[MIM 143 100]

(Huntington's chorea)

Prevalence estimated at 5/100,000. Autosomal dominant transmission with variable penetrance. Mutation of the HTT gene (4p16.3), coding for huntingtin. This gene contains a number of CAG trinucleotide repeats. The normal number of repeats varies from 6 to 35. The adult form of the disease appears when the number of repeats varies from 40 to 50, and the juvenile form when it varies from 50 to 60. The higher the number of repeats, the earlier and more severe the disease. Paternal transmission associated with a high number of repeats results in earlier onset of the disease in subsequent generations (genetic anticipation). The pathophysiology is unknown, but results in progressive degeneration of certain neurons in the caudate nucleus and putamen, and sometimes other brain structures. This results is dysfunction of the GABAergic, glutaminergic and dopaminergic transmission pathways. Clinical diagnosis is based on the triad of motor, cognitive and psychiatric disorders.

It usually manifests itself in adulthood:

    In adults:

-        onset between 30 and 50 years of age

-        chorea, involuntary movements that progressively spread to all muscles, including the pharynx and respiratory muscles

-        progressive ataxia and cerebellar signs: falls

-        dystonia

-        behavioral problems and cognitive decline

-        bulbar disturbances with dysphagia and undernutrition (required gastrostomy)

-        loss of sleep

-        frequent suicide

In less than 10 % of cases, there is a juvenile form (generally inherited from the father) that begins between 5 and 12 years of age. Although often regarded as a standalone clinical entity, its seems that it is  a 'rigid' variant of the disease.

First signs:

-        behavioral and learning disorders (academic difficulties)

-        stiff gait, with a hypo - or bradykinesia, resembling Parkinson's disease

-        dysarthria, dysphagia (risk of death by inhalation pneumonia)

-        dysautonomic disorders: thermoregulation problems, hemodynamic instability, sleep disorders

-        scoliosis

-        late onset of choreic movements

-        seizures are more frequent (50%) than in the adult form (2%)

-        sometimes blepharospasm and abnormalities of eye movements

-        dementia and behavioral disorders get worse gradually.

     Treatment:

-        antipsychotics (D2-receptor blockers): olanzapine, risperidone

-        serotonin reuptake inhibitors: sertraline

-        deutetrabenazine: reduces the cerebral uptake of dopamine, serotonin, noradrenaline and histamine by inhibiting the MAO2 transporter.

There are other diseases that have the same clinical features as Huntington's disease, but are not caused by a mutation in the HTT gene.

These are phenocopies called HDL (for Huntington Disease Like).

A distinction is made between them:

-        HDL1 [MIM 603 210]: autosomal dominant transmission of a mutation of the PRNP gene (8q24.3).

-        HDL2 [MIM 606 438]: autosomal dominant transmission of a mutation of the JPH3 gene (16q24.2)

-        HDL3 [MIM 604 802]: autosomal recessive transmission of a gene mutation at 4p15.3

-        HDL4 [MIM 607 136]: or spinocerebellar ataxia type 17, autosomal dominant transmission of a TBP gene mutation (6q27)

-        McLeod syndrome: mutation of the XK gene (Xp21.1) (see this term)

-        neuroferritinopathy: FLL gene mutation (see this term)

-        chorea-acanthocytosis or neuroacanthocytosis: mutation of the VPS13A gene (9q21.2) (see this term)

Anesthetic implications:

behavioral disorders, convulsions; risk of inhalation pneumonia; interaction with symptomatic treatment: antipsychotics, antidepressants, benzodiazepines; do not interrupt usual treatment. Informed consent may be difficult to obtain. Avoid tramadol (risk of serotonin syndrome). Risk of arterial hypotension.

Risk of difficult intubation and poor swallowing during induction and on awakening. Avoid dopaminergic agents such as metoclopramide; previously reported increased sensitivity to pentothal and non-depolarizing curares has not been confirmed in the Mayo Clinic series. Systemic or epidural dexmedetomidine appears to reduce choreic movements. Body temperature monitoring.

In the case of spinal anesthesia, a change in the composition of cerebral proteins in the CSF could lead to a more extensive spinal block.

It is possible that patients with the disease have a higher frequency than the general population of a mutation of the Eu gene (allele Ef, see atypical anticholinesterases) responsible for resistance to fluorides; even in the homozygous form Ef - Ef, the extension of the duration of action of succinylcholine remains moderately prolonged, less than 1 hour usually.

References :

-        Gupta K, Leng CP.
Anaesthesia and juvenile Huntington’s disease.
Paediatr Anaesth 2000 ; 10 : 107-9.

-        Esen A, Karaaslan P, Akgun RC, Arslan G.
Successful spinal anesthesia in a patient with Huntington’s chorea.
Anesth Analg 2006; 103: 512-3.

-        Kivela JE, Sprung J, Southorn PA, Watson JC, Weingarten TN.
Anesthetic management of patients with Huntington disease.
Anesth Analg 2010; 110: 515-23

-        Kang J-M, Chung J-Y, Han JH, Kim Y-S, Lee BJ, Yi J-W.
Anesthetic management of a patient with Huntington’s chorea: a case report.
Korean J Anesthesiol 2013; 64: 262-4.

-        Nguyen PT, Meeks D, Liotiri D.
Anaesthesia and orphan disease : airway and anaesthetic management in Huntington’s disease.
BMJ Case Rep. 2017; bcr2017221354–bcr2017221354.

-        Soloniuk LJ, Jones J, Baker C, Bishawi M, Pasca I, Sinha A.
Neuraxial analgesia and anesthesia for labor and Cesarean delivery in a patient with Juvenile Huntington disease: a case report.
A&A Practice 2025;19:e01926

Updated: March 2025