Joubert syndrome

background

Joubert syndrome and related disorders (JSRD) are a spectrum of disorders that have some, but not all, features in common. Joubert syndrome is a rare genetic condition that affects the cerebellar vermis, which is found between the left and right hemispheres of the cerebellum and controls balance and coordination. In Joubert syndrome, the cerebellar vermis is absent or underdeveloped and the brain stem is malformed. These brain abnormalities are called the "molar tooth sign," because the structures look like a molar tooth on a magnetic resonance imaging (MRI) scan. The most common features of the disorder are ataxia (a lack of muscle control), hyperpnea (an abnormal breathing pattern characterized by rapid breathing), sleep apnea, intellectual disabilities, and involuntary eye and tongue movements. Other abnormalities, such as extra fingers or toes, a cleft lip or palate, tongue abnormalities, and seizures, may occur. The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal.
Most cases of Joubert syndrome occur in individuals with no family history of the disorder. These cases are caused by a spontaneous genetic mutation in the egg, sperm cells, or developing embryo. In some cases, Joubert syndrome is inherited, or passed down among family members. Joubert syndrome is more likely to occur in consanguineous families, in which the parents are closely related and the faulty gene runs in the family. When Joubert syndrome is inherited, it follows an autosomal recessive pattern of inheritance.
The prevalence of Joubert syndrome is unknown, but more than 200 cases have been reported in people of Algerian, Belgian, Dutch, French Canadian, German, Indian, Italian, Japanese, Laotian, Moroccan, Portuguese, Spanish, Swedish, Swiss, and Turkish origin. Males are twice as likely to have Joubert syndrome as females, for unknown reasons.
There is no cure for Joubert syndrome. Treatment aims to reduce symptoms and prevent complications. Prognosis depends on the severity of damage to the cerebellar vermis. Some people with Joubert syndrome are only mildly affected while others are more severely affected.

Related Terms

AHI1, CEP290, cerebellar vermis agenesis-hyperpnea-episodic eye moves-ataxia-retardation, cerebellar vermis aplasia, cerebellarparenchymal disorder IV, cerebello-oculo-renal syndrome 1 (CORS1), cerebelloparenchymal disorder IV (CPD4), cerebelloparenchymal disorder IV familial, chorioretinal coloboma-Joubert syndrome, COACH, Dekaban-Arima syndrome, hyperpnea-episodic abnormal eye movement, JBTS1, Joubert-Boltshauser syndrome, kidneys-cystic retinal aplasia Joubert syndrome, NPHP1, polydactyly-Joubert syndrome, retinal aplastic-cystic kidneys-Joubert syndrome, Senior-Løken syndrome, TMEM67(MKS3), Varadi-Papp syndrome, vermis aplasia, vermis cerebellar agenesis.

