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org/rare-diseases/joubert-syndrome/
Joubert Syndrome
NORD gratefully acknowledges Joseph G. Gleeson, MD, Professor, Neurogenetics Laboratory,
Department of Neurosciences and Pediatrics; Investigator, Howard Hughes Medical Institute,
University of California, San Diego, for assistance in the preparation of this report.
Joubert-Bolthauser syndrome
General Discussion
Joubert syndrome is an autosomal recessive genetic disorder that affects the area of
the brain that controls balance and coordination. This condition is characterized by a
specific finding on an MRI called a "molar tooth sign" in which the cerebellar vermis
of the brain is absent or underdeveloped and the brain stem is abnormal. The most
common features of Joubert syndrome are lack of muscle control (ataxia), abnormal
breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements
and low muscle tone.
Causes
Joubert syndrome is inherited as an autosomal recessive genetic disorder.
Recessive genetic disorders occur when an individual inherits the same abnormal
gene for the same trait from each parent. If an individual receives one normal gene
and one gene for the disease, the person will be a carrier for the disease, but usually
will not show symptoms. The risk for two carrier parents to both pass the defective
gene and, therefore, have an affected child is 25% with each pregnancy. The risk to
have a child who is a carrier like the parents is 50% with each pregnancy. The
chance for a child to receive normal genes from both parents and be genetically
normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives
(consanguineous) have a higher chance than unrelated parents to both carry the
same abnormal gene, which increases the risk to have children with a recessive
genetic disorder.
Ten genes have been identified that cause Joubert syndrome. A mutation in the AHI1
(JBTS3) gene is responsible for this condition in approximately 11% of families.
Affected individuals with this gene mutation often have impaired vision due to retinal
dystrophy. A mutation in the NPHP1 (JBTS4) gene causes approximately 1-2% of
Joubert syndrome. Affected individuals with this gene mutation often develop a
progressive kidney disease called nephronophthisis. A mutation in the CEP290
(JBTS5) gene causes about 4-10% of Joubert syndrome. Mutations in the TMEM67
(JBTS6), JBTS1, JBTS2, JBTS7, JBTS8 and JBTS9 genes are also associated with
Joubert syndrome. Other genes responsible for this condition are currently unknown.
Affected Populations
The prevalence of Joubert syndrome has been estimated to be 1/258,000 but is
probably an underestimate of the true prevalence, which may be closer to 1/100,000.
Related Disorders
Several conditions have been described in which the molar tooth sign and
characteristics of Joubert syndrome are present in addition to other findings. It is not
yet clear if these conditions are variants of Joubert syndrome or separate
syndromes. The following conditions have been termed Joubert syndrome and
related disorders.
Dekaban-Arima syndrome is characterized by vision abnormalities and kidney
dysfunction.
Severe retinal dysplasia is characterized by blindness.
COACH syndrome is characterized by mental retardation, coloboma malformation of
the retina and liver abnormalities.
Senior-Loken syndrome is characterized by vision abnormalities and a type of kidney
dysfunction called nephronophthisis.
Varadi-Papp syndrome is also known as oral-facial-digital syndrome, type VI. This
condition is characterized by cleft lip or palate, tongue abnormalities, extra tissue
between the gums, tongue and mouth, dental abnormalities, facial abnormalities,
extra fingers and toes, poor growth and short stature.
Nephronophthisis is a specific type of kidney dysfunction.
Cogan oculomotor apraxia syndrome is characterized by an eye movement
abnormality.
Symptoms of the following disorders can be similar to those of Joubert syndrome.
Comparisons may be useful for a differential diagnosis:
Dandy-Walker malformation is a rare malformation of the brain that is present at birth
(congenital). It is characterized by an abnormally enlarged space at the back of the
brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid
through the openings between the ventricle and other parts of the brain. Excessive
amounts of fluid accumulate around the brain and cause abnormally high pressure
within the skull, swelling of the head (congenital hydrocephalus), and neurological
impairment. Motor delays and learning problems may also occur. Dandy-Walker
malformation is a form of obstructive or internal non-communicating hydrocephalus,
meaning that the normal flow of cerebrospinal fluid is blocked resulting in the
widening of the ventricles. (For more information, choose Dandy Walker as your
search term in the Rare Disease Database.)
