Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.

SCA6 is typified by progressive and permanent cerebellar dysfunction. These cerebellar signs include ataxia and dysarthria, likely caused by cerebellar atrophy. Prior to diagnosis and the onset of major symptoms, patients often report a feeling of "wooziness" and momentary imbalance when turning corners or making rapid movements. The age at which symptoms first occur varies widely, from age 19 to 71, but is typically between 43 and 52. Other major signs of SCA6 are the loss of vibratory and proprioceptive sensation and nystagmus.

While most patients present with these severe progressive symptoms, others, sometimes within the same family, display episodic non-progressive symptoms more similar to episodic ataxia. Still others present with symptoms common to both SCA6 and familial hemiplegic migraine.

Individuals with KSS present initially in a similar way to those with typical CPEO. Onset is in the first and second decades of life.

The first symptom of this disease is a unilateral ptosis, or difficulty opening the eyelids, that gradually progresses to a bilateral ptosis. As the ptosis worsens, the individual commonly extends their neck, elevating their chin in an attempt to prevent the eyelids from occluding the visual axis. Along with the insidious development of ptosis, eye movements eventually become limited causing a person to rely more on turning the head side to side or up and down to view objects in the peripheral visual field.

Symptoms typically are onset in the adult years, although, childhood cases have also been observed. Common symptoms include a loss of coordination which is often seen in walking, and slurred speech. ADCA primarily affects the cerebellum, as well as, the spinal cord. Some signs and symptoms are:

BVVL is marked by a number of cranial nerve palsies, including those of the motor components involving the 7th and 9th-12th cranial nerves, spinal motor nerves, and upper motor neurons. Major features of BVVL include facial and neck weakness, fasciculation of the tongue, and neurological disorders from the cranial nerves. The neurological manifestations develop insidiously: they usually begin with sensorineural deafness, progress inexorably to paralysis, and often culminate in respiratory failure. Most mortality in patients has been from either respiratory infections or respiratory muscle paralysis. Pathological descriptions of BVVL include injury and depletion of 3rd-7th cranial nerves, loss of the spinal anterior horn cells, degeneration of Purkinje cells, as well as degeneration of the spinocerebellar and pyramidal tracts. The first symptoms in nearly all cases of BVVL is progressive vision loss and deafness, and the first initial symptoms are seen anywhere from one to three years.

Most cases of deafness are followed by a latent period that can extend anywhere from weeks to years, and this time is usually marked by cranial nerve degeneration. Neurological symptoms of BVVL include optic atrophy, cerebellar ataxia, retinitis pigmentosa, epilepsy and autonomic dysfunction. Non-neurological symptoms can include diabetes, auditory hallucinations, respiratory difficulties, color blindness, and hypertension.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

As characterized in Kearns' original publication in 1965 and in later publications, inconsistent features of KSS that may occur are weakness of facial, pharyngeal, trunk, and extremity muscles, hearing loss, small stature, electroencephalographic changes, cerebellar ataxia and elevated levels of cerebrospinal fluid protein.

The syndrome causes cerebellar ataxia (balance and coordination problems), mental retardation, congenital cataracts in early childhood, muscle weakness, inability to chew food, thin brittle fingernails, and sparse hair.

Small stature, mild to severe mental retardation and dysarthria (slow, imprecise speech) are usually present.

Various skeletal abnormalities (e.g., curvature of the spine) and hypergonadotropic hypogonadism often occur.

Muscle weakness is progressive, but life expectancy is near normal.

Individuals with this syndrome typically develop normally until reaching the second decade of their lives but the onset of symptoms has been observed as early as age seven. The first defect observed in individuals who suffer from this condition affects the auditory system and is known as bilateral nerve deafness. Another early symptom is the development of myopia (nearsightedness). In addition to bilateral nerve deafness and myopia, other symptoms that plague infected individuals early in disease progression include ataxia, muscle wasting, severe peripheral neuritic pain sometimes accompanied by elevated spinal fluid protein, and joint stiffness.

