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It is possible that the main title of the report Cerebellar Agenesis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
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Cerebellar agenesis is an extremely rare condition. Cerebellar agenesis is a descriptive term implying complete absence of the cerebellum, irrespective of its underlying cause (etiology). Usually, small remnants of the cerebellum are present; therefore the term subtotal cerebellar agenesis is also used in the literature. It is now recognized that cerebellar agenesis can represent a primary disturbance of embryonic development (also called malformation), but it can also result from a secondary destruction of normally developed tissue (also called a disruption). (See the Causes section below for additional information). It is now established that the cerebellum is not only responsible for motor coordination (of muscles, the trunk and limbs, the tongue, and the eye muscles), but also plays an important role in many non-motor functions, including learning, memory, language, and behavior. Therefore, individuals with congenital as well as acquired cerebellar disorders often have learning disabilities, impaired executive functions, and variable degree of cognitive impairments.
The signs and symptoms of cerebellar agenesis can vary greatly from one individual to another. According to the medical literature, some individuals with cerebellar agenesis have had only mild symptoms. In fact, in some reported cases, it has been claimed that motor function may be almost normal, perhaps due to partial compensation from other areas of the brain. Reports in the medical literature discuss individuals with cerebellar agenesis who had a normal lifespan, attended regular schools and found employment and lived productive though often "simple" lives.
Additional reports have noted individuals with cerebellar agenesis whose mental capacities were unaffected and who did not exhibit any symptoms of cerebellar agenesis (asymptomatic cases). However, other researchers have disputed these claims, stating that in virtually all of cases of cerebellar agenesis there have been observable symptoms including profound abnormalities in motor skills. Most likely, cerebellar agenesis represents a spectrum of disease that may range from those with severe disability to those with milder expressions of the disorder.
It is important to note that the symptoms of cerebellar agenesis are extremely variable and that affected individuals may not have all of the symptoms discussed below. Affected individuals or parents of affected children should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
Cerebellar agenesis is most often associated with impairment of motor function, especially an inability to coordinate of voluntary movements (ataxia). Affected individuals may be clumsy and there may be delays in the acquisition of motor activities (psychomotor delays). Walking may be delayed until 4-7 years of age. Cerebellar agenesis may also be associated with low muscle tone (hypotonia).
In some cases, affected individuals may have difficulty speaking usually due to problems with the muscles that enable speech (dysarthria). The ability to speak is usually delayed, sometimes significantly. Some individuals may exhibit rapid, involuntary movements of the eyes (nystagmus).
Intelligence may be unaffected. However, some affected individuals may display mild to moderate cognitive impairment. Some individuals with cerebellar agenesis have exhibited intellectual disability, but normal or near-normal motor skills.
In addition to affecting motor skills, damage to the cerebellum has also been associated with abnormalities of non-motor functions. Cerebellar dysfunction may also be associated with abnormalities of visuospatial abilities, expressive language, working memory and affective behavior.
As already mentioned in the General Discussion section, the etiology of cerebellar agenesis is not uniform, but varied (heterogeneous). Acquired (prenatal/perinatal) causes include cerebellar destruction caused by hemorrhage, lack of or diminished blood flow (ischemia), or other factors. This has been documented in a minority of children with spina bifida (myelomeningocele). It is being increasingly recognized in premature babies with very low birth weight, and is often accompanied by additional anomalies of the brain.
The exact cause of isolated cerebellar agenesis often remains unknown. Most cases occur randomly for unknown reasons (sporadically).
A genetic cause is only documented in an extremely rare syndrome of cerebellar agenesis and agenesis of the pancreas, resulting in neonatal diabetes mellitus. This syndrome is caused by mutations in the PTF1A gene, and it is inherited in an autosomal recessive manner.
Cerebellar agenesis appears to affect males and females in equal numbers. The exact incidence and prevalence of the disorder in the general population is unknown. Congenital isolated cerebellar agenesis is considered an extremely rare occurrence.