Oral-facial-digital syndrome (OFDS) is an umbrella term for at least 10 apparently
distinctive genetic disorders that are characterized by defects and flaws in the
development of the structure of the oral cavity including the mouth, tongue, teeth,
and jaw; the development of the facial structures including the head, eyes, and nose;
and the fingers and toes (digits); along with differing degrees of mental retardation.
The presentation of signs and symptoms is extremely varied, making diagnosis
difficult. OFDS type I is the most common of all of these disorders, and it is quite
rare. Each of the other types is extremely rare. (For more information, choose oralfacial-digital as your search term in the Rare Disease Database.)
Meckel syndrome is a rare inherited disorder characterized by abnormalities
affecting several organ systems of the body (multisystem). Three classic symptoms
are normally associated with Meckel syndrome: protrusion of a portion of the brain
and its surrounding membranes (meninges) through a defect in the back or front of
the skull (occipital encephalocele), multiple cysts on the kidneys (polycystic kidneys),
and extra fingers and/or toes (polydactyly). Affected children may also have
abnormalities affecting the head and face (craniofacial area), liver, lungs, and
genitourinary tract. Meckel syndrome is inherited as an autosomal recessive trait.
(For more information, choose Meckel as your search term in the Rare Disease
Database.)
Diagnosis
The diagnosis of Joubert syndrome is based on physical symptoms and the molar
tooth sign as seen on an MRI. Molecular genetic testing is available for the four
genes that have been shown to cause Joubert syndrome in about 40% of cases.
Carrier testing and prenatal diagnosis are available if one of these gene mutations
has been identified in an affected family member.
Standard Therapies
Treatment
The treatment for Joubert syndrome is symptomatic and supportive. Developmental
delays are usually treated with physical therapy, occupational therapy, speech
therapy and infant stimulation. Individuals with Joubert syndrome should be
evaluated by appropriate specialists including nephrologists, ophthalmologists,
geneticists and neurologists. Annual screening is recommended for liver, kidney and
retinal abnormalities.
Genetic counseling is recommended for individuals with Joubert syndrome and their
families.
-----------------------------------------------Indonesia--------------------------------------------------------------Joubert Syndrome
Banyak gejala klinis sindrom Joubert yang jelas pada masa bayi dan anak-anak
yang paling terpengaruh memiliki keterlambatan dalam tonggak motorik kasar.
Fitur yang paling umum adalah kurangnya kontrol otot (ataksia), pola
pernapasan abnormal (hyperapnea), sleep apnea, gerakan mata dan lidah
abnormal dan otot rendah. Akal berkisar dari normal keterbelakangan mental
yang berat. Sindrom Joubert ditandai dengan temuan tertentu pada MRI disebut
"tanda gigi molar" di mana vermis serebelar otak tidak hadir atau terbelakang
dan batang otak tidak normal.
Sindrom Joubert adalah kondisi yang sangat variabel dan spektrum penuh gejala
belum ditentukan. Beberapa kondisi telah dijelaskan di mana "tanda gigi molar"
dan karakteristik sindrom Joubert yang hadir di samping temuan lainnya. Masih
belum jelas apakah kondisi ini varian sindrom Joubert atau sindrom terpisah.
Kondisi ini telah disebut "sindrom Joubert dan gangguan terkait". Beberapa
masalah lain yang mungkin terkait dengan sindrom Joubert termasuk kelainan
mata seperti perkembangan abnormal dari retina, kelainan pada iris (koloboma),
gerakan mata yang abnormal (nystagmus), mata juling (strabismus), dan
kelopak mata terkulai (ptosis) . Masalah lain kadang-kadang dikaitkan dengan
sindrom Joubert termasuk ginjal dan / atau hati kelainan, jari kaki ekstra
(polydactyly), celah di tengkorak dengan penonjolan selaput yang menutupi otak
(encephalocele) dan kelainan hormon.
