congenital merosin-deficient muscular dystrophy 1A

Summary

congenital merosin-deficient muscular dystrophy 1A (MONDO:0011925) is a disease caused by LAMA2 (GenCC Definitive), with 1 cohort gene and 8 clinical trials.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LAMA2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 781
• Phenotypes (HPO): 54
• Clinical trials: 8

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.8	Worldwide	Validated
Point prevalence	1-9 / 100 000	1	Europe	Validated
Point prevalence	1-9 / 1 000 000	0.2	Eastern Mediterranean Asia	Validated
Point prevalence	1-9 / 1 000 000	0.6	United Kingdom	Validated

Signs & symptoms

Clinical features (HPO)

54 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0003560	Muscular dystrophy	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0001612	Weak cry	Very frequent (80-99%)
HP:0001939	Abnormality of metabolism/homeostasis	Very frequent (80-99%)
HP:0002020	Gastroesophageal reflux	Very frequent (80-99%)
HP:0002375	Hypokinesia	Very frequent (80-99%)
HP:0002540	Inability to walk	Very frequent (80-99%)
HP:0002878	Respiratory failure	Very frequent (80-99%)
HP:0009025	Increased connective tissue	Very frequent (80-99%)
HP:0030091	Absent muscle fiber merosin	Very frequent (80-99%)
HP:0030234	Highly elevated creatine kinase	Very frequent (80-99%)
HP:0100295	Muscle fiber atrophy	Very frequent (80-99%)
HP:0100614	Myositis	Very frequent (80-99%)
HP:0000158	Macroglossia	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001371	Flexion contracture	Frequent (30-79%)
HP:0002181	Cerebral edema	Frequent (30-79%)
HP:0002446	Astrocytosis	Frequent (30-79%)
HP:0002783	Recurrent lower respiratory tract infections	Frequent (30-79%)
HP:0002835	Aspiration	Frequent (30-79%)
HP:0003457	EMG abnormality	Frequent (30-79%)
HP:0005216	Impaired mastication	Frequent (30-79%)
HP:0010628	Facial palsy	Frequent (30-79%)
HP:0010754	Abnormality of the temporomandibular joint	Frequent (30-79%)
HP:0012747	Abnormal brainstem MRI signal intensity	Frequent (30-79%)
HP:0000194	Open mouth	Occasional (5-29%)
HP:0000649	Abnormality of visual evoked potentials	Occasional (5-29%)
HP:0001302	Pachygyria	Occasional (5-29%)
HP:0001315	Reduced tendon reflexes	Occasional (5-29%)
HP:0001319	Neonatal hypotonia	Occasional (5-29%)
HP:0001339	Lissencephaly	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002058	Myopathic facies	Occasional (5-29%)
HP:0002121	Generalized non-motor (absence) seizure	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002791	Hypoventilation	Occasional (5-29%)
HP:0003307	Hyperlordosis	Occasional (5-29%)
HP:0004325	Decreased body weight	Occasional (5-29%)
HP:0004878	Intercostal muscle weakness	Occasional (5-29%)
HP:0006879	Pontocerebellar atrophy	Occasional (5-29%)
HP:0007141	Sensorimotor neuropathy	Occasional (5-29%)
HP:0007359	Focal-onset seizure	Occasional (5-29%)
HP:0010808	Protruding tongue	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0012664	Reduced left ventricular ejection fraction	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital merosin-deficient muscular dystrophy 1A
Mondo ID	MONDO:0011925
OMIM	607855
Orphanet	258
DOID	DOID:0110636
NCIT	C118783
SNOMED CT	111503008
UMLS	C1263858
MedGen	224728
GARD	0003843
Is cancer (heuristic)	no

Also known as: CMD1A · congenital merosin-deficient muscular dystrophy type 1A · congenital muscular dystrophy caused by mutation in LAMA2 · congenital muscular dystrophy due to laminin alpha2 deficiency · LAMA2 congenital muscular dystrophy · LAMA2-related muscular dystrophy · laminin alpha-2 deficiency · MDC1A · merosin-deficient congenital muscular dystrophy · merosin-deficient congenital muscular dystrophy type 1A · merosin-negative congenital muscular dystrophy · muscular dystrophy, congenital merosin-deficient, 1A · muscular dystrophy, congenital merosin-deficient, type 1A · muscular dystrophy, congenital, merosin deficient or partially deficient · muscular dystrophy, congenital, merosin-deficient