Cerebellar agenesis is defined by neuroimaging, and should not be confused with other more prevalent malformations of the cerebellum (e.g. Dandy-Walker malformation and Joubert syndrome) if the detailed neuroimaging pattern is taken into account.
Cerebellar agenesis can be interpreted as the most severe end of the spectrum of cerebellar hypoplasia, a general term for a cerebellum of diminished volume. Again, careful analysis of neuroimaging allows distinction form cerebellar hypoplasia, which is a very heterogeneous condition.
After birth (postnatally) the definite diagnosis of cerebellar agenesis is based on the neuroimaging findings, preferably MRI (magnetic resonance imaging); it cannot be made on clinical grounds. Before birth (prenatally) the diagnosis of cerebellar agenesis is not reliably possible, by ultrasound of fetal MRI. Babies are on record with normal brain ultrasound at 20-25 weeks of gestation, with subsequent destruction of the cerebellum.
The treatment of cerebellar agenesis is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, speech pathologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child's treatment.
Early intervention is important in ensuring that children with cerebellar abnormalities reach their highest potential. Services that may be beneficial may include physical therapy, occupational therapy and speech therapy. In some cases, special remedial education may be of benefit. Adaptive devices may assist individuals with significant motor deficits or speech difficulties.
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For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Poretti A, Boltshauser E, Schmahmann JD. Cerebellar agenesis. In: Cerebellar disorders in children. Boltshauser E and Schammann JD, Eds. 2012 Mac Keith Press, London. pp.117-121
Boltshauser E. Cerebellar Hypoplasias. In: Handbook of Clinical Neurology, Aminoff MJ, Boller F, Swaab DF, Eds. 2008 Elsevier, Radarweg, Amsterdam. pp. 115-126.
Stevenson RE, Hall JG, Eds. Human Malformation and Related Anomalies. 2nd ed. Oxford University Press, New York, NY;2006:667.
Lemon RN, Edgley SA. Life without a cerebellum. Brain. 2010;133:649-654.
Boyd CAR. Cerebellar agenesis revisited. Brain. 2010;133:941-944.
Huissoud C, Rudigoz RC, Bisch C, et al. Complete cerebellar agenesis: a very rare abnormality of the posterior fossa. Ultrasound Obstet Gynecol. 2009;33:73-734.
Poretti A, Prayer D, Boltshauser E. Morphological spectrum of prenatal cerebellar disruptions. Eur J Paed Neurol. 2009;13:397-407
Sellik GS, Barker KT, Stolte-Dijkstra I, et al. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet. 2008;36:1301-1305.
Miller KJ, Gleeson JG. Cerebellar development and disease. Curr Opin Neurobiol. 2008;18:12-19.
Tavano A, Grasso R, Gagliardi C, et al. Disorders of cognitive and affective development in cerebellar malformations. Brain. 2007;130:2646-2660.
Titomanlio L, Romano A, Del Giudice E. Cerebellar agenesis. Neurology. 2005;64:E21.
Richter S, Dimitrova A, Hein-Kropp C, et al. Cerebellar agenesis II: motor and language functions. Neurocase. 2005;11:103-113.
Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective disorder. J Neurophyschiatry Clin Neurosci. 2004;16:367-378.
Timmann D, Dimitrova A, Hein-Kropp C, Wilhelm H, Dorfler A. Cerebellar agenesis: clinical, neuropsychological and MR findings. Neurocase. 2003;9:402-413.
Leestma JE, Torres JV. Unappreciated agenesis of cerebellum in an adult: care report of a 38-year-old man. Am J Forensic Med Pathol. 2000;21:155-161.
Sener RN. Cerebellar agenesis versus vanishing cerebellum in Chiari II malformations. Comput Med Imaging Graph. 1995;19:491-494
Glickstein M. Cerebellar agenesis. Brain. 1994;117:1209-1212.
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Last Updated: 7/30/2012
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