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.

The initial description of AGS suggested that the disease was always severe, and was associated with unremitting neurological decline, resulting in death in childhood. As more cases have been identified, it has become apparent that this is not necessarily the case, with many patients now considered to demonstrate an apparently stable clinical picture, alive in their 4th decade. Moreover, rare individuals with pathogenic mutations in the AGS-related genes can be minimally affected (perhaps only with chilblains) and are in mainstream education, and even affected siblings within a family can show marked differences in severity.

In about ten percent of cases, AGS presents at or soon after birth (i.e. in the neonatal period). This presentation of the disease is characterized by microcephaly, neonatal seizures, poor feeding, jitteriness, cerebral calcifications (accumulation of calcium deposits in the brain), white matter abnormalities, and cerebral atrophy; thus indicating that the disease process became active before birth i.e. "in utero". These infants can have hepatosplenomegaly and thrombocytopaenia, very much like cases of transplacental viral infection. About one third of such early presenting cases, most frequently in association with mutations in "TREX1", die in early childhood.

Otherwise the majority of AGS cases present in early infancy, sometimes after an apparently normal period of development. During the first few months after birth, these children develop features of an encephalopathy with irritability, persistent crying, feeding difficulties, an intermittent fever (without obvious infection), and abnormal neurology with disturbed tone, dystonia, an exaggerated startle response, and sometimes seizures.

Glaucoma can be present at birth, or develop later. Many children retain apparently normal vision, although a significant number are cortically blind. Hearing is almost invariably normal. Over time, up to 40% of patients develop so-called chilblain lesions, most typically on the toes and fingers and occasionally also involving the ears. They are usually worse in the winter.

Aicardi–Goutières syndrome (AGS), which is completely distinct from the similarly named Aicardi syndrome, is a rare, usually early onset childhood, inflammatory disorder most typically affecting the brain and the skin (neurodevelopmental disorder). The majority of affected individuals experience significant intellectual and physical problems, although this is not always the case. The clinical features of AGS can mimic those of "in utero" acquired infection, and some characteristics of the condition also overlap with the autoimmune disease systemic lupus erythematosus (SLE). Following an original description of eight cases in 1984, the condition was first referred to as 'Aicardi–Goutières syndrome' (AGS) in 1992, and the first international meeting on AGS was held in Pavia, Italy, in 2001.

AGS can occur due to mutations in any one of a number of different genes, of which seven have been identified to date, namely: TREX1, RNASEH2A, RNASEH2B, RNASEH2C (which together encode the Ribonuclease H2 enzyme complex), SAMHD1, ADAR1, and IFIH1 (coding for MDA5). This neurological disease occurs in all populations worldwide, although it is almost certainly under-diagnosed. To date (2014) at least 400 cases of AGS are known.

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.

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.

Mohr–Tranebjærg syndrome (MTS) is a rare X-liked recessive syndrome also known as deafness–dystonia syndrome and caused by mutation in the TIMM8A gene. It was first described in 1960. The severity of the symptoms may vary, but they progress usually to severe deafness and dystonia and sometimes are accompanied by cortical deterioration of vision and mental deterioration.

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.

MRI: medial temporal lobe signal change bilateral hippocampal lesions, with signals that were hypointense in IR sequences and hyperintense in FLAIR.

Age: Children, Young Adult, Elderly

Sex: Both

Onset: Subacute

Clinical features NMDA Ab related patients in adult shows;

- Early features of higher cognitive dysfunction, confusion, behavioural changes, amnesia, dysphasia. Psychiatric: hallucinations, psychotic, agitation, depressive, anxiety, obsessive. Seizures: generalized, complex partial, simple partial.

- Late features: Spontaneous reduction in conscious level, Movement disorder: choreoathetoid (orofacial, upper limbs, lower limbs), parkinsonian, rigidity, myoclonus, oculogyric crises, opisthotonus, startle. Dysautonomia : tachy/brady-cardia, hyperhidrosis, persistent pyrexia, central hypoventilation, labile/high blood pressure, hypersalivation, pseudoobstruction, cardiac asystole.

NMDA Ab related patients in children and adolescent.

Commonly

- Behavioral or personality change, sometimes associated with

- Seizures and

- Sleep dysfunction;

- Severe speech deficits on admission

- Stereotyped movements,

- Autonomic instability

- Hypoventilation

Rarely

- Dyskinesias or dystonia;

Other Cases have similar presentation

- Disorientation,

- Hallucinations

- Confusion

- Memory loss

- Seizures: Partial temporal lobe. Pilomotor Status epilepticus

- Relative absence of cerebellar and brainstem sings

- Post partum psychosis

- Dyskinesias

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 present in the 3rd or 4th decade of life, but have been seen as early as the age of 14. It presents with torsion dystonia, particularly when presenting at a younger age, which then progresses to parkinsonism with or without ongoing dystonia. Often the two symptoms coexist.The parkinsonian features of x-linked dystonia parkinsonism include festinating gait, bradykinesia, blepharospasm, and postural instability. It often lacks a resting tremor, helping to differentiate it from Parkinson's disease.

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.

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.

