Table 2.

Genes of Interest in the Differential Diagnosis of Spinal and Bulbar Muscular Atrophy

Gene(s)DisorderMOIClinical FeaturesComment
~30 genes 1 incl:
C9orf72
SOD1
FUS
TARDBP
Amyotrophic lateral sclerosis (ALS)AD
AR
Involves upper & lower motor neurons; upper motor neuron signs incl hyperreflexia & spasticity.Differentiation of ALS from SBMA can usually be made based on history & physical exam. Persons w/ALS typically show involvement of wider range of muscle groups & more rapid disease progression. An important feature of SBMA is androgen insensitivity (often causing gynecomastia); thus, eval of males w/motor neuron disease should incl exam for gynecomastia. 2
SMN1 Adult-onset spinal muscular atrophy (SMA IV) 3ARTypically presents w/muscle weakness in 2nd or 3rd decade. Specific pattern of muscle involvement: weakness disproportionately affects deltoids, triceps, & quadriceps. Cardiac & cognitive functioning normal. If loss of ambulation occurs, may be after 5th decade.Unlike SBMA, SMA IV is not assoc w/gradual progression, gynecomastia, testicular atrophy, or ↓ fertility.
>80 genes incl:
GDAP1
GJB1
HINT1
MFN2
MPZ
PMP22
SH3TC2
SORD
Charcot-Marie-Tooth hereditary neuropathy (CMT)AD
AR
XL
Prominent sensory findings in addition to muscle weaknessPersons w/CMT do not have lower motor neuron disease findings, esp tremors or fasciculations. Also, males w/CMT do not develop signs of androgen insensitivity.

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SBMA = spinal and bulbar muscular atrophy; XL = X-linked

1.

It is estimated that 10% of individuals with ALS have at least one family member with ALS. The identified ALS-related genes may account for at least half of ALS that occurs in families with a history of more than one affected individual. Thirty genes have been implicated in ALS; of these, C9orf72, FUS, SOD1, and TARDBP are the most commonly associated genes.

2.
3.

SMA IV is the least common form of SMA and affects fewer than 5% of individuals with SMA.

From: Spinal and Bulbar Muscular Atrophy

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