Abstract
2007 Aug 23 [updated 2026 Mar 25]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026.
ABSTRACT
CLINICAL CHARACTERISTICS: CHMP2B-related frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) is characterized most frequently by FTD with subtle personality changes and slowly progressive behavioral changes, dysexecutive syndrome, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. Individuals can also have features of ALS, a combined phenotype of FTD-ALS, or atypical phenotypes. Onset is typically between ages 46 and 65 years. Additional features of asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs may be related to treatment with neuroleptic drugs. Clinical manifestations and disease course are highly variable. Disease duration may be as short as three years or longer than 20 years.
DIAGNOSIS/TESTING: The diagnosis of CHMP2B-FTD-ALS is established in a proband with suggestive findings and a heterozygous pathogenic variant in CHMP2B identified by molecular genetic testing.
MANAGEMENT: Treatment of manifestations: Environmental, behavioral, and physical interventions to minimize undesired behaviors; counseling for affective disorders; selective serotonin reuptake inhibitors for affective disorders or disinhibition; serotonin and noradrenaline reuptake inhibitors for prominent apathy; atypical antipsychotics may improve physical aggressiveness. Administered antipsychotics should be reevaluated at short intervals with the goal of discontinuation as soon as feasible. Cognitive rehabilitation; management of motor neuron involvement per physical medicine and rehabilitation, occupational therapy, and physical therapy; spasmolytics for severe spasticity; psychosocial support, education, and discussion of advanced care planning.
Surveillance: At least annual neurologic examination with evaluation for behavioral and psychiatric manifestations; screening evaluation for cognitive function; physical medicine and rehabilitation and physical therapy evaluation of mobility; physical and occupational therapy evaluation of activities of daily living; assessment of caregiver and social work needs; EEG if seizures are suspected.
GENETIC COUNSELING: CHMP2B-FTD-ALS is inherited in an autosomal dominant manner. Penetrance is age dependent and appears to be nearly complete. Almost all individuals diagnosed with CHMP2B-FTD-ALS have an affected parent. Each child of an individual with CHMP2B-FTD-ALS has a 50% chance of inheriting the pathogenic variant. Once the CHMP2B pathogenic variant has been identified in an affected family member, predictive testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.