Joubert syndrome
Encyclopedia
Joubert syndrome is a rare genetic disorder
that affects the cerebellum
, an area of the brain
that controls balance and coordination.
and a malformed brain stem
(molar tooth sign). The most common features include ataxia
(lack of muscle control), hyperpnea
(abnormal breathing patterns), sleep apnea
, abnormal eye and tongue movements, and hypotonia
. Other malformations such as extra fingers and toes
, cleft lip or palate, tongue abnormalities, and seizure
s may also occur. There may be mild or moderate retardation. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa
. The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal
, Canada, while working at the Montreal Neurological Institute and McGill University
.
s that are mutated
in individuals with Joubert syndrome have been identified:
s, not previously thought to be related, may indeed be related as to their root cause. Joubert syndrome is one such disease. It is a member of an emerging
class of diseases called cilopathies
.
The underlying cause of the ciliopathies may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
, organelle
s which are present in many cellular types throughout the human
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases.
Currently recognized ciliopathies include Joubert syndrome, primary ciliary dyskinesia
, Bardet-Biedl syndrome
, polycystic kidney disease
and polycystic liver disease
, nephronophthisis
, Alstrom syndrome
, Meckel-Gruber syndrome and some forms of retinal degeneration
.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that affects the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
, an area of the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
that controls balance and coordination.
Diagnosis
The disorder is characterized by absence or underdevelopment of the cerebellar vermisCerebellar vermis
The cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
and a malformed brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
(molar tooth sign). The most common features include ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
(lack of muscle control), hyperpnea
Hyperpnea
Hyperpnea or hyperpnoea is increased depth of breathing when required to meet metabolic demand of body tissues, such as during or following exercise, or when the body lacks oxygen , for instance in high altitude or as a result of anemia....
(abnormal breathing patterns), sleep apnea
Sleep apnea
Sleep apnea is a sleep disorder characterized by abnormal pauses in breathing or instances of abnormally low breathing, during sleep. Each pause in breathing, called an apnea, can last from a few seconds to minutes, and may occur 5 to 30 times or more an hour. Similarly, each abnormally low...
, abnormal eye and tongue movements, and hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
. Other malformations such as extra fingers and toes
Polydactyly
Polydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
, cleft lip or palate, tongue abnormalities, and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s may also occur. There may be mild or moderate retardation. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa
Retinitis pigmentosa
Retinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
. The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal
Montreal
Montreal is a city in Canada. It is the largest city in the province of Quebec, the second-largest city in Canada and the seventh largest in North America...
, Canada, while working at the Montreal Neurological Institute and McGill University
McGill University
Mohammed Fathy is a public research university located in Montreal, Quebec, Canada. The university bears the name of James McGill, a prominent Montreal merchant from Glasgow, Scotland, whose bequest formed the beginning of the university...
.
Treatment
Treatment for Joubert syndrome is symptomatic and supportive. Infant stimulation and physical, occupational, and speech therapy may benefit some patients. Infants with abnormal breathing patterns should be monitored.Prognosis
The prognosis for individuals with Joubert syndrome varies. Some patients have a mild form with minimal motor disability and good mental development, while others may have severe motor disability and moderate mental retardation.Genetics
Multiple geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s that are mutated
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
in individuals with Joubert syndrome have been identified:
- JBTS3: Mutations in a gene of unknown function called AHI1AHI1Jouberin is a protein that in humans is encoded by the AHI1 gene.-Further reading:...
is associated with a subset of Joubert syndrome cases.
- JBTS4: In some rare cases of Joubert syndrome, mutations have been found in NPHP1NPHP1Nephrocystin-1 is a protein that in humans is encoded by the NPHP1 gene.-Interactions:NPHP1 has been shown to interact with BCAR1, PTK2B, Filamin and INVS.-Further reading:...
which is also associated with nephronophthisis, a cystic kidney disorder.
- JBTS5: The gene CEP290CEP290Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene.-External Links:* -Further reading:...
has been associated with both Joubert syndrome and Leber's congenital amaurosisLeber's congenital amaurosisLeber's congenital amaurosis is a rare inherited eye disease that appears at birth or in the first few months of life, and affects around 1 in 80,000 of the population.It was first described by Theodor Leber in the 19th century...
, type 10.
