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
Gene(s) | Disorder | MOI | Distinguishing Clinical Features1 |
|---|
RXYLT1 | Dystroglycanopathies, congenital (OMIM PS236670) | AR | Wide 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)2 | AR3 | Characterized by triad of myopathic features, hyperlaxity, typical skin changes (keratosis pilaris, keloids, striae) BIN1 CCDC78 DNM2 MAP3K20 MTM1 MTMR14 |
SPEG | Centronuclear/myotubular myopathy4 (See X-Linked Myotubular Myopathy.) | XLARAD | Ophthalmoplegia; facial bulbar weakness ACTA1 CFL2 KBTBD13 KLHL40 KLHL41 LMOD3 NEB TNNT1 TPM2 |
TPM3 | Nemaline myopathy4 (OMIM PS161800) | ARAD | Facial bulbar weakness |
RYR1 | Central core disease (OMIM 117000) multiminicore disease (OMIM 255320)4 | ARAD5 | Malignant hyperthermia in some affected individuals |
SELENON | Congenital myopathy w/fiber-type disproportion | ADAR | Insulin resistance |
Rigid spine (congenital) muscular dystrophy (OMIM 602771) | AR | Restrictive respiratory syndrome (nocturnal hypoventilation) CHATCHRNECOLQDOK7GFPT1RAPSN6 | — |
Congenital myasthenic syndromes | ARAD | Facial bulbar weakness; striking motor variability; decremental EMG response or abnormal single-fiber EMG SMN17 | — |
Spinal muscular atrophy | AR | Relatively 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 ... | — |
Source: GeneReviews — "LAMA2 Muscular Dystrophy"
