Table 2.

Early-Onset Muscle Disorders to Consider in the Differential Diagnosis of Salih Myopathy

DisorderGene(s)MOIClinical Features
Overlapping w/Salih myopathyDistinguishing from Salih myopathy
Spinal muscular atrophy (SMA) SMN1 AR
  • Early-onset muscle weakness (age 6-12 mos) (SMA II)
  • Weakness → frequent falling & difficulty walking up & down stairs (SMA III)
  • Normal intelligence
  • Onset age: >12 mos (SMA III)
  • Frequent finger trembling
  • Sparing of facial muscles
  • Serum CK: normal
  • EKG: frequent background tremors but no cardiac involvement
  • EMG: neurogenic features (polyphasic waves, positive sharp waves & fibrillations) (versus myopathic EMG features seen in Salih myopathy)
  • Skeletal muscle histology: group atrophy of type 1 & type 2 muscle fibers (vs type 1 fiber predominance seen in Salih myopathy)
Duchenne muscular dystrophy DMD XL
  • Usually manifests in early childhood w/delayed milestones
  • Subclinical or clinical cardiac involvement presents in majority of affected individuals
  • Serum CK: ↑ (>10-300x normal)
  • EKG: characteristic pattern
  • Skeletal muscle histology: established dystrophic morphology early in childhood
  • Immunohistochemical staining of skeletal muscle: negative for dystrophin
Sarcoglycanopathies 1 SGCA
SGCB
SGCG
SGCD 		AR
  • Onset age: 3-15 yrs
  • In some, delayed walking & frequent falling
  • Cardiomyopathy
  • EKG: left anterior fascicular block
  • Serum CK: ↑ (10-70x normal)
  • EKG: tall R wave in V1 & V2 (vs Salih myopathy, in which deep S waves are seen in the right precordial leads assoc w/↓ R/S ratio; see Figure 1.)
  • Echocardiogram: left ventricular dysfunction associated w/regional wall motion abnormalities (e.g., inferior wall & posterior septum hypokinesia) (vs Salih myopathy, in which the contractile dysfunction & dilatation, initially restricted to the left ventricle, subsequently affects all chambers)
  • Skeletal muscle histology: dystrophic early in disease course
  • Immunohistochemical staining of skeletal muscle: negative staining for ≥1 of the sarcoglycans α (adhalin), β, γ, & δ
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C5 (previously LGMD2I; OMIM 607155) FKRP AR
  • Onset age: <1 yr
  • In some, infantile cardiomyopathy
  • Muscle weakness & calf muscle hypertrophy
  • Skeletal muscle histology: in some, mild myopathic features (but significantly ↓ signal w/α-dystroglycan on immunostaining)
  • Absence of ptosis
  • Serum CK: elevated
  • EKG: dysmorphic notched P-waves, complete or incomplete right BBB or incomplete left BBB, & Q waves in lateral leads
LGMD2J TTN ARSee Genetically Related Disorders.See Genetically Related Disorders.
Fukuyama CMD FKTN AR
  • Muscle weakness typically begins at birth or in early infancy.
  • Children present w/delay or arrest of gross motor development.
  • Dilated cardiomyopathy
  • Intellectual disability
  • Epilepsy
  • Variable eye malformations
  • Brain MRI: central nervous system malformations
LAMA2-related muscular dystrophy LAMA2 AR
  • Congenital hypotonia
  • Delayed or arrested motor milestones
  • Progressive diffuse joint contractures
  • Spinal rigidity
  • Normal cognitive abilities in majority of affected individuals
  • ~1/3 of individuals develop left ventricular dysfunction
  • Myopathic facies
  • ± calf muscle hypertrophy
  • Brain MRI: diffuse white matter signal abnormalities
  • Immunohistochemical staining of skeletal muscle: total or partial merosin deficiency
LMNA-related CMD (OMIM 613205) LMNA AD
  • Infantile hypotonia & weakness of axial-cervical muscles
  • Dilated cardiomyopathy
  • Facial weakness
  • Ptosis
  • Muscle pseudohypertrophy
Classic multiminicore disease (OMIM 606210, 180901) RYR1
SELENON 		AR
(AD)
  • Neonatal hypotonia & early-onset delayed motor development
  • Weakness of trunk & neck flexors > pelvic & shoulder girdle muscles
  • Individuals usually ambulatory
  • Facial muscle weakness ranging from absent to severe
  • Serum CK: may be slightly ↑.
  • Similar skeletal muscle histology
  • Major respiratory involvement requiring respiratory support
  • Cardiac involvement (right ventricular failure, cardiomyopathy) secondary to respiratory impairment

AD = autosomal dominant; AR = autosomal recessive; BBB = bundle branch block; CMD = congenital muscular dystrophy; EMG = electromyography; LGMD = limb-girdle muscular dystrophy; MOI = mode of inheritance; XL = X linked

1.

From: Salih Myopathy

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