematoxylin and eosin staining of muscle. Characteristic findings are a dystrophic process early in infancy, including active degeneration, atrophic fibers, increased extracelluar matrix connective tissue, and areas of increased inflammation. Regenerating fibers, while present, are less than anticipated for the degree of degeneration [Hayashi et al 2001].

Brain MRI

  • Abnormal white matter signal on T2-weighted brain MRI is observed in cerebral areas that are myelinated in the developing brain (i.e., subcortical and periventricular areas) with sparing of those areas that are myelinated later in life (i.e., corpus callosum and internal capsule) [Alkan et al 2007]. These abnormalities (likely secondary to leaky basal laminar connections and increased water content) do not represent areas of demyelination and are detected in some children as early as age six months [Alkan et al 2007] and consistently by age one year in those with the early onset form [Leite et al 2005]. The brain MRI findings are seen in both complete and partial laminin α2 deficiency [Geranmayeh et al 2010].
  • Structural brain abnormalities, observed in 5% of affected individuals, may include occipital pachygyria or agyria and pontocerebellar atrophy with accompanying variable cognitive impairment [Mercuri et al 2001, Aslan et al 2005].

Molecular Genetic Testing

Gene. LAMA2 (encoding the laminin subunit α2 protein) is the only gene in which mutation is known to cause LAMA2-related muscular dystrophy.

Table 1.

Molecular Genetic Testing Used in LAMA2-Related Muscular Dystrophy

Gene 1MethodVariants Detected 2Variant Detection Frequency by Method 3
LAMA2Sequence analysis 4Sequence variants 560%-80% 6
Deletion/duplication analysis 7(Multi)exon deletions 520%-40%

See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a variant that is present in the indicated gene


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Commonly reported pathogenic variants (exact prevalence in LAMA2-related muscular dystrophy population unknown) are discussed in Molecular Genetics and Table 2 and include c.2901C>A, c.1854_1861dup, c.2048-2049del, c.7750-1713_78899-2153del4987 (deletion of exon 56), and c.7881T>G.


Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

Testing Strategy

To confirm/establish the diagnosis in a proband

  • Clinical examination demonstrating motor delay and weakness or profound hypotonia in an infant without findings that suggest the diagnosis of spinal muscular atrophy (SMA) (i.e., tongue fasciculation and areflexia)
  • Elevated serum CK concentration
  • Brain MRI demonstrating bilateral white matter high-intensity signal on T2-weighted and FLAIR MRI in periventricular areas and subcortical cerebral hemispheres as early as age six months and consistently at age one year
  • Muscle biopsy with consistent dystrophic appearance, including degeneration, fiber atrophy, and increased extracellular matrix connective tissue
  • Immunohistochemistry (IHC) showing:
    • Complete or partial laminin α2 deficiency (muscle and skin)
    • Increased expression of laminin α4 and α5

Note: In those with typical clinical presentation, serum CK concentration, and brain MRI findings, muscle or skin biopsy is not necessary; LAMA2 molecular genetic testing can be used to confirm the clinical diagnosis.

Carrier testing for at-risk relatives requires prior identification of the pathogenic variants in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variants in the family.

Linkage analysis and evaluation of laminin α2 by immunohistochemistry in chorionic villi may be available in certain specialized laboratories [Vainzof et al 2005].

Clinical Characteristics

Clinical Description

The clinical manifestations of LAMA2-related muscular dystrophy range from severe early-onset congenital muscular dystrophy (CMD) (early-onset LAMA2 MD) to mild later childhood-onset limb-girdle type muscular dystrophy (late-onset LAMA2 MD).

Those with severe disease have neonatal profound hypotonia, poor spontaneous movements, weak cry, and respiratory failure [Jones et al 2001, Gilhuis et al 2002]. Failure to thrive, gastroesophageal reflux, aspiration, and recurrent chest infections necessitating frequent hospitalizations may accompany the early hypotonic presentation. As disease progresses, facial muscle weakness, temporomandibular joint contractures, and macroglossia may further impair feeding and can affect speech.

Late-onset LAMA2 MD is characterized by later-onset proximal weakness and delayed motor milestones. Affected individuals may show muscle hypertrophy and develop a rigid spine syndrome with joint contractures, usually most prominent in the elbows. Progressive respiratory insufficiency and scoliosis can occur [He et al 2001] along with cardiac arrhythmia and cardiomyopathy [Carboni et al 2011].

Affected individuals are often categorized clinically by the ability or inability to achieve independent ambulation. Infants with complete laminin α2 deficiency on IHC staining (see Testing) typically have weakness at birth or in the first six months of life and do not achieve independent ambulation, whereas those with partial laminin α2 deficiency are more likely to have a later-onset, milder clinical course and achieve independent ambulation. (See Genotype-Phenotype Correlations for more details.)

