Here is a description of a few forms of dominant autosomic ataxias, in other words the gene of one single parent is necessary in order to transmit the disease. These dominant ataxias are classified by type-I-II-III representing the age of appearance, the severity and the variety of the symptoms. The same thing for spinocerebellar ataxia which is categorized by around twenty types called SCA1 – SCA30…
Type I : one finds other neurological troubles without affecting the eye (5 genes are involved)
Type II : one finds other neurological signs with an affliction of the retina of the eye (relatively rare)
Type III : only the cerebellum is affected.
Mode of transmission : autosomic (afflicts both sexes) and dominant ( one single parent can transmit the disease).
Age : affects the adult at a mature age (around 40 years) but precocious forms can affect children and later forms can affect seniors. The age is variable even within the same family. The disease leads to a wheelchair.
Evolution : the evolutive rhythm is often slowly progressive and extremely variable leading to a loss of autonomy.
Cause : many different genes. At least 14 of which several are known. The known mutations consist of a repeated expansion of trinucleotides of which the unstable character is at the origin of the phenomenon of anticipation since its appearance at an earlier age is observed.
Symptoms : cerebellar ataxia, problem of balance, of coordination and of elocution, sensorial losses, muscular weakness, difficulty swallowing and nystagmus.
Definition : Affliction of the cerebellum which brings about troubles of balance and of the coordination of movements. Affliction characterized by the association of lesions on the level of the cerebellar trunk and the cerebellum and especially the white substance of the cerebellum, the cerebellar peduncle and the bulbous olives. Otherwise stated, OPCA is the progressive destruction of the nervous cells which link several different structures of the encephalon part of the central nervous system. These degenerations go right to the cerebellum. They are at the origin of the cerebellar syndrome, that is to say, the clinical signs which the afflicted person presents.
Cause : several genes. The expansion of trinucleotides is easily tested and confirms the diagnosis in a person belonging to a family which already has cases or even in an isolated case.
Age : variable including in the same family. In general, around 40 years of age (always at an adult age).
Evolution : slowly progressive. Variable from one individual to another. It is sometimes complicated by troubles afflicting the sphincters which are the muscles allowing the closing and the opening of orifices. Some patients present a muscular hypertrophy characterized by a contraction of the muscles.
Frequency : the risk is one child out of two of an afflicted subject.
Symptoms : A cerebellar syndrome characterized thusly :
- excessive muscular slackening (excessive muscular hypotonia)
- an unsure walk (resembles a case of intoxication) and when he is standing he has a tendency to spread his legs to increase his balance.
- an impossibility or difficulty to execute in totality the movements ordered in the brain.
- the gestures go too far (hypermetria). The movements begin somewhat late and most often overreach the goal which the person had intended. The direction is nevertheless kept and there is sometimes trembling. Changing movements is no longer possible.
Cause : genetic (a repeated expansion of glutamate).
Mode of transmission : dominant autosomic (afflicts both sexes and one single parent is sufficient in order to transmit the disease and afflict 50% of the children.
Origins : Portuguese, French, Chinese, Japanese, German, American (more frequent in the Portuguese and the Japanese).
Gene : the gene is discovered. SCA3 is due to an expanded CAG repeat in a coding region of the SCA3 gene, encoding ataxin-3, a protein thought to be involved in processing of other proteins. Ataxin-3 is also called MJD protein 1. Like the other dominant polyglutamine diseases, the toxic effect is believed to be primarily due to a gain of function of the mutated protein, rather than a lost function of the wild-type.
Appearance : the disease appears between 30 and 40 years of age and leads to a wheelchair. About 25% of dominant ataxias are SCA3 type.
Symptoms : cerebellar ataxia, ocular paralysis, difficulty swallowing, nystagmus.
Treatment of manifestations: Acetazolamide (ACTZ), a carbonic-anhydrase (CA) inhibitor, may reduce the frequency and severity of the attacks in some but not all affected individuals. Antiepileptic drugs (AEDs) may significantly reduce the frequency of the attacks in some individuals.
Prevention of secondary complications: Joint contractures can be prevented by appropriate physiotherapy.
Surveillance: annual neurologic examination.
Agents/circumstances to avoid: General anesthetics have occasionally been reported to precipitate or aggravate neuromyotonia.
Genetic counseling. EA1 is inherited in an autosomal dominant manner. Most individuals diagnosed with EA1have an affected parent; to date, only one de novo mutation has been reported. Each child of an individual with EA1 has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation has been identified in an affected family member.
Source: Mauro Pessia, Michael G Hanna. Episodic Ataxia Type 1. GeneReviews [Internet].
Diagnosis/testing. The diagnosis of EA2 is most commonly made on clinical grounds. MRI can demonstrate atrophy of the cerebellar vermis. Mutations in CACNA1A can cause EA2. Molecular genetic testing is available on a clinical basis for CACNA1A.
Treatment of manifestations: Acetazolamide is effective in controlling or reducing the frequency and severity of attacks; although generally well tolerated, the most common side effects are paresthesias of the extremities, rash, and renal calculi; acetazolamide does not appear to prevent the progression of interictal symptoms.
Surveillance: Annual neurologic examination.
Agents/circumstances to avoid: Phenytoin has been reported to exacerbate symptoms.
Genetic counseling. EA2 is inherited in an autosomal dominant manner. Most individuals with a diagnosis of EA2 have an affected parent. The proportion of cases caused by de novo gene mutations is unknown. Offspring of affected individuals have a 50% chance of inheriting the disease-causing gene mutation. Prenatal testing is available for pregnancies at increased risk for EA2 if the mutation has been identified in the family.
Source: Sian Spacey. Episodic Ataxia Type 2. GeneReviews [Internet].