Clinical Guidance

BSCL2-related neurologic disorders affect both the lower and upper motor neurons. Detailed clinical and electrophysiologic studies in 90 individuals with the pathogenic variant showed incomplete penetrance, clinical intrafamilial variability with several phenotypic subtypes being reported (even within the same family), and broad variation in disease severity, suggesting a subdivision into the following six main phenotypes (subtypes 1-6), all of which can be seen in the same family . Subtype 1. No signs or symptoms. No clinical or electrophysiologic abnormalities are present. Subtype 2. Clinical signs but no symptoms. Suggestive clinical signs include foot deformity, mild asymmetric thenar wasting, brisk lower-limb deep-tendon reflexes (DTRs), and/or electrophysiologic abnormalities.

Source: GeneReviews — "BSCL2-Related Neurologic Disorders/ Seipinopathy"

Penetrance

Reduced penetrance for BSCL2-related neurologic disorders has been shown by and . A detailed genotype-phenotype correlation study in 90 individuals with the pathogenic variant demonstrated that 24.4% of individuals with the variant remained asymptomatic (subtype 1) or were only subclinically affected (subtype 2) .

Source: GeneReviews — "BSCL2-Related Neurologic Disorders/ Seipinopathy"

Differential Diagnosis

Hereditary disorders to consider in the differential diagnosis for subtypes of BSCL2-related neurologic disorder. Other types of axonal neuropathies (see Charcot-Marie-Tooth Hereditary Neuropathy Overview), variants of amyotrophic lateral sclerosis (ALS), or hereditary spastic paraplegia may mimic BSCL2-related neurologic disorder subtypes:

• Subtype 3.

GARS1-associated axonal neuropathy caused by pathogenic variants in GARS1 and inherited in an autosomal dominant manner

• Subtype 4

• ALS4 (juvenile-onset motor neuron disease) caused by pathogenic variants in SETX and inherited in an autosomal dominant manner (See ALS Overview.)

• SPG3A, caused by pathogenic variants in ATL1 and typically inherited in an autosomal dominant manner

• Subtype 5

Source: GeneReviews — "BSCL2-Related Neurologic Disorders/ Seipinopathy"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "BSCL2-Related Neurologic Disorders/ Seipinopathy"