Early-Onset LAMA2-Related Muscular Dystrophy (CMD Phenotype)

Respiratory involvement in LAMA2 MD is caused by a progressively restrictive chest wall that first involves weakness of the intercostal and accessory muscles. Early in childhood the thorax becomes stiff and chest wall compliance decreases, further contributing to alveolar hypoventilation, atelectasis, and mucous plugs with bronchial obstruction. These changes manifest as low lung volumes. Poor secretion clearance resulting from weak cough leads to recurrent chest infection. Swallowing difficulties and gastroesophageal reflux may increase the risk of aspiration. Chest infections may cause atelectasis, which along with limited pulmonary reserve, increases risk of acute respiratory failure in the setting of infection.

Spinal deformity may result early in thoracic and lumbar lordosis, which contribute to the progressive restrictive respiratory insufficiency. Thoracic lordosis, with or without concomitant scoliosis, may cause the bronchial wall to be compressed by the anterior vertebral bodies.

In late adolescence, cervical lordosis may progress to severe neck hyperextension with a significant effect on the quality of life, as well as swallowing and feeding difficulties that increase the risk of aspiration.

The need for ventilatory support is most likely to occur during two time periods [Geranmayeh et al 2010]:

  • Between birth and age five years in the most severely affected children mainly due to respiratory muscle weakness, hypotonia, and fatigue. Depending on age, total hours of ventilatory support required, frequency of hospitalizations, and institutional practice patterns, ventilatory support may be noninvasive or mechanical with tracheostomy. Respiratory issues in these infants and young children often stabilize in the first years, likely as a result of improved muscle tone.
  • Between ages ten and 15 years due to progressive restrictive lung disease leading to respiratory insufficiency [Wallgren-Pettersson et al 2004]. Most children in this age group with the early onset form do not have typical signs/symptoms of hypercapnia (i.e., headaches, attention difficulties, and drowsiness) but rather the more subtle findings including recurrent respiratory infections, failure to thrive, poor cough, and fatigue with feeding.

Feeding difficulties, consistent low weight, failure to thrive, and precipitous drop in weight with infections and hospitalizations are common. Philpot et al [1999a] reported weight below the third centile and feeding difficulties including: swallowing abnormalities, difficulty chewing, and prolonged feeding time. In a study of 46 individuals with LAMA2 MD, 17 required enteral feeding, usually within the first year [Geranmayeh et al 2010]. Of note, children with early-onset LAMA2 MD do not attain normal weight (see Management, Treatment of Manifestations).

Joint contractures that are present in the first year of life progress slowly even in children receiving intensive daily physical therapy. Contractures tend to occur early in the shoulders, elbows, hips, and knees and later in the temporomandibular joints, distal joints, and cervical spine. Contractures often result in significant morbidity and interfere with activities of daily living.

Hyperlaxity of the distal phalanges of the fingers is observed in a number of affected children.

Motor developmental milestones are delayed and often arrested. Most affected children do not acquire independent walking.

Geranmayeh et al [2010] reported only 15% of individuals acquired independent ambulation, the majority of whom (72%) had partial laminin α2 deficiency on muscle biopsy. A smaller proportion gained the ability to walk with assistance but subsequently lost the ability.

Individuals with complete laminin α2 deficiency were much less likely to achieve independent ambulation than those with partial deficiency.

Scoliosis, often aggravated by thoracic lordosis, is frequently observed from the first decade of life [Bentley et al 2001]. It is slowly progressive and may contribute to respiratory insufficiency by restriction of the thorax and compression of the airway.

Facial muscle weakness and macroglossia may become significant in toddlers and children, resulting in typical elongated myopathic facies, with an open mouth and tongue protrusion.

Limitation of eye movements (ophthalmoparesis) may be evident as early as age two years. Initially, limitation of eye movement is most evident on upward (vertical) gaze; however, over time, lateral gaze may become impaired. Down gaze seems to be preserved, as are pupil size and pupillary reflex; ptosis is not observed [Philpot et al 1999b].

Central nervous system (CNS). Cognitive abilities are normal in the majority of affected individuals and do not correlate with brain MRI abnormalities [Messina et al 2010]; however, in a small proportion of individuals, intellectual disability and epilepsy were associated with bilateral occipital pachygyria [Jones et al 2001] or dysplastic cortical changes affecting predominantly the occipital and temporal regions [Sunada et al 1995, Pini et al 1996, Philpot et al 1999b, Leite et al 2005, Geranmayeh et al 2010].

Cognitive impairment, reported in fewer than 7% of individuals [Jones et al 2001, Geranmayeh et al 2010], ranged from mild intellectual disability to communication difficulties.

Absence seizures and partial seizures with secondary generalization develop in 8%-20% of affected children usually in late childhood; because lack of seizures is likely under-reported, the higher figure may be more accurate [Jones et al 2001]. Individuals with cortical dysplasia may develop refractory seizures [Vigliano et al 2009, Geranmayeh et al 2010].

A progressive sensorimotor neuropathy with signs of dysmyelinization may be detected in childhood [Di Muzio et al 2003]. These abnormalities are usually mild or clinically not significant. In contrast, needle EMG shows myopathic signs in the majority of individuals, even when performed early in infancy [Quijano-Roy et al 2004].

Cardiac involvement does not seem to be a major complication of LAMA2 MD. Although early ultrasound studies in merosin deficiency (in which molecular genetic studies were incomplete) found decreased ejection fraction and subclinical left ventricular hypokinesis in approximately one third of affected individuals [Spyrou et al 1998, Jones et al 2001], these results have not been confirmed and cardiac failure is rarely reported [Gilhuis et al 2002].

