Joubert Syndrome and Related Disorders

Implications for Nurse Practitioners

Laurie Anne Ferguson, FNP-C; Maritza Salgado, FNP-BC


Journal for Nurse Practitioners. 2012;8(4):316-322. 

In This Article

Genotype and Phenotype Associations

Two classic methods are used in the study of genetics and inheritance. The first is linkage analysis and is family based, which includes the review of family pedigrees to study disease patterns. Linkage analysis screens the entire genome and aims to discover the location of the causative gene(s). The assumption is made that family members with the disease phenotype have the affected allele or genotype.

The other approach is association analysis, which is population based.[5] Since JSRD is so rare, the population-based approach is challenging in terms of finding the causative genes associated with the syndrome. The population-based approach focuses on examining the frequency of a specific allele or genotype in patients versus those in controls. In other words, the purpose of association analysis is to determine the causative gene.[6]

The classic radiographic findings of absent or severely underdeveloped cerebellar vermis with its classic "molar tooth sign" (MTS), along with the typical neurologic signs of hypotonia, ataxia, and developmental delay, are used to diagnose patients with JSRD. Genetic causality has been less clear because of genetic overlap in clinical symptoms and syndromes. The first JSRD locus on chromosome 9q was identified as recently as 1999. All the current genes associated with JSRD encode for proteins, which are expressed in the primary cilium or the centrosome.

Primary cilia are structures found in several tissues, including renal tubules, bile ducts, retinal photoreceptors, and neuronal cells in both the fetal and adult brain. Cilia act like sensors and are involved in both the development and accurate function of such organs as kidneys, brains, eyes, and liver. Ciliopathies or abnormalities in the cilia may explain why there is an overlap between JSRD and other genetic disorders with common gene expressions and is an emerging field of genetic research.[7] While there has been remarkable progress in explaining the genetic basis of JSRD and identifying genes, it appears that all these genes explain for only 25% of JSRD families.[7] No curative genetic therapies exist for these ciliopathic syndromes.[8]


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