Classification systems for malformations of the cerebellum are varied and are constantly being revised as greater understanding of the underlying genetics and embryology of the disorders is uncovered. A classification proposed by Patel S in 2002 divides cerebellar malformations in two broad groups; those with cerebellar hypoplasia and; those with cerebellar dysplasia.

- I. Cerebellar hypoplasia

- A. Focal hypoplasia

- 1. Isolated vermis

- 2. One hemisphere hypoplasia

- B. Generalized hypoplasia

- 1. With enlarged fourth ventricle (“cyst,”), Dandy-Walker continuum

- 2. Normal fourth ventricle (no “cyst”)

- a. With normal pons

- b. With small pons i. Normal foliation

- a) Pontocerebellar hypoplasias of Barth, types I and II

- b) Cerebellar hypoplasias, not otherwise specified

Non-progressive early onset ataxia and poor motor learning are the commonest presentation.

The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. An increase in the size of the fluid spaces surrounding the brain as well as an increase in pressure may also be present. The syndrome can appear dramatically or develop unnoticed.

Symptoms, which often occur in early infancy, include slower motor development and progressive enlargement of the skull. In older children, symptoms of increased intracranial pressure such as irritability, vomiting, and convulsions and signs of cerebellar dysfunction such as unsteadiness and lack of muscle coordination or jerky movements of the eyes may occur. Other symptoms include increased head circumference, bulging at the back of the skull, problems with the nerves that control the eyes, face and neck, and abnormal breathing patterns.

Dandy–Walker syndrome is frequently associated with disorders of other areas of the central nervous system including absence of the corpus callosum, the bundle of axons connecting the two cerebral hemispheres, and malformations of the heart, face, limbs, fingers and toes.

The Dandy–Walker complex is a genetically sporadic disorder that occurs one in every 30,000 live births. Prenatal diagnosis and prognosis of outcomes associated with Dandy–Walker can be difficult. Prenatal diagnosis is possible with ultrasound. Because the syndrome is associated with an increased risk for fetal karyotype abnormalities, amniocentesis can be offered after prenatal diagnosis. There is a relative contraindication of taking Warfarin during pregnancy, as it is associated with an increased risk of Dandy–Walker syndrome if taken during the first trimester.

Microlissencephaly Type B or Barth microlissencephaly syndrome: is a microlissencephaly with thick cortex, severe cerebellar and brainstem hypoplasia. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes.

This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), severe congenital microcephaly, weak respiratory effort, and survival for only a few hours or days. Barth described two siblings with this type as having a very low brainweight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.

The DWS malformation is the most severe presentation of the syndrome. The posterior fossa is enlarged and the tentorium is in high position. There is complete agenesis of the cerebellar vermis. There is also cystic dilation of the fourth ventricle, which fills the posterior fossa. This often involves hydrocephalus and complications due to associated genetic conditions, such as Spina Bifida.

Microlissencephaly Type A or Norman-Roberts syndrome (NRS): a microlissencephaly with thick cortex without infratentorial anomalies.

Other clinical features may include: a bitemporal narrowing, a broad nasal root. There is postnatal growth retardation, severe mental retardation associated with pyramidal spasticity and epilepsy. This entity could be identical to "lissencephaly with cerebellar hypoplasia type B" (LCHb), and therefore linked to mutations in "RELN" gene.

There are various symptoms of colpocephaly and patients can experience effects ranging from mild to severe. Some patients do not show most of the symptoms related to colpocephaly, such as psychomotor abnormalilities and agenesis of the corpus callosum. In some cases, signs appear later on in life and a significant number of children suffer only from minor disabilities.

The following list includes common symptoms of colpocephaly.

- partial or complete agenesis of the corpus callosum

- intellectual disability

- motor abnormalities

- visual defects such as, crossing of the eyes, missing visual fields, and optic nerve hypoplasia

- spasticity

- seizures

- cerebral palsy

Intracranial abnormalities include:

- Microcephaly

- Agenesis of the corpus callosum

- Meningomyelocele

- Lissencephaly

- Periventricular leukomalacia (PVL)

- Enlargement of the cisterna magna

- Cerebellar hypoplasia

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.