Anecdotal reports have included one report of cardiac arrhythmia requiring ablation or medical treatment and two reports of sudden death with cardiac arrhythmia, one in the context of a viral infection [SJ Quijano-Roy 2010, personal communication] and recently in an adult with partial merosin deficiency [Carboni et al 2011].

With improved respiratory management resulting in longer survival, cardiac manifestations may be recognized more commonly in older individuals.

Secondary pulmonary hypertension may be observed as a complication of respiratory insufficiency [Geranmayeh et al 2010].

Late-Onset LAMA2-Related Muscular Dystrophy (LGMD Phenotype)

Rarely individuals with partial laminin α2 deficiency have onset after infancy manifest as delay in walking or proximal muscle weakness, and are typically classified as having limb-girdle muscular dystrophy. Individuals with this milder phenotype may show muscle pseudohypertrophy and/or rigid spine. In general, additional findings include high serum creatine kinase (CK) concentrations, dystrophic muscle changes, abnormal brain MRI, and abnormal nerve conduction studies.

A recent case report describes two sibs with classic brain MRI white matter abnormalities, seizures, and proximal muscle weakness. In addition, muscle histology show dystrophic features, rimmed vacuoles, and partial decrease in laminin α2 staining; molecular testing confirmed the diagnosis [Rajakulendran et al 2011].

Other Studies in Persons with LAMA2 MD

Visual evoked potentials and somatosensory potentials show increased latency in older children with normal visual function, even in those with white matter involvement of the occipital lobes and abnormal visual evoked potentials [Mercuri et al 1998].

Pathophysiology. LAMA2 MD is not a true leukodystrophy; the physiologic basis of the white matter abnormalities observed on brain MRI is not fully understood. Although white matter changes were initially thought to represent hypomyelination, recent studies using both brain MR spectroscopy and diffusion weighted imaging have identified abnormal water content thought to be related to leaky basement membrane connections rather than hypomyelination [Leite et al 2005, Alkan et al 2007].

In particular, brain MR spectroscopy (MRS) reveals very low N-acetylaspartate, N-acetylaspartylglutamate, creatine, and phosphocreatine, findings that suggest a relative astrocytosis and an increased water signal with possible edema within the white matter [Leite et al 2005]. These findings are hypothesized to result from increased permeability of the blood-brain barrier due to the absence of laminin α2 in the basal lamina of the cells of the cerebral blood vessels.

Laminin α2 is also present in Schwann cells. Thus, deficiency of laminin α2 may partially explain the progressive sensorimotor axonal polyneuropathy seen in many individuals with laminin α2 deficiency [Quijano-Roy et al 2004]; however, the clinical significance of the neuropathy and its contribution to the primary muscle disorder are not currently understood.

In post-mortem studies, the white matter of the brain is pale and spongiform with astrocytosis and demyelinization.

Genotype-Phenotype Correlations

Prognostication of clinical severity depends on several variables including: age at first symptom onset, presence/absence of the protein laminin α2 on IHC analysis, pathogenic variant type, and, if known, effect of the variant on protein function.

Genotype-phenotype correlations in LAMA2-related muscular dystrophy (LAMA2 MD) are emerging through publications of small cohorts. A recently launched effort, CMD GaP (genotype and phenotype), led by the National Center for Biotechnology Information (NCBI) and the National Institute of Neurologic Disease and Stroke (NINDS) (both of the National Institutes of Health), Cure CMD, and a consortium of national and international laboratories (Table A) will contribute.

In a study of 51 individuals with confirmed LAMA2 MD, those with complete deficiency presented earlier (age <7 days) (p=0.0073), were more likely to lack independent ambulation (p=0.0215), and were more likely to require enteral feeding (p=0.0099) and ventilatory support (p=0.0354) than those with partial laminin α2 deficiency [Geranmayeh et al 2010].

Complete absence of laminin α2 and the early-onset severe phenotype in general are caused by pathogenic nonsense variants [Pegoraro et al 1998, Oliveira et al 2008]; however, exceptions occur, including an individual homozygous for a pathogenic nonsense variant who achieved ambulation [Geranmayeh et al 2010].

Partial deficiency can be caused by homozygosity for missense variants and for in-frame deletions and by compound heterozygosity for a null variant and an in-frame deletion or exon-skipping variant [Naom et al 1998, Allamand & Guicheney 2002, Tezak et al 2003, Siala et al 2007]. However, in-frame deletions involving the G-domain that mediates binding to α-dystroglycan and α7β1 integrin result in a severe early-onset phenotype even when IHC analysis reveals partial laminin α2 deficiency on muscle biopsy [Naom et al 1998, Allamand & Guicheney 2002, Tezak et al 2003, Siala et al 2007].

Partial laminin α2 deficiency may also be caused by a pathogenic variant in the conserved cysteine residues on the short arm of the laminin α2 protein [Allamand & Guicheney 2002].