Data availability: 781 ClinVar variants · 4 GenCC gene-disease records · 34 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy › congenital merosin-deficient muscular dystrophy 1A

Related subtypes (22): Ullrich congenital muscular dystrophy, Bethlem myopathy, arthrogryposis due to muscular dystrophy, congenital muscular dystrophy-infantile cataract-hypogonadism syndrome, muscular dystrophy, congenital, with rapid progression, congenital myasthenic syndrome 10, megaconial type congenital muscular dystrophy, congenital muscular dystrophy 1B, congenital muscular dystrophy due to integrin alpha-7 deficiency, congenital muscular dystrophy due to LMNA mutation, congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, congenital myopathy, Paradas type, autosomal recessive myogenic arthrogryposis multiplex congenita, muscular dystrophy-dystroglycanopathy, congenital muscular dystrophy with hyperlaxity, muscle-eye-brain disease, rigid spine syndrome, congenital muscular dystrophy with cataracts and intellectual disability, SNUPN-related muscular dystrophy with or without multi-system involvement, congenital muscular dystrophy caused by variation in POMGNT2, collagen 6-related congenital muscular dystrophy, congenital muscular dystrophy without intellectual disability

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

234 likely pathogenic, 103 pathogenic, 97 uncertain significance, 68 pathogenic/likely pathogenic, 63 conflicting classifications of pathogenicity, 20 likely benign, 8 benign/likely benign, 6 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
190218	NM_000426.3(LAMA2):c.[2461A>C;8282T>C]		Pathogenic	no assertion criteria provided
424784	NM_000426.3(LAMA2):c.[2049_2050delAG];[523G>T]		Pathogenic	criteria provided, single submitter
1028256	NM_000426.4(LAMA2):c.7898+1G>A	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1031567	NM_000426.4(LAMA2):c.3186C>A (p.Cys1062Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1066222	NM_000426.4(LAMA2):c.3037+1G>T	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070781	NM_000426.4(LAMA2):c.8748del (p.Glu2917fs)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1072865	NM_000426.4(LAMA2):c.5602G>T (p.Glu1868Ter)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076694	NM_000426.4(LAMA2):c.1852G>T (p.Glu618Ter)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1173099	NM_000426.4(LAMA2):c.908dup (p.Asn303fs)	LAMA2	Pathogenic	criteria provided, single submitter
1174129	NM_000426.4(LAMA2):c.4996C>T (p.Gln1666Ter)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180611	NM_000426.4(LAMA2):c.250C>T (p.Arg84Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1236199	NM_000426.4(LAMA2):c.7778del (p.Gly2593fs)	LAMA2	Pathogenic	criteria provided, single submitter
1236200	NM_000426.4(LAMA2):c.8380_8383del (p.Arg2794fs)	LAMA2	Pathogenic	criteria provided, single submitter
1299245	NM_000426.4(LAMA2):c.3938del (p.Tyr1313fs)	LAMA2	Pathogenic	criteria provided, single submitter
1299246	NM_000426.4(LAMA2):c.4058+1G>A	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1323163	NM_000426.4(LAMA2):c.442dup (p.Arg148fs)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1332702	NM_000426.4(LAMA2):c.1282_1283dup (p.Asp429fs)	LAMA2	Pathogenic	criteria provided, single submitter
1333597	NM_000426.4(LAMA2):c.5085dup (p.Ala1696fs)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1355480	NM_000426.4(LAMA2):c.938_939del (p.Thr313fs)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1363194	NM_000426.4(LAMA2):c.872del (p.Gly291fs)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14290	NM_000426.4(LAMA2):c.3718C>T (p.Gln1240Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
14291	NM_000426.4(LAMA2):c.9253C>T (p.Arg3085Ter)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14292	NM_000426.4(LAMA2):c.8265del (p.Glu2756fs)	LAMA2	Pathogenic	no assertion criteria provided
14296	NM_000426.4(LAMA2):c.7732C>T (p.Arg2578Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
14299	NM_000426.4(LAMA2):c.4645C>T (p.Arg1549Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
14300	NM_000426.4(LAMA2):c.7147C>T (p.Arg2383Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
14301	NM_000426.4(LAMA2):c.2901C>A (p.Cys967Ter)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
14302	NM_000426.4(LAMA2):c.825del (p.Tyr276fs)	LAMA2	Pathogenic	no assertion criteria provided
14303	NM_000426.4(LAMA2):c.7750-1713_7899-2153del	LAMA2	Pathogenic	no assertion criteria provided
1431215	NM_000426.4(LAMA2):c.7870_7871dup (p.Ser2625fs)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LAMA2	Definitive	Autosomal recessive	congenital merosin-deficient muscular dystrophy 1A	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMA2	Orphanet:258	Laminin subunit alpha 2-related congenital muscular dystrophy
LAMA2	Orphanet:565837	Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LAMA2	HGNC:6482	ENSG00000196569	P24043	Laminin subunit alpha-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMA2	Laminin subunit alpha-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMA2	Other/Unknown	no		Laminin_IV, EGF, Laminin_G