Cerebellar agenesis is a rare condition in which a brain develops without the cerebellum. The cerebellum controls smooth movement, and when it does not develop, the rest of the brain must compensate, which it cannot do completely. The condition is not fatal on its own, but people born without a cerebellum experience severe developmental delays, language deficits, and neurological abnormalities. As children with cerebellar agenesis get older, their movements usually improve. It can co-exist with other severe malformations of the central nervous system, like anencephaly, holoprosencephaly, and microencephaly.

The condition was first reported in 1831. 10 cases had been reported as of 1998. Agenesis of one half or another part of the cerebellum is more common than complete agenesis.

Cerebellar agenesis can be caused by mutations in the PTF1A gene.

Usually symptoms of cerebellar hypoplasia can be seen immediately at birth in cats, but sometimes can take two months or so to become apparent in dogs. Cerebellar hypoplasia causes jerky movements, tremors and generally uncoordinated motion. The animal often falls down and has trouble walking. Tremors increase when the animal is excited and subside when at ease.

Various degrees of intensity and locations of epilepsy are associated with malformations of cortical development. Researchers suggest that approximately 40% of children diagnosed with drug-resistant epilepsy have some degree of cortical malformation.

Lissencephaly (to which pachygyria is most closely linked) is associated with severe mental retardation, epilepsy, and motor disability. Two characteristics of lissencephaly include its absence of convolutions (agyria) and decreased presence of convolutions (pachygyria). The types of seizures associated with lissencephaly include:

- persisting spasms

- focal seizures

- tonic seizures

- atypical seizures

- atonic seizures

Other possible symptoms of lissencephaly include telecanthus, estropia, hypertelorism, varying levels of mental retardation, cerebellar hypoplasia, corpus callosum aplasia, and decreased muscle tone and tendon reflexes. Over 90% of children affected with lissencephaly have seizures.

Patients with subcortical band heterotopia (another disorder associated with pachygyria) typically have milder symptoms and their cognitive function is closely linked to the thickness of the subcortical band and the degree of pachygyria present.

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

The classical triad of symptoms that defines 3C syndrome includes certain heart defects, hypoplasia (underdevelopment) of the cerebellum, and cranial dysmorphisms, which can take various forms. The heart defects and cranial dysmorphisms are heterogeneous in individuals who are all classed as having Ritscher-Schinzel syndrome.

Heart defects commonly seen with Ritscher-Schinzel syndrome are associated with the endocardial cushion and are the most important factor in determining a diagnosis. The mitral valve and tricuspid valve of the heart can be malformed, the atrioventricular canal can be complete instead of developing into the interatrial septum and interventricular septum, and conotruncal heart defects, which include tetralogy of Fallot, double outlet right ventricle, transposition of the great vessels, and hypoplastic left heart syndrome. Aortic stenosis and pulmonary stenosis have also been associated with 3C syndrome.

The cranial dysmorphisms associated with 3C syndrome are heterogeneous and include a degree of macrocephaly, a large anterior fontanel, a particularly prominent occiput and forehead, ocular hypertelorism (wide-set eyes), slanted palpebral fissures, cleft palate, a depressed nasal bridge, cleft palate with associated bifid uvula, low-set ears, micrognathia (an abnormally small jaw), brachycephaly (flattened head), and ocular coloboma. Low-set ears are the most common cranial dysmorphism seen in 3C syndrome, and ocular coloboma is the least common of the non-concurrent symptoms (cleft lip co-occurring with cleft palate is the least common).

Cranial dysplasias associated with 3C syndrome are also reflected in the brain. Besides the cerebellar hypoplasia, cysts are commonly found in the posterior cranial fossa, the ventricles and the cisterna magna are dilated/enlarged, and Dandy-Walker malformation is present. These are reflected in the developmental delays typical of the disease. 75% of children with 3C syndrome have Dandy-Walker malformation and hydrocephalus.

Signs and symptoms in other body systems are also associated with 3C syndrome. In the skeletal system, ribs may be absent, and hemivertebrae, syndactyly (fusion of fingers together), and clinodactyly (curvature of the fifth finger) may be present. In the GI and genitourinary systems, anal atresia, hypospadia (misplaced urethra), and hydronephrosis may exist. Adrenal hypoplasia and growth hormone deficiency are associated endocrine consequences of Ritscher-Schinzel syndrome. Some immunodeficiency has also been reported in connection with 3C syndrome.

Many children with the disorder die as infants due to severe congenital heart disease. The proband of Ritscher and Schinzel's original study was still alive at the age of 21.

A fetus with 3C syndrome may have an umbilical cord with one umbilical artery instead of two.

