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Huntington Disease-Like 2

Abstract
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.The diagnosis of HDL2 rests on positive family history, characteristic clinical findings, and the detection of an expansion of 40 or more CTG trinucleotide repeats in JPH3.Treatment of manifestations: Treatment is symptomatic and is presumably similar to that for HD and other neurodegenerative disorders – although this must be considered speculative pending objective data. Pharmacologic agents that may suppress abnormal movements include tetrabenazine and its derivatives, low-dose neuroleptic agents such as fluphenazine and haloperidol. Antidepressants, antipsychotics, mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine), and occasionally stimulants may improve psychiatric manifestations. Education about the course of disease and environmental interventions (regular schedules, use of lists to assist memory). Remove loose rugs and clutter from the individual's home and minimize or eliminate the need for stairs to help prevent falls and other injuries; driving may need to be curtailed or limited to prevent risk of accidents; food should be prepared in such a manner as to prevent choking. Surveillance: Monitor: nutrition and swallowing in order to implement feeding changes when necessary to minimize risk of aspiration; gait and use appropriate strategies or devices to minimize falls; driving to assure that affected individuals do not present a danger to themselves or others; mood and irritability, such that measures to decrease the risk of suicide, other behavioral abnormalities, and distress may be implemented. Agents/circumstances to avoid: Any agents that increase ataxia should be used with caution; avoid polypharmacy, which may exacerbate delirium.HDL2 is inherited in an autosomal dominant manner. HDL2 resulting from a de novo pathogenic variant has not been reported but is theoretically possible. Offspring of an individual with HDL2 have a 50% chance of inheriting the HDL2-causing allele. Predictive testing in asymptomatic adults at risk is available but requires careful thought (including pre- and post-test genetic counseling) as there is currently no cure for the disorder. Predictive testing is not considered appropriate for asymptomatic at-risk individuals younger than age 18 years. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible once an HDL2-causing expansion has been identified in an affected family member.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Publisher

University of Washington, Seattle
Seattle (WA)

Language

eng

PubMed ID

20301701

Citation

Anderson DG, Krause A, Margolis RL: Huntington Disease-Like 2.GeneReviews®. Edited by Adam MP, et al: University of Washington, Seattle, 1993, Seattle (WA).
Anderson DG, Krause A, Margolis RL. Huntington Disease-Like 2. Edited by Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
Anderson DG & Krause A & Margolis RL. (1993). Huntington Disease-Like 2. Edited by Adam MP & Ardinger HH & Pagon RA, et al. In GeneReviews®. Seattle (WA): University of Washington, Seattle;
Anderson DG, Krause A, Margolis RL. Edited by Adam MP, et al. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Huntington Disease-Like 2 BT - GeneReviews® A1 - Anderson,David G, AU - Krause,Amanda, AU - Margolis,Russell L, Y1 - 1993/// PY - 2019/6/27/pubmed PY - 2019/6/27/medline PY - 2010/3/20/entrez KW - Junctophilin-3 KW - JPH3 KW - Huntington Disease-Like 2 N2 - CLINICAL CHARACTERISTICS: 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. DIAGNOSIS/TESTING: The diagnosis of HDL2 rests on positive family history, characteristic clinical findings, and the detection of an expansion of 40 or more CTG trinucleotide repeats in JPH3. MANAGEMENT: Treatment of manifestations: Treatment is symptomatic and is presumably similar to that for HD and other neurodegenerative disorders – although this must be considered speculative pending objective data. Pharmacologic agents that may suppress abnormal movements include tetrabenazine and its derivatives, low-dose neuroleptic agents such as fluphenazine and haloperidol. Antidepressants, antipsychotics, mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine), and occasionally stimulants may improve psychiatric manifestations. Education about the course of disease and environmental interventions (regular schedules, use of lists to assist memory). Remove loose rugs and clutter from the individual's home and minimize or eliminate the need for stairs to help prevent falls and other injuries; driving may need to be curtailed or limited to prevent risk of accidents; food should be prepared in such a manner as to prevent choking. Surveillance: Monitor: nutrition and swallowing in order to implement feeding changes when necessary to minimize risk of aspiration; gait and use appropriate strategies or devices to minimize falls; driving to assure that affected individuals do not present a danger to themselves or others; mood and irritability, such that measures to decrease the risk of suicide, other behavioral abnormalities, and distress may be implemented. Agents/circumstances to avoid: Any agents that increase ataxia should be used with caution; avoid polypharmacy, which may exacerbate delirium. GENETIC COUNSELING: HDL2 is inherited in an autosomal dominant manner. HDL2 resulting from a de novo pathogenic variant has not been reported but is theoretically possible. Offspring of an individual with HDL2 have a 50% chance of inheriting the HDL2-causing allele. Predictive testing in asymptomatic adults at risk is available but requires careful thought (including pre- and post-test genetic counseling) as there is currently no cure for the disorder. Predictive testing is not considered appropriate for asymptomatic at-risk individuals younger than age 18 years. Prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible once an HDL2-causing expansion has been identified in an affected family member. PB - University of Washington, Seattle CY - Seattle (WA) UR - https://www.unboundmedicine.com/medline/citation/20301701/GeneReviews®:_Huntington_Disease-Like_2 L2 - https://www.ncbi.nlm.nih.gov/books/NBK1529 DB - PRIME DP - Unbound Medicine ER -