Although the ability to ambulate is generally correlated with the presence of laminin α2 on muscle biopsy, a limited number of children with complete laminin α2 deficiency have achieved ambulation and conversely some children with partial laminin α2 deficiency have had early-onset disease and no ambulation. Geranmayeh et al [2010] found that among 51 persons studied, two of 33 with absence of laminin α2 staining on muscle biopsy achieved independent ambulation, one with a heterozygous frameshift variant and a pathogenic missense variant, and one homozygous for a Kenyan founder variant (c.7881T>G). Of note, three in this cohort with the Kenyan founder variant did not acquire ambulation, demonstrating the lack of consistent genotype-phenotype correlations and variability in clinical presentation.

See Molecular Genetics, Pathogenic variants for the phenotypes associated with several commonly reported pathogenic variants.


LAMA2-related muscular dystrophy is also known as “merosin-deficient congenital muscular dystrophy type 1A (MDC1A [muscular dystrophy, congenital, type 1A])” in the international classification, based on the observation (prior to discovery of LAMA2) that individuals with CMD often showed complete or partial absence of merosin by IHC analysis of muscle biopsy.

A nomenclature system that describes which chains are present in each laminin isoform gives merosin the name laminin-211 because it comprises chains α2, β1, and γ1.

Previously the terms "complete and partial merosin deficiency" based on IHC staining were used before it was known that the defect was laminin α2 deficiency. These old diagnostic terms are not relevant now, given that: (1) the diagnosis of LAMA2-related muscular dystrophy can be made with certainty by detection of biallelic pathogenic variants in LAMA2; and (2) merosin deficiency can be primary, caused by biallelic pathogenic variants in LAMA2, or secondary (indirect), caused by biallelic pathogenic variants in one of the dystrophinopathy genes (See Testing, Immunohistochemistry).


Exact prevalence of early-onset LAMA2 MD is unknown. In general, the prevalence of CMDs has been estimated between 0.7/100,000 (based on a 1996 report from northeast Italy that predates molecular genetic testing [Mostacciuolo et al 1996]) and 2.5/100,000 (in a study in western Sweden [Darin & Tulinius 2000]).

Regional prevalence is variable: early-onset LAMA2 MD accounts for about 30% of the CMD cases in European countries, but only 6% in Japan [Allamand & Guicheney 2002].

Differential Diagnosis

Early-onset LAMA2-related muscular dystrophy is in the differential diagnosis of infantile hypotonia with or without respiratory distress and delayed acquisition of motor milestones. Late-onset LAMA2 MD is in the differential diagnosis of childhood-onset weakness of the limb-girdle type.

Early-onset LAMA2 MD needs to be differentiated from:

Early-onset LAMA2 MD is easily distinguished from the above disorders because they are not typically associated with: (1) high serum CK concentrations, (2) merosin deficiency detected by immunohistochemical (IHC) staining of muscle or skin biopsy, or (3) white matter changes on brain MRI.

Clinical examination can also assist in distinguishing them from LAMA2 MD. Although all may present with profound hypotonia (with frog leg posture of the legs), chest deformity, and breathing and feeding problems, the following findings may be distinguishing:

  • Congenital myopathies may show some fibrosis on muscle biopsy, but are excluded mainly based on the presence of diagnostic structural abnormalities on light and electron microscopy (e.g., nemaline myopathy, central core myopathy, centronuclear/myotubular myopathy, minicore myopathy). These congenital myopathies (as well as the metabolic and myasthenic myopathies) may show progressive improvement of tone and strength; diffuse joint contractures do not occur even in those with severe disease.
  • Distinctive clinical findings may be observed from an early age in some: ophthalmoplegia and facial bulbar weakness in centronuclear/myotubular myopathy; facial and bulbar weakness in nemaline myopathy and congenital myasthenic syndromes (CMS); malignant hyperthermia in central core disease; striking motor variability in CMS and metabolic myopathies.
  • Spinal muscular atrophy (SMA) shows relatively rapid motor impairment and tongue fasciculations. EMG and muscle biopsy findings suggest a denervation-reinnervation profile; nerve conduction studies are normal.

Secondary deficiency of the protein laminin α2 may result from another type of dystroglycanopathy.

Late-onset LAMA2 MD (the limb-girdle muscular dystrophy phenotype) needs to be differentiated from other forms of limb girdle muscular dystrophy. Elbow contractures, high serum CK concentrations, and prominent spinal rigidity may lead to a phenotype overlapping with Emery-Dreifuss myopathy (EDMD); however, in contrast to EDMD, LAMA2 MD lacks major cardiac involvement.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of a child diagnosed with LAMA2-related muscular dystrophy following the initial diagnosis, the following are recommended:

  • Assessment of feeding, nutrition, and bone health: measurement of weight and serum concentrations of vitamin D and calcium
  • Systematic inquiry of parents/caregivers regarding digestive complications, in particular dysphagia, GE-reflux, and constipation. Frequent choking, prolonged feeding, and nocturnal cough may identify swallowing and gastroesophageal disorders. Additional assessment may include endoscopy, manometry, PH-meter studies, and videofluoroscopy.
  • Lung function tests that ideally include spirometry (forced vital capacity, forced expired volume in the first second [FEV-1]) and assessment of cough effectiveness (cough peak flow and maximum inspiratory and expiratory pressures)
    • Evaluate older children with an FVC lower than 60% of the predicted value with polysomnography or, if polysomnography is not routinely performed, overnight oximetry.
    • In those using orthopedic trunk braces or orthoses, assess pulmonary function with and without the brace to determine whether thoracic excursion (and thus ventilator function) is impaired.
  • Evaluation for nocturnal hypoventilation in children with a history of recurrent respiratory infections, failure to thrive, poor cry, and/or feeding fatigue
  • Physical therapy assessment of muscle strength and joint mobility
  • Assessment of the spine by an orthopedist regarding the need for early bracing
  • Evaluation by a child neurologist for seizures or unexplained fainting or loss of consciousness.
  • Developmental assessment
  • Neuropsychological testing if learning or behavioral deficiencies are identified
  • Evaluation by a cardiologist including electrocardiogram and echocardiogram
  • Evaluation of respite care services for caregivers
  • Educational planning to place the child with necessary support in the least restrictive educational environment

Treatment of Manifestations

Early-Onset LAMA2 MD

Nutrition/weight. In the absence of evidence-based target BMI or weight charts, the recommendation is to weigh the child serially and assess the frequency of chest infections and hospitalizations. Weight needs to increase annually by small increments. Since these children are usually non-ambulatory and muscular mass is reduced, normalization of weight to standard weights is not the goal. In contrast, excess weight may contribute to reduced motor function, resulting in increased respiratory dysfunction.

If weight plateaus or decreases, assessment of nutrition and diet, speech and swallowing, and respiratory function by a multidisciplinary team of specialists is recommended:

  • The patient or caregiver may need to be prompted to recall dietary concerns including lengthy meal times, limited food intake, and/or significant constipation [Philpot et al 1999a]. Non-ambulant school-age children (because they require assistance to use the restroom) may consciously restrict liquid intake. Limited hydration, choice of diet, and lack of movement may all contribute to constipation, leading to further restriction of oral intake.
  • The nutritionist can review dietary fiber, total liquid consumption, and the need for laxatives (e.g., Miralax®, macromolecules FORLAX®) to optimize caloric intake during periods of growth.
  • If weight continues to decline, respiratory assessment to evaluate for pulmonary infection is indicated.

Adequate weight gain may be achieved by increasing the caloric content of formulas in infants and by supplementary hypercaloric protein drinks in older children.

  • Infants with persistently poor weight gain and frequent pulmonary infections should be referred to a gastroenterologist:
  • Gastroesophageal reflux is treated as needed.
  • A nasogastric tube or percutaneous gastrostomy may help avoid aspiration pneumonia and improve nutritional status.
  • Failure to thrive may require supplemental feeding and gastrostomy with or without Nissen fundoplication [Philpot et al 1999a].
  • Children with poor intake or vomiting may require enteral feeding or intravenous fluid therapy to avoid hypoglycemia and metabolic decompensation.

Calcium and vitamin D supplementation is recommended to support bone growth and strength and to prevent future osteopenia.

Respiratory function testing. Training five year olds to perform spirometry during regular clinic visits may allow them to become adept at performing pulmonary function tests by age six years. (Note: A training effect may lead to an initial improvement in spirometric values.) For those who cannot use a standard mouth piece due to facial weakness, a buco-nasal mask adapter or scuba mouth piece can be used.

Pulmonary function tests ideally include spirometry (forced vital capacity [FVC], forced expired volume in the first second [FEV-1]) and measures of cough effectiveness (cough peak flow and maximum inspiratory and expiratory pressures). Note: In those using orthopedic trunk braces or orthoses, assess pulmonary function with and without the brace to determine if thoracic excursion is impaired.

An FVC less than 60% of the predicted value has been associated with sleep-disordered breathing; an FVC less than 40% of predicted has been associated with high risk for nocturnal hypoventilation [Mellies et al 2003].

  • Those with an FVC less than 60% of predicted or clinical evidence of disordered sleep (daytime somnolence, morning headaches, hypercarbia) should undergo an overnight sleep study (polysomnogram) to evaluate for night-time hypoventilation, hypercapnia, and obstructive sleep apnea.
  • Those with an FVC less than 60% of predicted and hypercapnia, hypoxemia, and/or significant aspiration of food or refluxed gastric contents should be referred to a pulmonologist.
  • Assessment of hypoventilation, night-time and daytime hypercapnea is indicated in children with signs of sleep-related difficulties (e.g., morning headaches, attention difficulties, hypersomnolence, increased fatigue), weight loss, recurrent pulmonary infections, a weak cry, and/or FVC less than 60% of predicted.
  • Because early respiratory insufficiency may not be detected by diurnal tests, polysomnography (including end-tidal CO2 measurements) can be used to evaluate for nocturnal hypoventilation and other sleep-related breathing difficulties, such as apnea (both obstructive and central) and hypopnea, which are usually more pronounced during REM sleep. (The predominance of findings in REM sleep may be the result of diminished respiratory drive, atonia of the upper airway and intercostal muscles, and weakness of the diaphragm.)

