Clinical Guidance

Prognostication of clinical severity depends on several variables including age at onset of first manifestations, LAMA2 pathogenic variant type, and, if known, the effect of the variant on protein function . See for the phenotypes associated with several commonly reported pathogenic variants. Complete absence of laminin 2 and the phenotype of congenital muscular dystrophy type 1A (MDC1A) in general are caused by loss-of-function LAMA2 variants ; however, exceptions occur, including an individual homozygous for a pathogenic nonsense LAMA2 variant who achieved ambulation . Intrafamilial variation has also been observed . Partial deficiency of laminin 2. The phenotypes associated with partial deficiency of laminin 2 tend to be less severe, with slower disease progression .

Source: GeneReviews — "LAMA2 Muscular Dystrophy"

Diagnostic Criteria

The phenotypic spectrum of LAMA2 muscular dystrophy (LAMA2-MD) ranges from congenital muscular dystrophy type 1A (MDC1A) to LAMA2-MD with onset ranging from early childhood to adulthood (referred to as late-onset LAMA2-MD). No consensus clinical diagnostic criteria for LAMA2-MD have been published.

Suggestive Findings

LAMA2-muscular dystrophy should be suspected in individuals with the following by age of onset; regardless of age; and .

Clinical Findings by Age of Onset

Congenital muscular dystrophy type 1A (MDC1A)

Source: GeneReviews — "LAMA2 Muscular Dystrophy"

Differential Diagnosis

Congenital muscular dystrophy type 1A (MDC1A) must be distinguished from other disorders that may present with profound hypotonia (with frog leg posture of the legs), chest deformity, and breathing and feeding problems. The disorders included in the differential diagnosis are other congenital muscular dystrophies, congenital myopathies, congenital myasthenic syndromes, and spinal muscular atrophy. Of note, these disorders are not typically associated with: (1) laminin-2 deficiency detected by immunohistochemical staining of muscle or skin biopsy, or (2) white matter changes on brain MRI. Additional distinguishing features include: • Progressive improvement of tone and strength (in some affected individuals), CK levels near normal range values, diagnostic structural abnormalities on muscle biopsy (by light and electron microscopy), and an absence of joint contractures (even when the disease is severe) in the congenital myopathies; • Multisystemic presentation (e.g., liver and cardiac involvement besides muscle weakness) in congenital metabolic myopathies. Table 2a. Selected Genes of Interest in the Differential Diagnosis of MDC1A

Management Guidelines

Published consensus clinical practice guidelines for congenital muscular dystrophies list recommendations for the following six clinical care areas: neurology, pulmonary, gastrointestinal/nutritional/oral care, orthopedics and rehabilitation, cardiology, and palliative care (full text). Evaluations Following Initial Diagnosis To establish the extent of disease and needs of a child diagnosed with LAMA2 muscular dystrophy (LAMA2-MD), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with LAMA2 Muscular Dystrophy

Source: GeneReviews — "LAMA2 Muscular Dystrophy"

Clinical Guidance

Avoid the following:

• Succinylcholine in induction of anesthesia because of risk of hyperkalemia and cardiac conduction abnormalities

• Statins, cholesterol-lowering medications, because of the risk of muscle damage

Source: GeneReviews — "LAMA2 Muscular Dystrophy"

Therapies Under Investigation

New treatment strategies are being investigated for LAMA2-MD . Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "LAMA2 Muscular Dystrophy"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with LAMA2 Muscular Dystrophy

Source: GeneReviews — "LAMA2 Muscular Dystrophy"