Table 2a.

Selected Genes of Interest in the Differential Diagnosis of MDC1A

Gene(s)DisorderMOIDistinguishing Clinical Features 1
B3GALNT2
B4GAT1
CRPPA
DAG1
FKRP
FKTN
GMPPB
LARGE1
POMGNT1
POMGNT2
POMK
POMT1
POMT2
RXYLT1 		Dystroglycanopathies, congenital (OMIM PS236670)ARWide variety of brain & eye structural & functional abnormalities (may be more severe in Walker Warburg syndrome & muscle-eye-brain disease)
COL6A1
COL6A2
COL6A3 		Collagen type VI disorders (Ullrich CMD) 2AR 3Characterized by triad of myopathic features, hyperlaxity, & typical skin changes (keratosis pilaris, keloids, striae)
BIN1
CCDC78
DNM2
MAP3K20
MTM1
MTMR14
SPEG 		Centronuclear/myotubular myopathy 4 (See X-Linked Myotubular Myopathy.)XL
AR
AD		Ophthalmoplegia; facial bulbar weakness
ACTA1
CFL2
KBTBD13
KLHL40
KLHL41
LMOD3
NEB
TNNT1
TPM2
TPM3 		Nemaline myopathy 4 (OMIM PS161800)AR
AD		Facial & bulbar weakness
RYR1 Central core disease (OMIM 117000) &
multiminicore disease (OMIM 255320) 4		AR
AD 5		Malignant hyperthermia in some affected individuals
SELENON Congenital myopathy w/fiber-type disproportionAD
AR		Insulin resistance
Rigid spine (congenital) muscular dystrophy (OMIM 602771)ARRestrictive respiratory syndrome (nocturnal hypoventilation)
CHAT
CHRNE
COLQ
DOK7
GFPT1
RAPSN 6		 Congenital myasthenic syndromes AR
AD		Facial & bulbar weakness; striking motor variability; decremental EMG response or abnormal single-fiber EMG
SMN1 7 Spinal muscular atrophy ARRelatively rapid motor impairment & tongue fasciculations; EMG & muscle biopsy findings suggest denervation-reinnervation profile; normal nerve conduction studies

AD = autosomal dominant; AR = autosomal recessive; CMD = congenital muscular dystrophy; MOI = mode of inheritance; XL = X-linked

1.

In addition to absence of brain white matter changes

2.

Immunohistochemical analysis of muscle or skin biopsies can be diagnostically useful, showing variable reduction of antibody labeling against collagen VI or glycosylated α-dystroglycan.

3.

The Ullrich congenital muscular dystrophy phenotype is usually inherited in an autosomal recessive manner; however, exceptions occur.

4.

Selected examples of congenital myopathies are included in Table 2a; other congenital myopathies may also be relevant to the differential diagnosis of MDC1A.

5.

Minicore disease is most often inherited in an autosomal recessive manner. The report of minicore disease in two generations in a few families also suggested autosomal dominant inheritance.

6.

Most commonly associated of ~30 known genes; pathogenic variants in one of multiple genes encoding proteins expressed at the neuromuscular junction are currently known to be associated with subtypes of congenital myasthenic syndromes.

7.

The detection of the genetic defect causing spinal muscular atrophy (deletion involving SMN1 exons 7 and 8) requires specific methodologies.

From: LAMA2 Muscular Dystrophy

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