Symptoms of cerebellar abiotrophy include ataxia or lack of balance, an awkward wide-legged stance, a head tremor (intention tremor) (in dogs, body tremors also occur), hyperreactivity, lack of menace reflex, stiff or high-stepping gait, coarse or jerky head bob when in motion (or in very young animals, when attempting to nurse), apparent lack of awareness of where the feet are (sometimes standing or trying to walk with a foot knuckled over), poor depth perception, and a general inability to determine space and distance. The symptoms, when taken as a group, are distinctive and not easily mimicked by other illnesses, though certain types of neurological injury and infection need to be ruled out. Verifying the diagnosis in a laboratory setting is possible only by examining the brain post-mortem to determine if there has been a loss of Purkinje cells.

Most affected animals have normal intelligence and mildly affected animals can, in theory, live out a normal lifespan. However, affected animals are quite accident-prone, and for this reason many animals that develop CA, particularly horses, are euthanized for humane reasons. Horses may experience difficulty stepping up and over objects, run into fences, fall easily, and even if allowed to mature to full growth, are generally considered unsafe to ride. Dogs may need lifetime assistance with tasks such as climbing stairs.

In horses, the symptoms may worsen from the time of onset for six to 12 months, but if not severe enough to mandate euthansia, they stabilize over time. In some dog breeds, symptoms appear to progressively worsen, but research is not consistent on this point. There also is some evidence that affected animals partially compensate for the condition by cognitively learning alternative methods for moving or to determine distance, and thus appear to improve because they become less accident-prone.

Segawa Syndrome (SS) also known as Dopamine-responsive dystonia (DRD), Segawa's disease, Segawa's dystonia and hereditary progressive dystonia with diurnal fluctuation, is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years (variable start age).

Characteristic symptoms are increased muscle tone (dystonia, such as clubfoot) and Parkinsonian features, typically absent in the morning or after rest but worsening during the day and with exertion. Children with SS are often misdiagnosed as having cerebral palsy. The disorder responds well to treatment with levodopa.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

X-linked dystonia parkinsonism (XDP), also known as Lubag Syndrome or X-linked Dystonia of Panay, is a rare x-linked progressive movement disorder with high penetrance found almost exclusively in males from the Panay, Philippines. It is characterized by dystonic movements first typically occurring in the 3rd and 4th decade of life. The dystonic movements often either coexist or develop into parkinsonism within 10 years of disease onset.

Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait.

About half of affected patients develop cherry-red spots in the eye.

Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia.

- Autosomal recessive disorder; beta-galactosidase deficiency; neuronal storage of GM1 ganglioside and visceral storage of galactosyl oligosaccharides and keratan sulfate.

- Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis.

- Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some

- Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia

- Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure

- Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. *Dysostosis multiplex (as in the mucopolysaccharidoses)

- 10–80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10-fold elevated (20–50-fold increased in viscera)

- Galactose-containing oligosacchariduria and moderate keratan sulfaturia

- Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4).

Harding ataxia, also known as Early onset cerebellar ataxia with retained reflexes (EOCARR), is an autosomal recessive cerebellar ataxia originally described by Harding in 1981. This form of cerebellar ataxia is similar to Friedreich ataxia including that it results in poor reflexes and balance, but differs in several ways, including the absence of diabetes mellitus, optic atrophy, cardiomyopathy, skeletal abnormalities, and the fact that tendon reflexes in the arms and knees remain intact. This form of ataxia is characterized by onset in the first 20 years, and is less severe than Friedreich ataxia. Additional cases were diagnosed in 1989, 1990, 1991, and 1998.

The disease typically starts in one limb, typically one leg. Progressive dystonia results in clubfoot and tiptoe walking. The symptoms can spread to all four limbs around age 18, after which progression slows and eventually symptoms reach a plateau. There can be regression in developmental milestones (both motor and mental skills) and failure to thrive in the absence of treatment.

In addition, SS is typically characterized by signs of parkinsonism that may be relatively subtle. Such signs may include slowness of movement (bradykinesia), tremors, stiffness and resistance to movement (rigidity), balance difficulties, and postural instability. Approximately 25 percent also have abnormally exaggerated reflex responses (hyperreflexia), particularly in the legs. These symptoms can result in a presentation that is similar in appearance to that of Parkinson's Disease.

Many patients experience improvement with sleep, are relatively free of symptoms in the morning, and develop increasingly severe symptoms as the day progresses (i.e., diurnal fluctuation). Accordingly, this disorder has sometimes been referred to as "progressive hereditary dystonia with diurnal fluctuations." Yet some SS patients do not experience such diurnal fluctuations, causing many researchers to prefer other disease terms.

- Other symptoms - footwear

- excessive wear at toes, but little wear on heels, thus replacement of shoes every college term/semester.

- Other symptoms - handwriting

- near normal handwriting at infants/kindergarten (ages 3–5 school) years.

- poor handwriting at pre-teens (ages 8–11 school) years.

- very poor (worse) handwriting during teen (qv GCSE/A level-public exams) years.

- bad handwriting (worsening) during post-teen (qv university exams) years.

- very bad handwriting (still worsening) during adult (qv post-graduate exams) years.

- worsening pattern of sloppy handwriting best observed by school teachers via termly reports.

- child sufferer displays unhappy childhood facial expressions (depression.?)

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:

Most symptoms of people with post-viral cerebellar ataxia deal to a large extent with the movement of the body. Some common symptoms that are seen are clumsy body movements and eye movements, difficulty walking, nausea, vomiting, and headaches.

Onset of late infantile GM1 is typically between ages 1 and 3 years.

Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

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.