Assistance with coughing. Weak/ineffective cough can lead to progressive atelectasis, infection, and respiratory failure in those with diminished lung capacity.

Daily intermittent positive pressure breathing (IPPB) may improve diminished compliance, peak cough flow, and ability to clear secretions. It has been shown to promote expansion of the thorax, prevent or treat atelectasis, and decrease the risk of lower-respiratory infections [Mellies et al 2005, Wang et al 2010]. Positive pressure breathing can be administered by IPPB or a mechanical in-exsufflator (Cough Assist), or attained through breath-stacking maneuvers using a bag valve mask. Patients with weak cough (low cough peak flow, maximum and inspiratory pressures <60 cm H2O, and FVCs <60% predicted) can benefit from use of positive pressure breathing once or twice a day and then as needed during respiratory infections. Night-time ventilator support once initiated also helps inflate the lungs, allowing for better tidal volume and ventilation, and thus preventing atelectasis.

Because of abdominal muscle weakness and the need for high positive pressures, an abdominal belt can lead to better results, efficacy, and tolerance [Guérin et al 2010].

Noninvasive ventilation support is indicated in the setting of:

  • Daytime hypercapnea and/or nocturnal hypoventilation
  • Evidence on polysomnogram of sleep-disordered breathing (even without hypoventilation)
  • Recurrent chest infections or atelectasis (in the absence of either daytime hypercapnea or nocturnal hypoventilation) in infants and toddlers [SJ Quijano-Roy, personal communication]

Noninvasive ventilator interfaces include nasal pillows, nasal masks, and full face masks, all of which come with head gear. Of note, it is difficult to fit masks to infants; toddlers often fight the masks.

In children, alternating mask interfaces is recommended to prevent the progressive under-bite and midface hypoplasia that result from the bone remodeling associated with long-term use of nasal masks from an early age. Although the nasal mask causes more bite and mid-face problems than does the full face mask, the full face mask should be used with caution because of the risk of suffocation in a child who vomits into the mask and is unable to remove it.

In patients with severe lordosis/scoliosis and chronic cough or recurrent infections, chest CT may be needed to evaluate for chronic atelectasis and airway compression by the vertebral bodies

During adolescence ventilatory support is often only needed during sleep with noninvasive pressure support. Assessment of daytime hypercapnea is needed beginning in late adolescence or if patient experiences increasing fatigue, chest infections, or failure to thrive. If daytime ventilation is required, ventilation via tracheostomy may be indicated.

Joint contractures. Physical therapy including daily stander placement, stretching activities, and pool (swimming) therapy can assist in maintenance of some range of motion.

Splints, orthoses, and night positioning by casts are used to prevent progression of joint deformities.

Non-ambulant children require standing frames for postural support.

Durable medical equipment support including power wheelchair fitting is essential for non-ambulant toddlers.

Scoliosis may need orthopedic and surgical treatment [Bentley et al 2001]. When needed, specific trunk orthotics or braces that do not restrict the thorax either through compression or limitation of thoracic movements are recommended [Wang et al 2010]. Their use may improve upright posture and delay spinal fusion until early puberty, providing that bracing does not interfere with respiration by causing chest compression [Wang et al 2010].

If cervical lordosis progresses in late adolescence, posterior head support (using trunk braces or wheelchair supports) can prevent neck hyperextension.

Cardiomyopathy. Right heart failure due to respiratory insufficiency requires adequate mechanical ventilation. Primary left heart failure or rhythm disturbances require typical age-appropriate treatment.

Seizures are generally well controlled with routine administration of antiepileptic drugs. Refractory seizures in those with cortical dysplasia may require polytherapy.

Developmental delay/cognitive impairment. Early intervention with physical, occupational, and speech therapy along with a multidisciplinary medical team provide the best possible outcome.

Other. Surgery to correct facial function and address cosmetic concerns has been performed [Jones & Waite 2012].

Late-Onset LAMA2 MD

These patients need mainly respiratory and orthopedic care due to the risk of progressive respiratory insufficiency and joint and spinal deformities. Regular physical therapy for stretching limbs, shoulder and pelvic girdle, and spine is mandatory.

Antiepileptic drugs should be used to treat seizures.


Standards of care have been reviewed recently [Wang et al 2010] (full text).

Early-onset LAMA2 MD

  • At least biannual evaluations during the first five years by a nutritionist and gastroenterologist to monitor weight gain and to identify early recurrent aspiration
  • At least annual follow up with a pulmonologist to assess respiratory function. After age four to six years: annual pulmonary function testing including assessment of forced vital capacity (FVC).
  • Annual measurement of FVC to allow trending of FVC
  • Annual evaluation of strength and joint range of motion by a physical therapist
  • At least annual evaluation of the spine by an orthopedist. Note: (1) More frequent evaluations are warranted during periods of rapid growth, loss of function, and/or progression of deformities. (2) Annual lateral spinal x-rays (in addition to the standard anterior-posterior x-rays) can be used to evaluate the anterior posterior intra-thoracic cavity diameter; however, if respiratory function declines rapidly without known cause or without prior spinal surgery, a CT may be needed.
  • Cardiac monitoring:
    • In the absence of symptoms, evaluation by a cardiologist including electrocardiogram and echocardiogram at age five years, ten years, and then every two years
    • In patients with severe respiratory insufficiency on mechanical ventilation, annual echocardiography (required)
    • In patients reporting palpitations, increased fatigue, or loss of consciousness without a clear neurologic origin, cardiac evaluation including Holter monitor and echocardiogram (recommended)
    • Pre-surgical cardiac evaluation including Holter monitor, echocardiogram, and a dopamine test of cardiac function

Note: The brain MRI findings seen in both complete and partial laminin α2 deficiency do not need to be followed with serial scans over time [Geranmayeh et al 2010].