types of the disease

Joubert syndrome and related disorders (JSRD) are a spectrum of disorders that have some, but not all, features in common. The fundamental feature of the "molar tooth sign," seen on specific views of a brain scan, is a critical step in making a diagnosis of Joubert syndrome. Other features, such as kidney problems, eye or retinal changes, and liver problems, are likely to be specific to certain JSRD subgroups, including Joubert syndrome, Dekaban-Arima syndrome, Senior-Løken syndrome, Varadi-Papp syndrome, and COACH.
Joubert syndrome: Joubert syndrome is a rare genetic condition that affects the cerebellar vermis, the part of the brain that controls balance and coordination and is found between the left and right sides of the brain. In Joubert syndrome, the cerebellar vermis is absent or underdeveloped, and the brain stem is malformed. These brain abnormalities are called the "molar tooth sign," because these structures look like a molar tooth on a magnetic resonance imaging (MRI) scan. The most common features of the disorder are ataxia (a lack of muscle control), hyperpnea (an abnormal breathing pattern characterized by rapid breathing), sleep apnea, intellectual disabilities, and involuntary eye and tongue movements. Other abnormalities, such as extra fingers or toes, a cleft lip or palate, tongue abnormalities, and seizures, may occur. Four causative genes, which appear to account for no more than 10% of cases of Joubert syndrome each, are NPHP1, CEP290, AHI1, and TMEM67 (MKS3); other causative genes are unknown.
Dekaban-Arima syndrome: Dekaban-Arima syndrome is a related disorder with visual deficiency and renal insufficiency that is characterized by an abnormality in the cerebellar vermis, a part of the brain. Symptoms associated with this disorder may include developmental delays, intellectual disabilities, and breakdown of the retina, which may lead to blindness. Some children may demonstrate repeated eye rubbing, poking, and pressing (symptoms of severe visual impairment); decreased kidney function; hypotonia (decreased muscle tone); and short stature and poor growth. Dekaban-Arima syndrome is passed down from parents to offspring as an autosomal recessive trait, meaning that an individual must inherit a copy of the defective gene from each parent in order for the condition to occur. The likelihood of having a child with Dekaban-Arima syndrome for parents who carry the altered gene is one in four, or 25%, in each pregnancy that they share. To date, no genes known to be specifically responsible for Dekaban-Arima syndrome have been identified. However, it is possible that mutations in the CEP290 gene, one of the three genes identified for JSRD thus far, may cause Dekaban-Arima syndrome in some children. However, this gene is not the cause in many individuals with JSRD, and the genetics of these disorders remains complex and unknown.
Senior-Løken syndrome: Senior-Løken syndrome is a disorder with a combination of nephronophthisis with retinal dystrophy. Symptoms of Senior-Løken syndrome include renal insufficiency, particularly juvenile nephronophthisis. Initial symptoms of nephronophthisis include increased thirst, urination, and sometimes anemia and breakdown of the retina, which may lead to blindness. Reduced ability to see well in low-light conditions (e.g., at night) may be one of the first indications of retinal dystrophy. Senior-Løken syndrome is passed down from parents to offspring as an autosomal recessive trait, meaning that an individual must inherit a copy of the defective gene from each parent in order for the condition to occur. The likelihood of having a child born with Senior-Løken syndrome for parents who carry the altered gene involved is one in four, or 25%, in each pregnancy that they share. A number of genes responsible for Senior-Løken syndrome have been identified, and some of these genes are altered in those individuals who have associated features of a cerebellar malformation and developmental delays. Three such genes associated with Joubert syndrome and complications of retinal dystrophy and nephronophthisis are NPHP1, AHI1, and CEP290. However, these do not explain all cases of Senior-Løken syndrome, and the genetics of these disorders remains complex and unknown.
Varadi-Papp syndrome: Varadi-Papp syndrome, a related disorder, is a type of oral-facial-digital (OFD) disorder characterized by an abnormality in the cerebellar vermis, a part of the brain. Individuals diagnosed with Varadi-Papp syndrome traditionally exhibit the following features: cleft lip or palate; anomalies of the tongue, such as nodules or benign tumors; oral frenula (extra strands of tissue between the gums, and in the tongue and mouth); abnormalities in teeth, particularly tooth shape and tooth enamel hypoplasia; facial abnormalities, including abnormalities in the region of the eyes, which may include epicanthal folds (prominent folds of skin over the central corners of the eye), squinting, strabismus (paralysis of the ocular muscles), or hypertelorism (wide-spaced eyes); and polydactyly (extra fingers and toes), especially of central digits (with a Y-shaped metacarpal bone in the hands), and duplicated great toes. Other symptoms include extra digits on the pinkie side of the hand; a variety of brain malformations, such as an underdeveloped cerebellar vermis (called hypoplasia) or complete lack of the cerebellar vermis (called aplasia or agenesis), which may be indicated by the "molar tooth" sign found on axial views on an MRI scan; developmental delays and intellectual disabilities; and short stature and poor growth. Varadi-Papp syndrome is passed from parent to offspring as an autosomal recessive trait, meaning that an individual must inherit a copy of the defective gene from both parents in order for the condition to occur. The likelihood of having a child born with this condition for parents who carry the gene involved is one in four, or 25%, in each pregnancy that they share. To date, no genes known to be responsible specifically for Varadi-Papp syndrome have been identified. Although three genes are known to cause JSRD, none of these has been associated with the features of Varadi-Papp syndrome.
Cogan-type congenital oculomotor apraxia (Cogan-type OMA): Cogan-type congenital oculomotor apraxia (Cogan-type OMA) is a related disorder. OMA refers to a specific eye movement caused by an abnormality in the cerebellar vermis, a part of the brain, because of which it is difficult for children to track objects smoothly. Their eyes may appear to jump, with jerky movements. Symptoms are congenital (present from birth). Cogan-type OMA is believed to be passed down from parents to offspring as an autosomal recessive trait, meaning that an individual must inherit a copy of the defective gene from both parents in order for the condition to occur. The likelihood of having a child born to parents who carry the altered gene involved is one in four, or 25%, in each pregnancy that they share. One gene for this disorder has been identified, NPHP1, but it is unclear whether this gene is altered only in those individuals who have associated features of nephronophthisis, a cerebellar malformation, or both. It is likely that alterations in other genes also may cause this condition.
COACH: COACH is a related disorder characterized by an abnormality in the cerebellar vermis, a part of the brain. The name COACH is a mnemonic that stands for the different characteristics of the disorder: cerebellar vermis hypoplasia/aplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis. Patients diagnosed with COACH traditionally exhibit the following features: hypoplasia (underdevelopment) or aplasia/agenesis (complete lack) of the cerebellar vermis, usually indicated by the "molar tooth" sign found on an axial view of an MRI scan; developmental delays or intellectual disabilities; difficulty coordinating voluntary muscle movements; ataxia (uncoordinated movements); coloboma (a malformation of the retina or other regions of the eye); abnormalities of the liver, including hepatic fibrosis, which have delayed onset or progress slowly; and hypotonia (decreased muscle tone). COACH syndrome is passed down from parents to offspring as an autosomal recessive trait, meaning that an individual must inherit a copy of the defective gene from both parents in order for the condition to occur. The likelihood of having a child born with COACH for parents who carry the altered gene involved is one in four, or 25%, in each pregnancy that they share. To date, no genes have been identified that cause COACH syndrome specifically. It is likely that alterations in multiple genes may cause this condition.