Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa. The syndrome was first identified in 1969 by pediatric neurologist Marie Joubert in Montreal, Quebec, Canada, while working at the Montreal Neurological Institute and McGill University. Signs and symptoms
Most of the signs and symptoms of the Joubert syndrome appear very early in infancy with most children showing delays in gross motor milestones. Although other signs and symptoms vary widely from individual to individual, they generally fall under the hallmark of cerebellum involvement or in this case, lack thereof. Consequently, the most common features include ataxia (lack of muscle control), hyperpnea (abnormal breathing patterns), sleep apnea, abnormal eye and tongue movements, and hypotonia in early childhood. Other malformations such as polydactyly (extra fingers and toes), cleft lip or palate, tongue abnormalities, and seizures may also occur. Developmental delays, including cognitive, are always present to some degree. Severe forms have been noted to include hypoplasia of the corpus callosum.Those with this syndrome often exhibit specific facial features such as a broad forehead, arched eyebrows, ptosis (droopy eyelids), hypertelorism (widely spaced eyes), low-set ears and a triangle shaped mouth. Additionally, this disease can include a broad range of other abnormalities to other organ systems such as retinal dystrophy, kidney diseases, liver diseases, skeletal deformities and endocrine (hormonal) problems.
The relative proportions of the two zones can vary within different areas of a tumor and between tumors. Immunohistochemical analyses indicate that the spindle-shaped cells strongly express smooth muscle actin, calponin, and, less commonly, desmin proteins. Gene abnormalities
Familial IMF
Twenty families with inherited IMF have been shown to have mutations in one of their two PDGFRB genes. The PDGFRB gene is located in band 32 on the long (or "q") arm of chromosome 5. Of the 20 families with PDGFRB gene mutations, 15 carried a p.Arg561Cys mutation. This mutation substitutes the amino acid Arg, i.e. arginine, for the amino acid cystine at the 561st amino acid position as numbered starting at the N-terminus of the genes product protein, the PDGFβ receptor. Four of the remaining families carried either a p.Pro560Leu (Pro=proline, Leu=leucine); p.Arg561Ser (Ser=serine); p. Lys567Glu (Lys=lysine, Glu=glutamate); or p.Pro660Thr (Thr=threonine) mutation in this protein. The NOTCH3 gene (located in band 13.12 on the short (or "p") arm of chromosome 19) mutation in the carrier family was p. Leu1519Pro. The p.Arg561Cys, p.Pro560Leu, p.Arg561Ser, and p. Lys567Glu mutations are regarded as contributing to the development and/or progression of IMF while the p.Pro660Thr PDGFRB gene mutation and the p. Leu1519Pro NOTCH3 p. Leu1519Pro gene mutation require further study to determine more clearly their clinical significances. Non-familial IMF
Somatic PDGFRB gene mutations have been found in 29% of individuals with solitary IMF tumors and 68% of individuals with multiple tumors (with viscera involvement) plus multiple tumors (no visceral involvement) IMF.