Late-onset LAMA2 MD

  • Respiratory. Monitor for respiratory insufficiency with serial pulmonary function tests.
  • Orthopedic. Monitor with frequent spinal examinations to detect scoliosis and assess bone health.
  • Neurologic. Monitor to detect and treat seizures.

Agents/Circumstances to Avoid

Avoid the following:

  • Succinylcholine in induction of anesthesia because of risk of hyperkalemia and cardiac conduction abnormalities
  • Statin, cholesterol lowering medication, because of the risk of muscle damage

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

LAMA2-related muscular dystrophy leads to a primary deficiency of the protein laminin α2 in the extracellular matrix of muscle, precipitating several downstream effects including: increased inflammation, increased fibrosis, increased apoptosis, and decreased regeneration.

Several therapies have recently been tested in murine models that replicate disease pathogenesis (including the dyw and dy3k [neo cassettes in LAMA2] and dy2j [a spontaneously occurring pathogenic variant]). Current efforts to define standard operating protocols led by TREAT-NMD, a panel of international scientists and Cure CMD, have been posted at

Therapies currently under investigation target apoptosis with drugs such as omigapil [Erb et al 2009] and doxycycline [Girgenrath et al 2009], and genetic manipulation of BAX [Girgenrath et al 2004]. Additional approaches include protein replacement therapy using miniagrin constructs and pro-regenerative approaches using IgF [Kumar et al 2011].

Another approach for the treatment of genetic disorders caused by premature termination codons is the use of drugs to force stop codon read-through [Allamand et al 2008].

Search in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

LAMA2-related muscular dystrophy (LAMA2 MD) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one mutated allele).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • 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.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with LAMA2 MD are obligate heterozygotes (carriers) for a pathogenic LAMA2 variant.

Other family members. Each sib of the proband’s parents is at a 50% risk of being a carrier.

Carrier (Heterozygote) Detection

Carrier testing for at-risk family members is possible if the pathogenic variants in the family have been identified.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are carriers or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Molecular genetic testing. Once the LAMA2 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

Linkage and immunohistochemistry. When two LAMA2 pathogenic variants are not identified in the family, linkage analysis and evaluation of laminin α2 by immunohistochemical (IHC) staining in chorionic villi may be available in certain specialized laboratories [Vainzof et al 2005].


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Association Francaise contre les Myopathies (AFM)
    1 Rue de l'International
    Evry cedex 91002
    Phone: +33 01 69 47 28 28
  • Cure CMD
    19401 South Vermont Avenue
    Suite J100
    Torrance CA 90502
    Phone: 323-250-2399
    Fax: 310-684-2023
  • European Neuromuscular Centre (ENMC)
    Lt Gen van Heutszlaan 6
    3743 JN Baarn
    Phone: 31 35 5480481
    Fax: 31 35 5480499
  • Japan Muscular Dystrophy Association
    3-43-11 Fukushi Zaidan Bldg
    Tokyo 170-0005
    Phone: 81-3-6907-3521
  • Muscular Dystrophy Association - USA (MDA)
    222 South Riverside Plaza
    Suite 1500
    Chicago IL 60606
    Phone: 800-572-1717
  • Muscular Dystrophy UK
    61A Great Suffolk Street
    London SE1 0BU
    United Kingdom
    Phone: 0800 652 6352 (toll-free); 020 7803 4800
  • Congenital Muscle Disease International Registry (CMDIR)
    The CMDIR is a patient self-report registry with the goal to register the global congenital muscle disease population including persons with congenital myopathy, congenital muscular dystrophy, and congenital myasthenic syndrome. The CMDIR registers affected individuals of all ages with symptoms from birth through late onset (limb-girdle). Registrants will receive educational information and connections to others in the CMD community, and will be contacted about potential participation in clinical trials for their CMD subtype.
    19401 South Vermont Avenue
    Suite J100
    Torrance CA 90502
    Phone: 323-250-2399
    Fax: 310-684-2023

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

LAMA2-Related Muscular Dystrophy: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for LAMA2-Related Muscular Dystrophy (View All in OMIM)


Molecular Pathogenesis

The phenotype of LAMA2 MD is caused by deficiency in the basal lamina of muscle fibers of the α2 chain of laminins 2 and 4 (encoded by LAMA2). Hypotheses regarding the pathogenesis of LAMA2 MD resulting in congenital muscular dystrophy include: disruption of cellular signaling; disruption of nerve-muscle interaction leading to denervation atrophy; and mechanical instability. The most likely hypothesis from studies with zebrafish is one of mechanical instability of the sarcolemma resulting in cellular damage and subsequent apoptosis [Hall et al 2007].

