Joubert's syndrome is a well-known but rare, autosomal-recessive condition. The clinical symptoms in Joubert syndrome are variable, and it is unknown whether it represents a clinically uniform disease entity. Irregular breathing in the neonatal period, developmental delay, mental retardation, hypotonia, ocular motor abnormalities, and, occasionally, retinal dystrophy and cystic kidneys are the main features of this syndrome. It is associated with cerebellar malformation. Vermis hypoplasia or agenesis and abnormalities at the pontomesencephalic junction are the hallmarks of the diagnosis, yet the relationship between radiologic and clinical findings has been targeted in only a few studies.
INPP5E gene was identified to be associated with Joubert's syndrome 1.
Sztriha et al. (1999) analyzed 6 patients, 5 males and one female, from two consanguineous (first cousins) Omani families with Joubert syndrome. In the first family, the parents had 11 children including 4 affected children; 3 males and one female. A 12th male child died at 6 years of age. He had severe delay in mental and motor development, and it is likely that he was also affected by the syndrome. No other affected members were observed in the extended family. The second family included two male patients with no history of a neurologic disorder in the family. All patients were born at term after uneventful pregnancies. Their neonatal period was normal. However, all acquired impairment of smooth pursuit and saccades. They preferred to move their heads when changing fixation (ocular motor apraxia), but all had a normal vestibule-ocular reflex. All patients had a malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa.
Saar et al. (1999) performed a whole-genome scan in the first family previously studied by Sztriha et al. (1999) and linkage to a localized locus responsible for Joubert syndrome was tested in another Omani family. In the first family, fluorescence-based semi-automated genotyping was done with analysis of 358 markers which covered the entire autosomal genome. With the assumption of autosomal recessive inheritance with full penetrance and equal allele frequencies for each marker, all markers were scored for homozygosity and all the genotypes were checked for Mendelian segregation which was followed by haplotyping. All four patients were found to be homozygous by descent for a single region on the telomeric region of chromosome 9q and all patients were found to be homozygous for three consecutive markers in the interval between D9S114 and D9S1838. On two-point and multipoint analysis, the family was linked to D9S158 (score of Z=+2.907 and +3.7, respectively). Saar et al. (1999) extended their analysis to the second family of Sztriha et al. (1999) to test it for possible linkage to the candidate region on chromosome 9. Upon analysis of the second family, the patients were found to be compatible with the linkage to the identified region as they had the same haplotype for five consecutive markers between D9S164 and D9S1838, and marker D9S158 had a two-point lod score of + 4.14. However, Saar et al. (1999) did not perform a whole-genome scan for this family and the possibility remains that the disease in the corresponding patients may be linked to another region. Saar et al. (1999) demonstrated genetic heterogeneity of this disorder and suggested further classification of Joubert syndrome based on linkage to chromosome 9qtel or the lack thereof.
[See also: UAE > Ben-Salem et al., 2014].
Sztriha et al. (1999) analyzed a 7-year-old male with Joubert syndrome born to consanguineous parents of Palestinian origin. During the neonatal period, the patient had episodic hyperpnea. He also had impairment of smooth pursuit and saccades as well as abnormal jerky eye movements from early infancy, which consisted of conjugate, irregular, pendular, rotatory, and horizontal movements. The entire vermis was absent. Sztriha et al. (1999) also observed malformation of the pontomesencephalic junction, with prominent superior cerebellar peduncles and deep interpeduncular fossa in the patient. Subsequently, Saar et al. (1999) tested DNA samples of the family for possible linkage to a candidate region on chromosome 9. Haplotype analysis excluded linkage for this region in the family, since the patients shared both parental chromosomes with one of their healthy sisters.
Alorainy (2006) reviewed and analyzed the MRI studies on 808 pediatric patients (aged 3 days to 15 years) over a 3-year period. A total of 114 congenital cerebral malformations were identified in 86 of these patients via MRI. Three patients were identified with Joubert Syndrome, two of whom were siblings.
Al Talabani et al. (1998) studied the pattern of major congenital malformations in 24,233 consecutive live and stillbirth at Corniche hospital, which is the only maternity hospital in Abu Dhabi, between January 1992 and January 1995. A total of 401 babies (16.6/1,000), including 289 Arabs, were seen with major malformation. Single gene disorders accounted for 24% of the cases, 76% were due to autosomal recessive disorders. In their study, Al Talabani et al. (1998) observed one case of Joubert syndrome born to a first cousin couple from the United Arab Emirates. Recurrence was reported in the family. Al Talabani et al. (1998) concluded that their study was very close to representing the true incidence of congenital abnormalities in the whole United Arab Emirates, as they investigated over 98% of deliveries in Abu Dhabi, the capital of United Arab Emirates.
Ben-Salem et al. (2014) reported an Emirati patient of Omani origin with Joubert Syndrome. The patient was born to consanguineous parents. Molecular analysis identified a mutation in the INPP5E gene.
[See also: Oman > Sztriha et al. (1999), Saar et al. (1999); Palestine > Sztriha et al. (1999), Saar et al. (1999)].