Colpocephaly is characterized by disproportionately large occipital horns of the lateral ventricles (also frontal and temporal ventricles in some cases). MRI and CT scans of patients demonstrate abnormally thick gray matter with thin poorly myelinated white matter. This happens as a result of partial or complete absence of the corpus callosum. Corpus callosum is the band of white matter connecting the two cerebral hemispheres. The corpus callosum plays an extremely important role in interhemispheric communication, thus lack of or absence of these neural fibers results in a number of disabilities.

The lemon sign on CT scans of patients refers to the shape of the fetal skull when the frontal bones lose their normal convex contour and appear flattened or inwardly scalloped. This gives the skull a shape similar to that of a lemon. The sign is seen on transverse sonograms of the fetal cranium obtained at the level of the ventricles.

A special case is found in literature where lissencephaly, colpocephaly, and septal agenesis are all present together. The CT scans of the patient shows the ventricular system having a unique appearance of a crown of a king. This is referred to as the 'CROWN SIGN'.

Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency. is a rare genetic disorder. The disorder is characterized by partial aniridia (meaning that part of the iris is missing), ataxia (motor and coordination problems), and, in most cases, intellectual disability. It is heterogeneous, inherited in either an autosomal dominant or autosomal recessive manner. Gillespie syndrome was first described by American ophthalmologist Fredrick Gillespie in 1965.

There are several bacterial infections and viral infections such as feline panleukopenia, caused by feline parvovirus (while in utero), that can result in the disorder in both cats and dogs. The disease can also be caused by malnutrition, poisoning, injury or general accidents during development in the fetus.

Neuroimaging like MRI is important. However, there was considerable intrafamilial variability regarding neuroimaging, with some individuals showing normal MRI findings. Early individual prognosis of such autosomal recessive cerebellar ataxias is not possible from early developmental milestones, neurological signs, or neuroimaging.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by progressive atrophy of various parts of the brain such as the cerebellum or brainstem (particularly the pons). Where known, these disorders are inherited in an autosomal recessive fashion. There is no known cure for PCH.

The blockage of cerebrospinal fluid (CSF) flow may also cause a syrinx to form, eventually leading to syringomyelia. Central cord symptoms such as hand weakness, dissociated sensory loss, and, in severe cases, paralysis may occur.

Microcephalic osteodysplastic primordial dwarfism (MOPD) type II is an autosomal multisystem disorder including severe pre- and post-natal growth retardation, microcephaly with Seckel syndrome-like facial appearance, and distinctive skeletal alterations. Usually those affected have mild to moderate mental retardation. This female child is the first born of nonconsanguineous parents at 35 weeks gestation through a cesarean section due to intrauterine growth retardation. She had a retarded psychomotor development and was repeatedly hospitalized during her first six months of life due to recurring respiratory infections. Her electroencephalography, auditory brainstem response evaluation, and chromosomal analysis were relatively normal. A brain MRI revealed thickened cerebral cortices with few and large gyri prominently in the frontal and posterior temporal regions, incomplete development of the Sylvian fissures, and dilatation of the posterior horns of the lateral ventricles (colpocephaly). Usually only mild brain malformations are associated with MOPD type II. The imaging findings of this child’s brain most likely represent diffuse pachygyria, a mild form of lissencephaly. This child’s neurodevelopmental findings were mild when compared to previous reports of a well-defined chromosome 17-linked and X-linked lissencephaly in a bedridden patient with severe developmental delays.

3C syndrome, also known as CCC dysplasia, Craniocerebellocardiac dysplasia or Ritscher–Schinzel syndrome, is a rare condition, whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.

There are different signs and symptoms for different forms of pontocerebellar hypoplasia, at least six of which have been described by researchers. All forms involve abnormal development of the brain, leading to slow development, movement problems, and intellectual impairment.

The following values seem to be aberrant in children with CASK gene defects: lactate, pyruvate, 2-ketoglutaric acid, adipic acid, and suberic acid which seems to support the thesis that CASK affects mitochondrial function.

Thymic hypoplasia is a condition where the thymus is underdeveloped or involuted.