Gene structure. LAMA2 spans 260 kb and the longest transcript variant (NM_000426.3) has 65 exons and a very large mRNA of 9.5 kb. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. The majority of pathogenic alleles are missense, nonsense, or splicing variants and small deletions, insertions, or duplications within exons that are readily detected by sequence analysis of the coding and associated flanking intronic regions. To date, 94 distinct pathogenic variants distributed throughout the gene have been reported in the LAMA2 locus-specific database (Table A), the majority of which are small out-of-frame deletions (31.9%) and nonsense variants (29.8%). Others include splice variants (16.0%), missense substitutions (14.9%), and small duplications (7.4%) [Oliveira et al 2008].

Commonly reported pathogenic variants (exact prevalence in early-onset LAMA2 MD population unknown) included in Table 2 are c.2901C>A, c.1854_1861dup, c.2048-2049del, c.7750-1713_78899-2153del4987 (deletion of exon 56), and c.7881T>G.

Commonly reported pathogenic variants (Table 1 and Table 2) include the following:

Table 2.

Selected LAMA2 Pathogenic Variants

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences
(2048_2049del 1)
c.7750-1713_78899-2153del4987 2
(~5 kb deletion)

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​ See Quick Reference for an explanation of nomenclature.


Variant designation that does not conform to current naming conventions


Normal gene product. Laminins are a group of heterotrimeric glycoproteins composed of a heavy α chain and two light chains, β and γ, each of which is encoded by a separate gene. To date, five α chains (designated α1 to α5), four β chains (β1 to β3), and three γ chains (γ1 to γ3) have been identified, which combine to form 15 laminin isoforms, each with tissue and/or developmental stage-specific expression [Suzuki et al 2005]. In skeletal muscle, the predominant isoforms are laminin α2 (also known as merosin), which is composed of α2, α1, and γ1 chains and laminin-4, composed of α2, β2, and γ1 chains. Laminins are secreted into the extracellular matrix where they bind to neurexin, agrin, and collagen IV in the extracellular matrix and to dystroglycan and integrins in the sarcolemmal membrane [Muntoni & Voit 2004]. The biologic functions of laminins are varied and include cell-cell recognition, growth, differentiation, cell shape, and migration [Suzuki et al 2005].

LAMA2 encodes a 400-kd protein that is post-translationally cleaved into 300-kd and 80-kd subunits, which remain associated by disulfide bonds. Laminin α2 is expressed in the striated muscle basement membrane, the cerebral blood vessels including the capillaries that form the blood-brain barrier, the glia limitans, the developing axon tracts, and Schwann cells.

Abnormal gene product. Pathogenic loss-of-function variants in LAMA2 typically lead to early-onset LAMA2 MD.


Published Guidelines / Consensus Statements

  • Wang CH, Bonnemann CG, Rutkowski A, Sejersen T, Bellini J, Battista V, Florence JM, Schara U, Schuler PM, Wahbi K, Aloysius A, Bash RO, Béroud C, Bertini E, Bushby K,Cohn D, Connolly AM, Deconinck N, Desguerre I, Eagle M, Estournet-Mathiaud B, Ferreiro A, Fujak A, Goemans N, Iannaccone ST, Jouinot P, Main M, Melacini P, Mueller-Felber W, Muntoni F, Nelson LL, Rahbek J, Quijano-Roy S, Sewry C, Storhaug K, Simonds A, Tseng B, Vajsar J, Vianello A, Zeller R. Consensus statement on standard of care for congenital muscular dystrophies. Available online. 2010. Accessed 10-23-19.

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Chapter Notes

Author Notes

Susan Sparks, MD, PhD is a board-certified pediatrician with additional board certifications in Clinical Genetics and Clinical Biochemical Genetics. At the Children’s National Medical Center (CNMC) in Washington, DC under the direction of Dr Eric Hoffman at CNMC, Dr Sparks was awarded a Wellstone fellowship to do research in the clinical, molecular, and biochemical characterization of muscular dystrophies caused by a defect in O-linked glycan synthesis, a group known as the dystroglycanopathies. The dystroglycanopathies range clinically from congenital onset of muscular dystrophy with CNS and eye involvement, to a later onset form of limb-girdle muscular dystrophy (LGMD), without any CNS or eye involvement. Dr Sparks is also involved in the clinical characterization and evaluation of congenital muscular dystrophies and limb-girdle muscular dystrophies and has experience in preclinical and clinical trials in Duchenne muscular dystrophy. She is currently a medical director for genetic diseases with Genzyme, a Sanofi company.

Anne Rutkowski is chairman of Cure CMD, a nonprofit advocating for CMD awareness and treatment. Cure CMD is an all-volunteer organization that has led the path to building infrastructure to enable clinical trials, including the CMD International Registry (CMDIR) and CMD Care Guidelines. To get to clinical trials requires genetic confirmation and localization of the global CMD population. For more information, visit and

Revision History

  • 7 June 2012 (me) Review posted live
  • 16 March 2010 (ss) Initial submission
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