Table 4.

Inherited Conditions to Consider in the Differential Diagnosis of Huntington Disease

DisorderGene(s)MOIClinical Features of the Disorder
Overlapping w/HDDistinguishing from HD
Frontotemporal dementia &/or amyotrophic lateral sclerosis C9orf72 AD
  • Movement disorders
  • Dementia
  • Psychiatric disturbances
  • Myoclonus
  • Tremor
  • Torticollis
Huntington disease-like 1 (HDL1) (OMIM 603218) 1 PRNP ADRange of clinical features that overlap w/HD
  • Early onset
  • Slow progression
Huntington disease-like 2 (HDL2) JPH3 ADClinically indistinguishable from HDPrevalence highest among & perhaps exclusive to individuals of African descent
Chorea-acanthocytosis (ChAc) VPS13A AR
  • Progressive movement disorder
  • Progressive cognitive & behavior changes
  • Myopathy
  • ↑ serum CK
  • Acanthocytosis
  • Seizures common
  • Mean age of onset ~30 yrs
McLeod neuroacanthocytosis syndrome (MLS) XK XL
  • Cognitive impairment
  • Psychiatric symptoms
  • Acanthocytosis
  • Compensated hemolysis
  • McLeod blood group phenotype
Spinocerebellar ataxia type 17 (SCA17) TBP AD
  • Chorea
  • Dementia
  • Psychiatric disturbances
Cerebellar ataxia is the prominent movement disorder.
Dentatorubral-pallidoluysian atrophy (DRPLA) ATN1 AD
  • Progressive movement disorders & dementia
  • Psychiatric disturbances
Ataxia & myoclonus are prominent movement disorders.
Benign hereditary chorea (OMIM 118700) NKX2-1 ADChorea
  • Nonprogressive chorea
  • Not assoc w/dementia
Hereditary cerebellar ataxia (See Hereditary Ataxia Overview.)ManyAD
AR
XL		Movement disorderHereditary cerebellar ataxia assoc w/prominent cerebellar & long tract signs
Familial Creutzfeld-Jakob disease (fCJD) (See Genetic Prion Disease.) PRNP AD
  • Typically late onset
  • Progressive dementia
  • Movement disorders
  • Behavior changes
  • Psychiatric symptoms
  • fCJD progresses more rapidly.
  • Myoclonus is a prominent involuntary movement.
Early-onset familial Alzheimer disease APP
PSEN1
PSEN2 		ADDementiaNo movement disorders
Familial frontotemporal dementia with parkinsonism-17 MAPT AD
  • Late onset
  • Progressive movement disorders, dementia, & behavior changes
  • Psychiatric disturbances
No chorea

AD = autosomal dominant; AR = autosomal recessive; CNS = central nervous system; MOI = mode of inheritance; XL = X-linked

1.

HDL1 is caused by a specific pathogenic variant (8 extra octapeptide repeats) in the prion protein gene, PRNP, on chromosome 20p [Laplanche et al 1999, Moore et al 2001]. Similar pathogenic variants at this locus also result in other forms of prion disease such as familial Creutzfeldt-Jakob disease.

From: Huntington Disease

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