Calcium levels can be used to distinguish between the following two conditions associated with thymic hypoplasia:

- 22q11.2 deletion syndrome: hypocalcemia

- Ataxia telangiectasia: normal levels of calcium

Syringomyelia is a chronic progressive degenerative disorder characterized by a fluid-filled cyst located in the spinal cord. Its symptoms include pain, weakness, numbness, and stiffness in the back, shoulders, arms or legs. Other symptoms include headaches, the inability to feel changes in the temperature, sweating, sexual dysfunction, and loss of bowel and bladder control. It is usually seen in the cervical region but can extend into the medulla oblongata and pons or it can reach downward into the thoracic or lumbar segments. Syringomyelia is often associated with Chiari malformation type I and is commonly seen between the C-4 and C-6 levels. The exact development of syringomyelia is unknown but many theories suggest that the herniated tonsils in Chiari malformation type I form a "plug" which does not allow an outlet of CSF from the brain to the spinal canal. Syringomyelia is present in 25% of patients with Chiari malformation.

Usually associated with diaphragmatic hernia,

pulmonary hypoplasia,

imperforate anus,

micropenis,

bilateral cryptorchidism,

cerebral ventricular dilation,

camptodactyly,

agenesis of sacrum,

low-set ear.

- Fryns et al. (1979) reported 2 stillborn sisters with a multiple congenital anomaly syndrome characterized by coarse facies with cloudy corneae, diaphragmatic defects, absence of lung lobulation, and distal limb deformities. A sporadic case was reported by Goddeeris et al. (1980). Fitch (1988) claimed that she and her colleagues were the first to describe this disorder. In 1978 they reported a single infant, born of second-cousin parents, who had absent left hemidiaphragm, hydrocephalus, arhinencephaly, and cardiovascular anomalies.

- Lubinsky et al. (1983) reported a brother and sister with Fryns syndrome who both died in the neonatal period. Facial anomalies included broad nasal bridge, microretrognathia, abnormal helices, and cleft palate. Other features included distal digital hypoplasia, lung hypoplasia, and urogenital abnormalities, including shawl scrotum, uterus bicornis, and renal cysts. They were discordant for diaphragmatic hernia, cleft lip, and Dandy–Walker anomaly.

- Meinecke and Fryns (1985) reported an affected child; consanguinity of the parents supported recessive inheritance. They noted that a diaphragmatic defect had been described in 4 of the 5 reported cases and lung hypoplasia in all. Young et al. (1986) reported a sixth case. The male infant survived for 12 days. These authors listed corneal clouding, camptodactyly with hypoplastic nails, and abnormalities of the diaphragm as cardinal features.

- Samueloff et al. (1987) described a family in which all 4 children had Fryns syndrome and neonatal mortality. Features included hypoplastic lungs, cleft palate, retrognathia, micrognathism, small thorax, diaphragmatic hernia, distal limb hypoplasia, and early onset of polyhydramnios with premature delivery. Schwyzer et al. (1987) described an affected infant whose parents were second cousins.

- Moerman et al. (1988) described infant brother and sister with the syndrome of diaphragmatic hernia, abnormal face, and distal limb anomalies. Both died shortly after birth with severe respiratory distress. Ultrasonography demonstrated fetal hydrops, diaphragmatic hernia, and striking dilatation of the cerebral ventricles in both infants. Post-mortem examination showed Dandy–Walker malformation, ventricular septal defect, and renal cystic dysplasia.

- Cunniff et al. (1990) described affected brothers and 3 other cases, bringing the total reported cases of Fryns syndrome to 25. One of the affected brothers was still alive at the age of 24 months. Bilateral diaphragmatic hernias had been repaired on the first day of life. He required extracorporeal membrane oxygenation therapy for 5 days and oscillatory therapy for 3 months. Ventriculoperitoneal shunt was required because of slowly progressive hydrocephalus. Scoliosis was associated with extranumerary vertebral bodies and 13 ribs. Because of delayed gastric emptying, a gastrostomy tube was inserted. In addition, because of persistent chylothorax, he underwent decortication of the right lung and oversewing of the thoracic duct.

- Kershisnik et al. (1991) suggested that osteochondrodysplasia is a feature of Fryns syndrome.

- Willems et al. (1991) suggested that a diaphragmatic hernia is not a necessary feature of Fryns syndrome. They described a child with all the usual features except for diaphragmatic hernia; the diaphragm was reduced to a fibrous web with little muscular component. Bartsch et al. (1995) presented 2 unrelated cases with a typical picture of Fryns syndrome but without diaphragmatic hernia. One of these patients was alive at the age of 14 months, but was severely retarded. Bamforth et al. (1987) and Hanssen et al. (1992) also described patients with this syndrome who survived the neonatal period. In the report of Hanssen et al. (1992), 2 older sibs had died in utero. The reports suggested that survival beyond the neonatal period is possible when the diaphragmatic defect and lung hypoplasia are not present. However, mental retardation has been present in all surviving patients.

