Congenital muscular dystrophy type 1A

General Information (adopted from Orphanet):

Synonyms, Signs: MDC1A
CMD1A
Muscular dystrophy, congenital Merosin-deficient muscular dystrophy, congenital, due to partial LAMA2 deficiency, included
Merosin-negative congenital muscular dystrophy
Congenital muscular dystrophy due to laminin alpha2 deficiency
Number of Symptoms 35
OrphanetNr: 258
OMIM Id: 607855
ICD-10: G71.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 0.3
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Congenital muscular dystrophy
 -Rare genetic disease
 -Rare neurologic disease
Qualitative or quantitative defects of merosin
 -Rare genetic disease

Comment:

Congenital muscular dystrophy type 1A (MDC1A) is an autosomal recessive disorder characterized by hypotonia, elevated serum creatine kinase level, delayed motor milestones, white matter changes observed by brain magnetic resonance imaging, and normal intelligence. A mutation in the laminin alpha2 (LAMA2) gene, located at 6q22-23, is a genetic cause of MDC1A. Patients have merosin (laminin alpha2)-deficient skeletal muscles (PMID:24778697). In Europe, MDC1A accounts for ~40% of CMD cases (PMID:24223650).

Symptom Information: Sort by abundance 

1
(HPO:0001270) Motor delay 24778697 IBIS 322 / 7739
2
(HPO:0001265) Hyporeflexia 24778697 IBIS 208 / 7739
3
(HPO:0001315) Reduced tendon reflexes 24778697 IBIS 160 / 7739
4
(HPO:0001263) Global developmental delay 24223650 IBIS 853 / 7739
5
(HPO:0001284) Areflexia 24223650 IBIS 198 / 7739
6
(HPO:0003487) Babinski sign 24223650 IBIS 179 / 7739
7
(HPO:0001249) Intellectual disability 24223650 IBIS 1089 / 7739
8
(HPO:0001250) Seizures Occasional [IBIS] 24223650 IBIS 1245 / 7739
9
(HPO:0001371) Flexion contracture 24223650 IBIS 220 / 7739
10
(HPO:0011968) Feeding difficulties Frequent [IBIS] 24223650 IBIS 240 / 7739
11
(HPO:0008872) Feeding difficulties in infancy 24223650 IBIS 153 / 7739
12
(HPO:0003236) Elevated serum creatine phosphokinase Very frequent [IBIS] 24778697 IBIS 214 / 7739
13
(HPO:0002093) Respiratory insufficiency Frequent [IBIS] 24223650 IBIS 410 / 7739
14
(HPO:0002747) Respiratory insufficiency due to muscle weakness 17163796 IBIS 48 / 7739
15
(HPO:0006532) Recurrent pneumonia 17163796 IBIS 48 / 7739
16
(HPO:0001252) Muscular hypotonia Very frequent [IBIS] 24778697 IBIS 990 / 7739
17
(HPO:0003560) Muscular dystrophy 24778697 IBIS 88 / 7739
18
(HPO:0003741) Congenital muscular dystrophy 24778697 IBIS 22 / 7739
19
(HPO:0001324) Muscle weakness 24223650 IBIS 859 / 7739
20
(HPO:0008947) Infantile muscular hypotonia 24223650 IBIS 482 / 7739
21
(HPO:0007103) Hypointensity of cerebral white matter on MRI 24223650 IBIS 3 / 7739
22
(OMIM) Endomysial fibrosis 24778697 IBIS 4 / 7739
23
(OMIM) Absence of merosin in muscle Very frequent [IBIS] 24778697 IBIS 1 / 7739
24
(OMIM) Negative Babinski 24223650 IBIS 2 / 7739
25
(HPO:0001321) Cerebellar hypoplasia Occasional [IBIS] 24223650 IBIS 114 / 7739
26
(OMIM) Hypotonia, infantile, severe 24223650 IBIS 2 / 7739
27
(HPO:0012447) Abnormal myelination 17163796 IBIS 7 / 7739
28
(HPO:0002536) Abnormal cortical gyration 10220863 IBIS 72 / 7739
29
(HPO:0002539) Cortical dysplasia Occasional [IBIS] 24223650 IBIS 19 / 7739
30
(OMIM) Ventricular enlargement Occasional [IBIS] 24223650 IBIS 4 / 7739
31
(HPO:0012110) Hypoplasia of the pons Occasional [IBIS] 24223650 IBIS 16 / 7739
32
(OMIM) Normal intelligence in most cases Very frequent [IBIS] 24223650 IBIS 2 / 7739
33
(HPO:0002126) Polymicrogyria Occasional [IBIS] 24223650 IBIS 64 / 7739
34
(OMIM) Increased endomysial connective tissue around muscle fibers 17163796 IBIS 1 / 7739
35
(OMIM) Absence of laminin alpha-2 chain in muscle 24778697 IBIS 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM - Prenatal Diagnosis

Naom et al. (1997) concluded that immunocytochemical analysis of the laminin alpha-2 chain in the trophoblast can detect abnormalities in affected fetuses and give normal results in unaffected and carrier fetuses. Nonetheless, they ...

Clinical Description OMIM Tome et al. (1994) observed a specific absence of merosin, the laminin isoform in skeletal muscle, and a marked increase in endomysial connective tissue in 13 patients with congenital muscular dystrophy. Tome et al. (1994) investigated laminin because ...
Molecular genetics OMIM In affected members of 2 families with congenital merosin-deficient muscular dystrophy, Helbling-Leclerc et al. (1995) identified 2 different homozygous mutations (156225.0001-156225.0002) in the LAMA2 gene. They suggested that 'the extracellular location of laminin-2 may allow new therapeutic strategies ...
Diagnosis GeneReviews 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). ...
Clinical Description GeneReviews 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). ...
Genotype-Phenotype Correlations GeneReviews Prognostication of clinical severity depends on several variables including: age at first symptom onset, presence/absence of the protein laminin α2 on IHC analysis, mutation type, and, if known, mutation effect on protein function. ...
Differential Diagnosis GeneReviews 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....
Management GeneReviews 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:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....