Penyebab
Kelainan genetik resesif terjadi ketika seorang individu mewarisi gen abnormal
yang sama untuk sifat yang sama dari setiap orangtua. Jika seseorang menerima
satu gen normal dan satu gen untuk penyakit ini, orang tersebut akan menjadi
pembawa penyakit, tetapi biasanya tidak akan menunjukkan gejala. Risiko untuk
dua orang tua pembawa untuk kedua lulus gen yang rusak dan, oleh karena itu,
memiliki anak yang terkena adalah 25% dengan setiap kehamilan. Risiko untuk
memiliki anak yang merupakan pembawa seperti orang tua adalah 50% dengan
setiap kehamilan. Kesempatan bagi anak untuk menerima gen yang normal dari
kedua orang tua dan secara genetik yang normal untuk itu sifat tertentu adalah
25%. Risikonya adalah sama untuk pria dan wanita.
Semua individu membawa 4-5 gen abnormal. Orangtua yang kerabat dekat
(kerabat) memiliki kesempatan lebih tinggi dari orang tua yang tidak terkait
dengan kedua membawa gen abnormal yang sama, yang meningkatkan risiko
memiliki anak dengan kelainan genetik resesif.
Gangguan Terkait
Beberapa kondisi telah dijelaskan di mana "tanda gigi molar" dan karakteristik
sindrom Joubert yang hadir di samping temuan lainnya. Masih belum jelas
apakah kondisi ini varian sindrom Joubert atau sindrom terpisah. Kondisi berikut
telah disebut "sindrom Joubert dan gangguan terkait".
Senior-Loken sindrom ditandai oleh kelainan visi dan jenis disfungsi ginjal disebut
nephronophthisis.
Dandy-Walker malformasi adalah malformasi langka otak yang hadir pada saat
lahir (kongenital). Hal ini ditandai dengan ruang abnormal diperbesar di belakang
otak (ventrikel kistik 4) yang mengganggu aliran normal cairan serebrospinal
melalui bukaan antara ventrikel dan bagian lain dari otak. Jumlah cairan yang
berlebihan menumpuk di sekitar otak dan menyebabkan tekanan yang abnormal
tinggi di dalam tengkorak, pembengkakan kepala (hidrosefalus kongenital), dan
gangguan neurologis. Keterlambatan motorik dan masalah belajar juga dapat
terjadi. Dandy-Walker malformasi adalah bentuk obstruktif atau hidrosefalus nonberkomunikasi internal yang berarti bahwa aliran normal cairan serebrospinal
diblokir mengakibatkan pelebaran ventrikel. (Untuk informasi lebih lanjut, pilih
"Dandy Walker" sebagai istilah pencarian Anda dalam database Penyakit
Langka.)
gejala klasik yang biasanya terkait dengan sindrom Meckel: penonjolan sebagian
dari otak dan membran sekitarnya (meninges) melalui defek di bagian belakang
atau depan tengkorak (encephalocele oksipital), beberapa kista pada ginjal
(ginjal polikistik), dan jari tambahan dan / atau kaki (polydactyly). Anak yang
terkena mungkin juga memiliki kelainan yang mempengaruhi kepala dan wajah
(area kraniofasial), hati, paru-paru, dan saluran urogenital. Sindrom Meckel
diwariskan sebagai sifat resesif autosom. (Untuk informasi lebih lanjut, pilih
"Meckel" sebagai istilah pencarian Anda dalam database Penyakit Langka.)
Diagnosa
Diagnosis sindrom Joubert didasarkan pada gejala fisik dan "tanda gigi molar"
seperti yang terlihat pada MRI. Pengujian genetik molekular yang tersedia untuk
empat gen yang telah terbukti menyebabkan sindrom Joubert di sekitar 40%
kasus. Pengujian Carrier dan diagnosis prenatal yang tersedia jika salah satu dari
mutasi gen ini telah diidentifikasi dalam anggota keluarga yang terkena dampak.
Standar Terapi
Pengobatan