The central nervous system (CNS) is affected with deficits in the cerebral cortex which indicate signs of mental retardation even though psychological observations appear relatively normal for individuals studied. Atypical epilepsy is also a common feature of CNS malfunctioning including aphasia expressions, blurred vision, and numbness of the face and limbs.

In the third decade of the condition, individuals develop further visual problems including retinitis pigmentosa, and bilateral cataracts. Sufferers endure the restriction of visual fields, night blindness, and eventually severe or complete blindness.

Individuals with this syndrome exhibit many physical deformities including skeletal, epidermal, and subcutaneous abnormalities. The skeletal problems are characterized by scoliosis and muscle weakness indicative of the kyphoscoliotic type which follow muscle wasting and peripheral neuritis (nerve inflammation). Osteoporosis is also observed in many cases. Skin and subcutaneous atrophy is common as well as skin ulcerations due to inability of the skin to heal. One of the final manifestations of disease is baldness.There is no evidence that the progression of Flynn–Aird syndrome shortens the patient's life-span, but the terrible conditions certainly increase morbidity.

Autosomal dominant cerebellar ataxia (ADCA) is a form of spinocerebellar ataxia inherited in an autosomal dominant manner. ADCA is a genetically inherited condition that causes deterioration of the nervous system leading to disorder and a decrease or loss of function to regions of the body.

Degeneration occurs at the cellular level and in certain subtypes results in cellular death. Cellular death or dysfunction causes a break or faulty signal in the line of communication from the central nervous system to target muscles in the body. When there is impaired communication or a lack of communication entirely, the muscles in the body do not function correctly. Muscle control complications can be observed in multiple balance, speech, and motor or movement impairment symptoms. ADCA is divided into three types and further subdivided into subtypes known as SCAs (spinocerebellar ataxias).

The age of onset is in a child's infancy. Bilateral corneal opacification started in the second year of life and led to severe visual impairment. However, cornea surgery and replacement resulted in better vision.

Symptoms include a combination of spinocerebellar degeneration and corneal dystrophy. Mental retardation and slowly progressive cerebellar abnormalities were also diagnosed in patients. Other symptoms include corneal edema, thickening of Descemet membrane, and degenerative pannus. Abnormalities were found in muscle and sural nerves.

Spastic ataxia-corneal dystrophy syndrome (also known as Bedouin spastic ataxia syndrome) is an autosomally resessive disease. It has been found in an inbred Bedouin family. It was first described in 1986. A member of the family who was first diagnosed with this disease also had Bartter syndrome. It was concluded by its first descriptors Mousa-Al et al. that the disease is different from a disease known as corneal-cerebellar syndrome that had been found in 1985.

Symptoms include spastic ataxia, cataracts, macular corneal dystrophy and nonaxial myopia. Mental development is normal.

Brown-Vialetto-Van-Laere syndrome (BVVL), sometimes known as Brown's Syndrome, is a rare degenerative disorder often initially characterized by progressive sensorineural deafness.

The syndrome most often affects children, adolescents, and young adults. As knowledge of BVVL grows some adult patients have now been diagnosed. There is no known cure, however with prompt treatment the prognosis may be positive with some patients stabilizing and even minor improvements noted in certain cases.

Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA may occur in the 20s or 30s. Symptoms include any combination, but not necessarily all, of the following:

- Muscle weakness in the arms and legs

- Loss of coordination

- Vision impairment

- Hearing impairment

- Slurred speech

- Curvature of the spine (scoliosis)

- High plantar arches (pes cavus deformity of the foot)

- Diabetes (about 20% of people with Friedreich's ataxia develop carbohydrate intolerance and 10% develop diabetes mellitus)

- Heart disorders (e.g., atrial fibrillation, and resultant tachycardia (fast heart rate) and hypertrophic cardiomyopathy)

It presents before 22 years of age with progressive staggering or stumbling gait and frequent falling. Lower extremities are more severely involved. The symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. On average, after 10–15 years with the disease, patients are usually wheelchair bound and require assistance with all activities of daily living.

The following physical signs may be detected on physical examination:

- Cerebellar: nystagmus, fast saccadic eye movements, truncal ataxia, dysarthria, dysmetria.

