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Familial aplasia of the vermis(CPD4; JBTS)

MedGen UID:
98464
Concept ID:
C0431399
Disease or Syndrome
Synonyms: Cerebelloparenchymal disorder 4; CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Joubert-Boltshauser syndrome
SNOMED CT: Joubert syndrome (716997004); Familial aplasia of the vermis (253175003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Genes (locations): CEP41 (7q32.2); CPLANE1 (5p13.2); RPGRIP1L (16q12.2); TCTN2 (12q24.31); TCTN3 (10q24.1); TMEM138 (11q12.2); TMEM231 (16q23.1); TMEM237 (2q33.1); TTC21B (2q24.3)
Related genes: KIF7, ARL13B, TMEM67, CEP290, TCTN1, CC2D2A, INPP5E, AHI1, TMEM216, OFD1, NPHP1
 
Monarch Initiative: MONDO:0018772
OMIM®: 213300
OMIM® Phenotypic series: PS213300
Orphanet: ORPHA475

Disease characteristics

Excerpted from the GeneReview: Joubert Syndrome
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen. [from GeneReviews]
Authors:
Melissa Parisi  |  Ian Glass   view full author information

Additional description

From MedlinePlus Genetics
Joubert syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.

The hallmark feature of Joubert syndrome is a combination of brain abnormalities that together are known as the molar tooth sign, which can be seen on brain imaging studies such as magnetic resonance imaging (MRI). This sign results from the abnormal development of structures near the back of the brain, including the cerebellar vermis and the brainstem. The molar tooth sign got its name because the characteristic brain abnormalities resemble the cross-section of a molar tooth when seen on an MRI.

Most infants with Joubert syndrome have low muscle tone (hypotonia) in infancy, which contributes to difficulty coordinating movements (ataxia) in early childhood. Other characteristic features of the condition include episodes of unusually fast (hyperpnea) or slow (apnea) breathing in infancy, and abnormal eye movements (ocular motor apraxia). Most affected individuals have delayed development and intellectual disability, which can range from mild to severe. Distinctive facial features can also occur in Joubert syndrome; these include a broad forehead, arched eyebrows, droopy eyelids (ptosis), widely spaced eyes (hypertelorism), low-set ears, and a triangle-shaped mouth.

Joubert syndrome can include a broad range of additional signs and symptoms. The condition is sometimes associated with other eye abnormalities (such as retinal dystrophy, which can cause vision loss, and coloboma, which is a gap or split in a structure of the eye), kidney disease (including polycystic kidney disease and nephronophthisis), liver disease, skeletal abnormalities (such as the presence of extra fingers and toes), or hormone (endocrine) problems. A combination of the characteristic features of Joubert syndrome and one or more of these additional signs and symptoms once characterized several separate disorders. Together, those disorders were referred to as Joubert syndrome and related disorders (JSRD). Now, however, any instances that involve the molar tooth sign, including those with these additional signs and symptoms, are usually considered Joubert syndrome.  https://medlineplus.gov/genetics/condition/joubert-syndrome

Professional guidelines

PubMed

Spahiu L, Behluli E, Grajçevci-Uka V, Liehr T, Temaj G
J Mother Child 2022 Mar 1;26(1):118-123. Epub 2023 Feb 22 doi: 10.34763/jmotherandchild.20222601.d-22-00034. PMID: 36803942Free PMC Article
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Ultrasound Obstet Gynecol 2021 Dec;58(6):864-874. doi: 10.1002/uog.23660. PMID: 33942916

Curated

Valente EM, Brancati F, Boltshauser E, Dallapiccola B
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Mar 30 doi: 10.1038/ejhg.2011.49. PMID: 21448235Free PMC Article

American College of Medical Genetics ACT Sheet, Carrier Screening ACT Sheet Ashkenazi Jewish Genetic Disorders

Recent clinical studies

Therapy

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Prognosis

Gana S, Serpieri V, Valente EM
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Society for Maternal-Fetal Medicine (SMFM), Monteagudo A
Am J Obstet Gynecol 2020 Dec;223(6):B38-B41. Epub 2020 Nov 7 doi: 10.1016/j.ajog.2020.08.184. PMID: 33168220
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Clinical prediction guides

Schröder S, Yigit G, Li Y, Altmüller J, Büttel HM, Fiedler B, Kretzschmar C, Nürnberg P, Seeger J, Serpieri V, Valente EM, Wollnik B, Boltshauser E, Brockmann K
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J Med Genet 2015 Aug;52(8):514-22. Epub 2015 Jun 19 doi: 10.1136/jmedgenet-2015-103087. PMID: 26092869Free PMC Article

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