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
mucosa of stomach	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMA2	272	ubiquitous	marker	mucosa of stomach, calcaneal tendon, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA2	2,688

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LAMA2	P24043	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET promotes cell motility	1	601.0×	0.007	LAMA2
Attachment of bacteria to epithelial cells	1	496.5×	0.007	LAMA2
Laminin interactions	1	380.7×	0.007	LAMA2
MET activates PTK2 signaling	1	380.7×	0.007	LAMA2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.007	LAMA2
Signaling by MET	1	317.2×	0.007	LAMA2
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.007	LAMA2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	LAMA2
Non-integrin membrane-ECM interactions	1	154.3×	0.010	LAMA2
ECM proteoglycans	1	150.3×	0.010	LAMA2
Extracellular matrix organization	1	63.1×	0.022	LAMA2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.024	LAMA2
Nervous system development	1	42.9×	0.027	LAMA2
Developmental Biology	1	14.5×	0.074	LAMA2
Signal Transduction	1	10.2×	0.098	LAMA2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of synaptic transmission, cholinergic	1	3370.4×	0.002	LAMA2
regulation of basement membrane organization	1	2808.7×	0.002	LAMA2
Schwann cell differentiation	1	2407.4×	0.002	LAMA2
positive regulation of integrin-mediated signaling pathway	1	1296.3×	0.002	LAMA2
positive regulation of muscle cell differentiation	1	1123.5×	0.002	LAMA2
maintenance of blood-brain barrier	1	481.5×	0.004	LAMA2
regulation of embryonic development	1	330.4×	0.005	LAMA2
positive regulation of cell adhesion	1	271.8×	0.006	LAMA2
muscle organ development	1	166.8×	0.008	LAMA2
regulation of cell migration	1	157.5×	0.008	LAMA2
axon guidance	1	90.6×	0.012	LAMA2
cell adhesion	1	37.5×	0.027	LAMA2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LAMA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LAMA2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LAMA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 8.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06132750	Not specified	RECRUITING	A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.
NCT06354790	Not specified	RECRUITING	Natural History Study of Children With LAMA2-related Dystrophies
NCT06924125	Not specified	RECRUITING	Spanish Natural History Study for LAMA2 Muscular Dystrophy
NCT07125040	Not specified	RECRUITING	Characterization of the Natural History of LAMA2-RD and Identification of Novel Disease Biomarkers
NCT03970135	Not specified	COMPLETED	Fat and Glucose Metabolism in Fed and Fasted State in Patients With Low Skeletal Muscle Mass
NCT04299321	Not specified	COMPLETED	Retrospective Natural History Study of Infants and Toddlers With LAMA2-CMD
NCT04478981	Not specified	COMPLETED	The Natural History of Patients With Mutations in SEPN1 (SELENON) or LAMA2
NCT06582537	Not specified	COMPLETED	LAMA2 Genetic Correction