- Lower motor neuron lesion: absent deep tendon reflexes.

- Pyramidal: extensor plantar responses, and distal weakness are commonly found.

- Dorsal column: Loss of vibratory and proprioceptive sensation occurs.

- Cardiac involvement occurs in 91% of patients, including cardiomegaly (up to dilated cardiomyopathy), symmetrical hypertrophy, heart murmurs, and conduction defects. Median age of death is 35 years, while females have better prognosis with a 20-year survival of 100% as compared to 63% in men.

20% of cases are found in association with diabetes mellitus.

Spinocerebellar ataxia type 6 (SCA6) is a rare, late-onset, autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, oculomotor disorders, peripheral neuropathy, and ataxia of the gait, stance, and limbs due to cerebellar dysfunction. Unlike other types, SCA 6 is not fatal. This cerebellar function is permanent and progressive, differentiating it from episodic ataxia type 2 (EA2) where said dysfunction is episodic. In some SCA6 families, some members show these classic signs of SCA6 while others show signs more similar to EA2, suggesting that there is some phenotypic overlap between the two disorders. SCA6 is caused by mutations in CACNA1A, a gene encoding a calcium channel α subunit. These mutations tend to be trinucleotide repeats of CAG, leading to the production of mutant proteins containing stretches of 20 or more consecutive glutamine residues; these proteins have an increased tendency to form intracellular agglomerations. Unlike many other polyglutamine expansion disorders expansion length is not a determining factor for the age that symptoms present.

Flynn–Aird syndrome is a rare, hereditary, neurological disease that is inherited in an autosomal dominant fashion. The syndrome involves defects in the nervous, auditory, skeletal, visual, and endocrine systems and encompasses numerous symptoms, bearing striking similarity to other known syndromes of neuroectodermal nature such as: Werner syndrome, Cockayne syndrome and Refsum syndrome.

The onset of Flynn–Aird syndrome typically occurs between ten and twenty years of age, however, the earliest case was diagnosed at age seven. As the syndrome progresses, initial symptoms tend to intensify and new symptoms become apparent. Unlike related syndromes and despite the intensity of symptoms in the disease progression, Flynn–Aird syndrome does not appear to shorten life expectancy.

The disease is characterized by early-onset dementia, ataxia, muscle wasting, skin atrophy, and eye abnormalities. In addition, patients have the potential of developing a number of other related symptoms such as: cataracts, retinitis pigmentosa, myopia (nearsightedness), dental caries, peripheral neuropathy (peripheral nerve damage), deafness, and cystic bone changes. This syndrome was first discovered in the early 1950s by American neurologists P. Flynn and Robert B. Aird who analyzed one family lineage inheritance pattern of this disease.

Not all of the DOOR symptoms are consistently present. They can vary in severity, and additional features can be noted in individuals affected by DOOR syndrome.

Some of these additional features are:

- Polyhydramnios (increased amniotic fluid during pregnancy) and increased nuchal fold during pregnancy

- Specific facial features such as a large nose

- Severe and sometimes refractory seizures, abnormalities on the magnetic resonance imaging of the brain

- Increased 2-oxoglutaric acid in the blood and urine - this compound is made or used by several enzymes

- Finger-like thumbs

- Visual impairment

- Peripheral neuropathy (nerves conducting sensation from extremities to the brain) and insensivity to pain

Intellectual impairment is present in all reported cases, but the severity can vary widely. The prognosis in terms of survival also varies greatly from early childhood till adulthood.

Autosomal recessive cerebellar ataxia type 1 (ARCA1) is a condition characterized by progressive problems with movement. Signs and symptoms of the disorder first appear in early to mid-adulthood. People with this condition initially experience impaired speech (dysarthria), problems with coordination and balance (ataxia), or both. They may also have difficulty with movements that involve judging distance or scale (dysmetria). Other features of ARCA1 include abnormal eye movements (nystagmus) and problems following the movements of objects with their eyes. The movement problems are slowly progressive, often resulting in the need for a cane, walker, or wheelchair.