- Vargas et al. (2000) reported a pair of monozygotic twins with Fryns syndrome discordant for severity of diaphragmatic defect. Both twins had macrocephaly, coarse facial appearance, hypoplasia of distal phalanges, and an extra pair of ribs. Twin A lacked an apparent diaphragmatic defect, and at 1 year of age had mild developmental delay. Twin B had a left congenital diaphragmatic hernia and died neonatally. The authors suggested that absence of diaphragmatic defect in Fryns syndrome may represent a subpopulation of more mildly affected patients.

- Aymé, "et al." (1989) described 8 cases of Fryns syndrome in France. The most frequent anomalies were diaphragmatic defects, lung hypoplasia, cleft lip and palate, cardiac defects, including septal defects and aortic arch anomalies, renal cysts, urinary tract malformations, and distal limb hypoplasia. Most patients also had hypoplastic external genitalia and anomalies of internal genitalia, including bifid or hypoplastic uterus or immature testes. The digestive tract was also often abnormal; duodenal atresia, pyloric hyperplasia, malrotation and common mesentery were present in about half of the patients. When the brain was examined, more than half were found to have Dandy–Walker anomaly and/or agenesis of the corpus callosum. A few patients demonstrated cloudy cornea. Histologically, 2 of 3 patients showed retinal dysplasia with rosettes and gliosis of the retina, thickness of the posterior capsule of the lens, and irregularities of Bowman membrane.

- Alessandri et al. (2005) reported a newborn from the Comores Islands with clinical features of Fryns syndrome without diaphragmatic hernia. They noted that diaphragmatic hernia is found in more than 80% of cases and that at least 13 other cases had been reported with an intact diaphragm.

- In a postneonatal survivor of Fryns syndrome, Riela et al. (1995) described myoclonus appearing shortly after birth, which was well controlled on valproate. Progressive cerebral and brainstem atrophy was noted on serial MRIs made at 3 months and after 6 months of age.

- Van Hove et al. (1995) described a boy with Fryns syndrome who survived to age 3 years and reviewed the outcome of other reported survivors (approximately 14% of reported cases). Survivors tended to have less frequent diaphragmatic hernia, milder lung hypoplasia, absence of complex cardiac malformation, and severe neurologic impairment. Their patient had malformations of gyration and sulcation, particularly around the central sulcus, and hypoplastic optic tracts beyond the optic chiasm associated with profound mental retardation.

- Fryns and Moerman (1998) reported a second-trimester male fetus with Fryns syndrome and midline scalp defects. The authors stated that the finding of a scalp defect in Fryns syndrome confirms that it is a true malformation syndrome with major involvement of the midline structures.

- Ramsing et al. (2000) described 2 sibships with 4 fetuses and 1 preterm baby of 31 weeks' gestation affected by a multiple congenital disorder suggestive of Fryns syndrome. In addition to the diaphragmatic defects and distal limb anomalies, they presented with fetal hydrops, cystic hygroma, and multiple pterygias. Two affected fetuses in 1 family showed severe craniofacial abnormalities with bilateral cleft lip and palate and cardiovascular malformation.

- Arnold et al. (2003) reported a male fetus with Fryns syndrome and additional abnormalities, in particular, multiple midline developmental defects including gastroschisis, central nervous system defects with left arrhinencephaly and cerebellar hypoplasia, midline cleft of the upper lip, alveolar ridge, and maxillary bone, and cleft nose with bilateral choanal atresia.

- Pierson et al. (2004) reviewed 77 reported patients with Fryns syndrome and summarized the abnormal eye findings identified in 12 of them. They also described 3 new patients with Fryns syndrome, 1 of whom demonstrated unilateral microphthalmia and cloudy cornea.

- Slavotinek et al. (2005) noted that Fryns syndrome may be the most common autosomal recessive syndrome in which congenital diaphragmatic hernia (see DIH2, 222400) is a cardinal feature. The autosomal recessive inheritance in Fryns syndrome contrasts with the sporadic inheritance for most patients with DIH.