Ciliopathy

Ciliopathy refers to a group of genetic disorders caused by structural or functional abnormalities of cilia, small hair-like organelles that protrude from many cell types and act as signaling centers and cellular antennae. Primary cilia, present in most cells, coordinate signaling pathways such as Hedgehog, Wnt, and PDGFR, which are essential for development and tissue homeostasis. Ciliopathies arise from mutations in genes encoding ciliary proteins, affecting cilia formation, maintenance, or function. The resulting defects can affect multiple organs, leading to syndromic conditions with diverse clinical features, as well as nonsyndromic organ-specific diseases.

Well-known ciliopathies include autosomal recessive polycystic kidney disease, nephronophthisis, Joubert syndrome, Bardet-Biedl syndrome, Meckel-Gruber syndrome, and Alström syndrome. Common associated features include kidney disease with cystic changes, retinal dystrophy, obesity, liver fibrosis, polydactyly, brain malformations (such as molar tooth sign in Joubert syndrome), situs anomalies, and skeletal abnormalities. Because cilia are present in many tissues, manifestations vary widely even among individuals with mutations in the same gene.

Genetics and diagnosis: Most ciliopathies are inherited in an autosomal recessive manner, though some show autosomal dominant or X-linked patterns. More than a hundred genes have been implicated, including NPHP, BBS, CEP290, OFD1, and DYNC2H1. Diagnosis relies on clinical assessment, imaging, and genetic testing. Electron microscopy of cilia can show structural defects in some disorders, but molecular testing is central.

Management and prognosis: Treatment is supportive and multidisciplinary, addressing kidney, liver, eye, and neurological aspects. There is no cure for the ciliopathy itself; prognosis depends on severity and organ involvement. Research exploring ciliary biology and targeted therapies aims to modulate signaling pathways or correct underlying genetic defects.

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