- TCTN2 and ATXN10 have been associated with Joubert syndrome.
| Type | OMIM | Gene |
|---|---|---|
| JBTS1 | INPP5E INPP5E 72 kDa inositol polyphosphate 5-phosphatase, also known as phosphatidylinositol-4,5-bisphosphate 5-phosphatase, is an enzyme that in humans is encoded by the INPP5E gene.- Function :INPP5E is an inositol 1,4,5-trisphosphate 5-phosphatase... |
|
| JBTS2 | TMEM216 TMEM216 Transmembrane protein 216 is a protein that in humans is encoded by the TMEM216 gene.- Clinical significance :Mutations in this gene may be associated with Meckel syndrome or Joubert syndrome.... |
|
| JBTS3 | AHI1 AHI1 Jouberin is a protein that in humans is encoded by the AHI1 gene.-Further reading:... |
|
| JBTS4 | NPHP1 NPHP1 Nephrocystin-1 is a protein that in humans is encoded by the NPHP1 gene.-Interactions:NPHP1 has been shown to interact with BCAR1, PTK2B, Filamin and INVS.-Further reading:... |
|
| JBTS5 | CEP290 CEP290 Centrosomal protein of 290 kDa is a protein that in humans is encoded by the CEP290 gene.-External Links:* -Further reading:... /NPHP6 |
|
| JBTS6 | TMEM67 TMEM67 Meckelin is a protein that in humans is encoded by the TMEM67 gene.- Function :The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium... |
|
| JBTS7 | RPGRIP1L RPGRIP1L RPGRIP1L is a human gene.-Function:The protein encoded by this gene is localized to primary cilia and centrosomes in ciliated human epithelial kidney cells... |
|
| JBTS8 | ARL13B ARL13B ADP-ribosylation factor-like protein 13B , also known as ADP-ribosylation factor-like protein 2-like 1, is a protein that in humans is encoded by the ARL13B gene.- Function :... |
|
| JBTS9 | CC2D2A CC2D2A Coiled-coil and C2 domain-containing protein 2A that in humans is encoded by tbe CC2D2A gene.-Function :This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation.... |
|
| JBTS10 | CXORF5 | |
| ?????? | ?????? | TCTN2 |
| ?????? | ?????? | ATXN10 ATXN10 Ataxin-10 is a protein that in humans is encoded by the ATXN10 gene.- Clinical significance :The autosomal dominant cerebellar ataxias are a clinically and genetically heterogeneous group of disorders characterized by ataxia, dysarthria, dysmetria, and intention tremor... |
Ciliopathy
Research has revealed that a number of genetic disorderGenetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s, not previously thought to be related, may indeed be related as to their root cause. Joubert syndrome is one such disease. It is a member of an emerging
Emergence
In philosophy, systems theory, science, and art, emergence is the way complex systems and patterns arise out of a multiplicity of relatively simple interactions. Emergence is central to the theories of integrative levels and of complex systems....
class of diseases called cilopathies
Ciliopathy
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosomes, it is possible for ciliopathies to be associated...
.
The underlying cause of the ciliopathies may be a dysfunctional molecular mechanism in the primary cilia structures of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
s which are present in many cellular types throughout the human
Human
Humans are the only living species in the Homo genus...
body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development and thus offer a plausible hypothesis for the often multi-symptom nature of a large set of syndromes and diseases.
Currently recognized ciliopathies include Joubert syndrome, primary ciliary dyskinesia
Primary ciliary dyskinesia
Primary ciliary dyskinesia , also known as immotile ciliary syndrome or Kartagener Syndrome ', is a rare, ciliopathic, autosomal recessive genetic disorder that causes a defect in the action of the cilia lining the respiratory tract and fallopian tube, and also of the flagella of sperm in...
, Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
, polycystic kidney disease
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
and polycystic liver disease
Polycystic liver disease
Polycystic liver disease usually describes the presence of multiple cysts scattered throughout normal liver tissue, in association with polycystic kidney disease.-Pathophysiology:Associations with PRKCSH and SEC63 have been described....
, nephronophthisis
Nephronophthisis
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease.The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.It is a form of...
, Alstrom syndrome
Alstrom syndrome
Alström syndrome is a rare genetic disorder caused by mutations in the gene ALMS1. It is among the rarest genetic disorders in the world, as currently it has only 266 reported cases in medical literature and over 501 known cases in 47 countries. It was first described by Carl-Henry Alström in...
, Meckel-Gruber syndrome and some forms of retinal degeneration
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
.