1999-12-17-11 Joubert syndrome © Jeanty www.thefetus.net/
Philippe Jeanty, MD, PhD, Nashville, TN and Gianluigi Pilu, MD. Bologna, Italy
Marie Joubert described the syndrome in 1968  -69  . It is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation
The first ultrasonic diagnosis was made by Campbell in 1984  . The following findings have been found in fetus with Joubert syndrome  ,  :
- vermian agenesis
- abnormal cerebellar shape
- renal anomalies
- nuchal lucency 
Interestingly there is another report of a fetus in which the vermis was considered abnormal, had a normal postnatal examination and the diagnosis was only made later22 .
These are 9 images from 2 midtrimester exams (3 weeks apart) on a little baby boy. The spine was normal. The fetus was then referred elsewhere where he was considered normal. A CT at birth was also read as normal.
The images demonstrated a small degree of ventriculomegaly and an abnormal posterior fossa. The first six images do not demonstrate the vermis. Instead there is a great big cleft in between lateral lobes of the cerebellum.
Image 7 demonstrates a small amount of ventriculomegaly but also notice the appearance of the cerebellum: the "buttock sign"
3. Picture 8: mild ventriculomegaly
4. Picture 9 shows the cavum of the septi pellucidi, thus excluding dysgenesis of the corpus callosum.
A CT done after birth was read as normal. However, when the child was one year old, a geneticist put together the clinical findings of this baby and obtained a MRI:
Several axial views that demonstrate the absence of the vermis and the “molar tooth” sign (see below)
Coronal views with absence of the vermis and demonstration of the corpus callosum
Sagittal views with absence of the vermis and demonstration of the corpus callosum
The diagnosis is based on the clinical findings and supported by the pathognomonic “molar tooth” sign on MRI.
The recently described “molar tooth” sign on axial sections results from a combination of midbrain, vermian, and superior cerebellar peduncle abnormalities  . Other findings include  ,  :
- thinned optic tracts,
- enlarged temporal horns in the absence of hydrocephalus,
- high-signal of the cerebral periventricular white matter,
- abnormal signal in the decussation of the superior cerebellar peduncles,
- abnormal embryonic vessels associated with the dysplastic folia of the cerebellar hemispheres
- dilatation of the fourth ventricle with some appearing bat-wing shaped,
- elongation and stretching of the superior cerebellar peduncles,
- dysplasia of the vermis,
- widening of the foramen of Magendie and the posterior cistern
On postnatal diagnosis the following findings can be recognized  :
- molar tooth sign
- dysgenesis of the isthmic portion of the brain stem at the pontomesencephalic junction,
- abnormally thick superior cerebellar peduncles perpendicular to the brain stem,
- hypoplasia of the cerebellar vermis with enlargement of the 4th ventricle and rostral shift of the fastigium,
- sagittal vermis clefting
- mild prominence of the ventricles and subarachnoid spaces
Not all findings are present in all babies
- truncal ataxia
- developmental delay
- abnormal eye movements
- tongue protrusion
And less commonly  :
- hemifacial spasms
- polydactyly 8%
- colobomas 4%
- renal cysts 2%
- soft tissue tumors of the tongue2%
- occipital meningocele 
Siblings from the same family and even monozygotic twins  with Joubert syndrome may present with phenotypes ranging from severely handicapped to minimally handicapped. The motor handicap varies from wheelchair bound to being able to walk and run and the mental handicap from severely retarded, nonverbal, and autistic to verbal.
A recent report (this week) suggests that the anomaly is genetically heterogeneous and that one locus maps to the telomeric region of chromosome 9q, close to the marker D9S158, with a multipoint LOD score of Z=+3.7  .
The following cculomotor anomalies have been described  :
- decreased smooth pursuit gain
- hypometric volitional saccades
- optic nerve dysplasia
- severe visual loss
- oculomotor apraxia
- pendular nystagmus
- gaze-holding nystagmus
- pigmentary changes in the fundus
- decreased vestibulo-ocular reflexes
A variety of deficits in cognition, verbal memory, visuomotor, motor, and language-related tasks are described as well as problems in temperament, hyperactivity, aggressiveness, and dependency  . The degree of developmental delay (DG: 30-85)41 in Joubert syndrome and the severity of gross central nervous system malformations appear independent  . In one case there was no mental retardation  and in another marked improvement appeared after some delay  .
Other anomalies like ectodermal dysplasia  , Gaucher disease  , multicystic kidney disease, hepatic fibrosis  , hypertension  have also been associated.
A decreased life span has been found in many patients  .
The following anomalies have been reported  ,  :
- aplasia or agenesis of the cerebellar vermis
- fragmentation several brainstem nuclei (dentate nuclei, inferior olives, and basis pontis)
- dysplasia of structures at the pontomesencephalic junction and caudal medulla
- abnormal decussation of the superior cerebellar peduncles
- enlarged iter (rostral 4th ventricle)
- elongated tegmental nuclei (including the locus coeruleus)
- reduction of the neurons of the basis pontis and reticular formation
- malformations of the medulla (hypoplasia of the inferior olivary nuclei, solitary nuclei and tracts, and the nucleus and spinal tracts of trigeminal nerve (cranial nerve V).
- dysplasia of the caudal medulla at the cervicomedullary junction (absence of a posterior median sulcus, neuronal swelling and axonal spheroids in the region of malformed nuclei gracilis and cuneatus, and absence of pyramidal decussation)
Thus aside from vermal agenesis, Joubert syndrome may be associated with malformation of multiple brainstem structures. This could explain the hyperpnea and oculomotor anomalies.
Vermian cleft without Joubert  , Dandy-Walker, Dandy-Walker variant, Down’s syndrome 
There is a support group in the department of Marie Joubert and she can be contacted at : firstname.lastname@example.org . Other resource include the Joubert Syndrome Resource and Joubert Syndrome at the National Institute of Neurological Disorders and Stroke Kris, the mom of this baby just started another list at email@example.com .
In view of the few cases diagnosed there is not much support for parents of affected kids. It has been shown that the “parental burden depends more on the parents" coping skills and the level of family functioning rather than on the degree of the child"s impairment”  .
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