Chorea

CHOREA

Choreiform movements are brief, irregular, random quasi-purposeful-appearing movements that flow from one body part to another.
Huntington's disease affects ~ 1/10,000 in the Western World
Sydenham's which is the most common cause of acute onset chorea in childhood
There are numerous other causes of chorea beyond our scope, here.

Huntington's disease

Clinical Correlation: Huntington's disease

Genetics

Huntington's disease is secondary to a mutation on the short arm of chromosome 4, in the HTT (aka IT15) gene: a CAG trinucleotide repeat, which encodes for the huntingtin protein. It encodes a polyglutamine ('polyQ') stretch at the N-terminus of the huntingtin protein.
HD is an autosomal dominant disorder with significant genetic anticipation: the sequence length is unstable and can expand during meiosis, especially down paternal inheritance lines.
The anticipation helps us remember that this is a trinucleotide repeat disorder, specifically a CAG repeat disorder:

Huntington's disease (CAG), myotonic dystrophy (CTG), and fragile X syndrome CGG) are the three classic trinucleotide repeat expansion disorders: the trinucleotide sequence is repeated many times in a row.
Additional CAG repeat disorders include: Kennedy's disease (aka X-linked spinal and bulbar muscular atrophy), spinocerebellar ataxia type 1 (SCA 1) and type 3 (SCA3, aka Machado-Joseph disease).

Pathology ("CAG" mneomnic)

CAG highlights some key aspects of HD neuropathology:
On gross examination, there is caudate (C) and putamen (aka striatum) atrophy (A) with resultant anterior horn dilatation.
Accordingly, there is a loss of striatal GABAergic (G) medium spiny neurons, which is what primarily constitutes the striatum.

Mneomnic via Number 4

As a menomnic, use the number "4" to remember some core features of HD:

The HD gene is on chromosome 4
Greater than 40 CAG repeats is abnormal (but, truly, anything more than 36 can be symptomatic)
The average age of onset is 40 years-old but the longer the repeat length, the earlier the age of onset.

Onset younger than 20 years old, is referred to as Juvenile HD; it manifests with an akinetic-rigid syndrome, rather than chorea, referred to as the Westphal variant, which is typically the end-stage of HD in adults.

Clinical

HD is predominantly a neuropsychiatric and movement disorder.
It's often mistaken as alcoholism early on but ultimately becomes parkinsonian, later. As well, typical survival from onset is 15 years, much like the timeline of degeneration in Parkinson's disease.

Clinical Progression

Clinical progression involves the following key domains.

Psychiatric. Depression and anxiety, early, and obsessive/compulsive thoughts, profound apathy, and physical aggression, later. Note that suicide is the 2nd most common cause of death in HD.
Cognitive. Executive dysfunction, early, such as trouble with organizational tasks, planning, and task sequencing.
Simple abnormal involuntary movements: tics, dystonia, myoclonus.
Complex abnormal involuntary movements: Chorea (excessive movements that flow from body part to body part).
Failure of voluntary movements: Akinetic, rigid syndrome (parkinsonism).

Sydenham's chorea

Clinical Correlation: Sydenham's chorea

The chorea is of the entire body, including the face and tongue (called serpent tongue).

It arises anywhere from weeks to months (7 to 180 days) following group A beta-hemolytic streptococcal infection (typically manifesting with pharyngitis).
The pathology involves an autoimmune attack of the basal ganglia, most likely.
The symptoms resolve within weeks to months (21 – 180 days) but can return in adulthood, especially during the 1st trimester of pregnancy (called: chorea gravidarum).

Additional Clinical Features of Sydenhams' Chorea

Additional manifestations include motor impairment (eg, incoordination, gait abnormality, impairment of activities of daily living), flaccid muscle weakness, and psychological and behavioral issues (eg, anxiety, depression, obsessive compulsive behaviors (along with tics)) accompany the chorea.
High blood titers of streptococcal antibodies (ASO and antiDNAseB) and rheumatic heart disease (see below) can support the diagnosis.
Treatment typically involves: chorea suppressing medication (eg, haloperidol or tetrabenazine); antibiotic therapy to prevent rheumatic heart disease; short-term immune therapy.

Sydenham's Chorea & Rheumatic Fever