Most cases of autosomal recessive cerebellar ataxia are early onset, usually around the age of 20. People with this type of ataxia share many characteristic symptoms including:

- frequent falls due to poor balance

- imprecise hand coordination

- postural or kinetic tremor of extremities or trunk

- dysarthria

- dysphasia

- vertigo

- diplopia

- lower extremity tendon reflexes

- dysmetria

- minor abnormalities in ocular saccades

- attention defects

- impaired verbal working memory and visuospatial skills

- Normal life expectancy

Autosomal recessive ataxias are generally associated with a loss of proprioception and vibration sense. Arreflexia is more common in autosomal recessive ataxia than autosomal dominant ataxias. Also, they tend to have more involvement outside of the nervous system. Mutations in subunit of the mitochondrial DNA polymerase (POLG) have been found to be a potential cause of autosomal recessive cerebellar ataxia.

The combination of muscular hypotonia and fixed dilated pupils in infancy is suspicious of Gillespie syndrome. Early onset partial aniridia, cerebellar ataxia, and mental retardation are hallmark of syndrome. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. The aniridia consisting of a superior coloboma and inferior iris hypoplasia, foveomacular dysplasia.

Atypical Gillespie syndrome associated with bilateral ptosis, exotropia, correctopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation.

Neurological signs ar nystagmus, mild craniofacial asymmetry, axial hypotonia, developmental delay, and mild mental retardation. Mariën P did not support the prevailing view of a global mental retardation as a cardinal feature of Gillespie syndrome but primarily reflect cerebellar induced neurobehavioral dysfunctions following disruption of the cerebrocerebellar anatomical circuitry that closely resembles the "cerebellar cognitive and affective syndrome" (CeCAS).

Congenital pulmonary stenosis and helix dysplasia can be associated.

SCA13 is typified by early onset, mildly progressive cerebellar ataxia with accompanying dysarthria, mental retardation, and nystagmus. Symptoms and age of onset can vary slightly according to the causative mutation.

An individual displaying MERRFs syndrome will manifest not only a single symptom, but regularly patients display more than one affected body part at a time. It has been observed that patients with MERRF syndrome will primarily display Myoclonus as a first symptom, along with it they can also manifest seizures, cerebellar ataxia and myopathy. Secondary features include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity or multiple lipomata. Additional symptoms include dementia, optic atrophy, bilateral deafness and peripheral neuropathy, spasticity, lipomatosis, and/or cardiomyopathy with wolff parkinson-white syndrome. Most patients will not exhibit all of these symptoms, however more than one of these symptoms will be present in a patient who has been diagnosed with MERRFS disease. Due to the multi-symptoms presented by the individual, the severity of the syndrome is very difficult to evaluate. Mitochondrial disorders may present at any age, and this holds truth for MERRS, since it forms part of them. Therefore, if a patient is presenting some of these symptoms, the doctor is able to narrow it down to MEERF mitochondrial disorder.

Diagnosis of MSS is based on clinical symptoms, magnetic resonance imaging (MRI) of the brain (cerebellar atrophy particularly involving the cerebellar vermis), and muscle biopsy.

It can be associated with mutations of the SIL1 gene, and a mutation can be found in about 50% of cases.

Differential diagnosis includes Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN), Marinesco–Sjögren like syndrome with chylomicronemia, carbohydrate deficient glycoprotein syndromes, Lowe syndrome, and mitochondrial disease.

Onset of symptoms usually occur in early adulthood and is characterized by intention tremor, progressive ataxia, convulsions, and myoclonic epileptic jerks.

Tremors usually affect one extremity, primarily the upper limb, and eventually involve the entire voluntary motor system. Overall, the lower extremity is usually disturbed less often than the upper extremity.

Additional features of the syndrome include: an unsteady gait, seizures, muscular hypotonia, reduced muscular coordination, asthenia, adiadochokinesia and errors with estimating range, direction, and force of voluntary movements. Mental deterioration can occur, however it is rare.

Non-progressive congenital ataxia (NPCA) is a non-progressive form of cerebellar ataxia which can occur with or without cerebellar hypoplasia.