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Huntington disease-like 2(HDL2)

MedGen UID:
341120
Concept ID:
C1847987
Disease or Syndrome
Synonym: HDL2
SNOMED CT: Huntington disease-like 2 (721228006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): JPH3 (16q24.2)
 
Monarch Initiative: MONDO:0011671
OMIM®: 606438
Orphanet: ORPHA98934

Disease characteristics

Excerpted from the GeneReview: Huntington Disease-Like 2
Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities which lead to death within ten to 20 years. HDL2 cannot be differentiated from Huntington disease clinically. Neurologic abnormalities include chorea, hypokinesia (rigidity, bradykinesia), dysarthria, and hyperreflexia in the later stages of the disease. There is a strong correlation between the duration of the disease and the progression of the motor and cognitive disorder. [from GeneReviews]
Authors:
David G Anderson  |  Amanda Krause  |  Russell L Margolis   view full author information

Additional description

From MedlinePlus Genetics
HDL3 begins much earlier in life than the other HDLs (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has some different signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDLs.

HDL1, HDL2, and HDL4 usually begin in early to mid-adulthood, although they can start earlier or later. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements (dyskinesia), poor coordination, and trouble learning new information or making decisions. Many people with an HDL develop involuntary jerking or twitching movements known as chorea. Over time, these abnormal movements worsen. Affected individuals may develop problems with walking (bradykinesia), speaking (dysarthria), and swallowing (dysphagia). People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities (dementia). Individuals with an HDL syndrome can live for 10 to 20 years after signs and symptoms begin, though this can vary between the types of HDL syndromes.

Huntington's disease-like (HDL) is a group of related neurological conditions. As the name suggests, HDLs resembles Huntington's disease. HDLs and Huntington's disease are both characterized by uncontrolled movements, emotional problems, and loss of thinking ability. In both conditions these signs and symptoms worsen over time. HDLs occurs in people with the characteristic features of Huntington's disease who do not have a variant (also called mutation) in the gene typically associated with that disorder. Researchers have described four HDLs that are designated Huntington's disease-like 1 (HDL1) through Huntington's disease-like 4 (HDL4). Sometimes, HDL4 is also known as spinocerebellar ataxia type 17 (SCA17).  https://medlineplus.gov/genetics/condition/huntingtons-disease-like

Clinical features

From HPO
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Delusion
MedGen UID:
3715
Concept ID:
C0011253
Mental or Behavioral Dysfunction
A delusion is a fixed false belief held despite evidence to the contrary. The term delusion broadly encompasses all false judgments that possess the following external characteristics to a significant, albeit unspecified, extent
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hallucinations
MedGen UID:
6709
Concept ID:
C0018524
Mental or Behavioral Dysfunction
Perceptions in a conscious and awake state that, in the absence of external stimuli, have qualities of real perception. These perceptions are vivid, substantial, and located in external objective space.
Apathy
MedGen UID:
39083
Concept ID:
C0085632
Mental or Behavioral Dysfunction
Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Bradykinesia
MedGen UID:
115925
Concept ID:
C0233565
Sign or Symptom
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Action tremor
MedGen UID:
65875
Concept ID:
C0234376
Sign or Symptom
A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Inertia
MedGen UID:
868183
Concept ID:
C4022575
Finding
Reduction of goal-directed behaviors linked to the impairment in frontal executive functions (planning of an action for example).
Subcortical dementia
MedGen UID:
870488
Concept ID:
C4024935
Disease or Syndrome
A particular type of dementia characterized by a pattern of mental defects consisting prominently of forgetfulness, slowness of thought processes, and personality or mood change.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHuntington disease-like 2
Follow this link to review classifications for Huntington disease-like 2 in Orphanet.

Recent clinical studies

Etiology

Ferreira-Correia A, Krause A, Anderson DG
J Huntingtons Dis 2020;9(4):325-334. doi: 10.3233/JHD-200422. PMID: 33044188
Ferreira-Correia A, Anderson DG, Cockcroft K, Krause A
Neuropsychologia 2020 Jan;136:107238. Epub 2019 Nov 5 doi: 10.1016/j.neuropsychologia.2019.107238. PMID: 31704316
Peikert K, Danek A, Hermann A
Eur J Med Genet 2018 Nov;61(11):699-705. Epub 2017 Dec 16 doi: 10.1016/j.ejmg.2017.12.007. PMID: 29253590
Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Danek A
Neurology 2007 Jan 9;68(2):92-8. doi: 10.1212/01.wnl.0000250356.78092.cc. PMID: 17210889

Diagnosis

Narotam-Jeena H, Guttman M, van Hillegondsberg L, van Coller R, Krause A, Carr J
Mov Disord Clin Pract 2024 Jul;11(7):850-854. Epub 2024 May 9 doi: 10.1002/mdc3.14052. PMID: 38725192Free PMC Article
Walker RH, Gatto EM, Bustamante ML, Bernal-Pacheco O, Cardoso F, Castilhos RM, Chana-Cuevas P, Cornejo-Olivas M, Estrada-Bellmann I, Jardim LB, López-Castellanos R, López-Contreras R, Maia DP, Mazzetti P, Miranda M, Rodríguez-Violante M, Teive H, Tumas V
Parkinsonism Relat Disord 2018 Aug;53:10-20. Epub 2018 May 21 doi: 10.1016/j.parkreldis.2018.05.021. PMID: 29853295
Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Castilhos RM, Souza AF, Furtado GV, Gheno TC, Silva AL, Vargas FR, Lima MA, Barsottini O, Pedroso JL, Godeiro C Jr, Salarini D, Pereira ET, Lin K, Toralles MB, Saute JA, Rieder CR, Quintas M, Sequeiros J, Alonso I, Saraiva-Pereira ML, Jardim LB
Clin Genet 2014 Oct;86(4):373-7. Epub 2013 Oct 17 doi: 10.1111/cge.12283. PMID: 24102565
Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Danek A
Neurology 2007 Jan 9;68(2):92-8. doi: 10.1212/01.wnl.0000250356.78092.cc. PMID: 17210889

Prognosis

Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Danek A
Neurology 2007 Jan 9;68(2):92-8. doi: 10.1212/01.wnl.0000250356.78092.cc. PMID: 17210889

Clinical prediction guides

Narotam-Jeena H, Guttman M, van Hillegondsberg L, van Coller R, Krause A, Carr J
Mov Disord Clin Pract 2024 Jul;11(7):850-854. Epub 2024 May 9 doi: 10.1002/mdc3.14052. PMID: 38725192Free PMC Article
Ferreira-Correia A, Anderson DG, Cockcroft K, Krause A
Appl Neuropsychol Adult 2022 Mar-Apr;29(2):223-233. Epub 2020 Mar 9 doi: 10.1080/23279095.2020.1734810. PMID: 32149528
Ferreira-Correia A, Krause A, Anderson DG
J Huntingtons Dis 2020;9(4):325-334. doi: 10.3233/JHD-200422. PMID: 33044188
Den Dunnen WFA
Handb Clin Neurol 2017;145:383-391. doi: 10.1016/B978-0-12-802395-2.00027-4. PMID: 28987184
Walker RH, Jung HH, Dobson-Stone C, Rampoldi L, Sano A, Tison F, Danek A
Neurology 2007 Jan 9;68(2):92-8. doi: 10.1212/01.wnl.0000250356.78092.cc. PMID: 17210889

Recent systematic reviews

Anderson DG, Walker RH, Connor M, Carr J, Margolis RL, Krause A
J Huntingtons Dis 2017;6(1):37-46. doi: 10.3233/JHD-160232. PMID: 28339400

Supplemental Content