Ciliopathies

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Children with the molar tooth sign on cerebral imaging and variable organ involvement
• Fetuses with hyperechogenic or cystic kidneys alongside skeletal or brain abnormalities
• Children with overlapping skeletal ciliopathy features, such as or
• Patients with early-onset obesity, polydactyly and rod-cone dystrophy suggesting
• Children with kidney failure of unknown cause, where is a frequent hereditary cause
• Young patients presenting with early-onset or alongside chronic kidney disease, particularly early-onset end-stage disease
• Patients with progressive lung disease, chronic rhinosinusitis and repeated middle ear infections
• Patients with laterality defects, subfertility or neonatal respiratory distress

Testing is most informative when a multisystem picture points to ciliary dysfunction but overlapping features do not identify the entity. In Joubert syndrome, gene-phenotype correlates guide surveillance: TMEM67 carries a higher risk of liver fibrosis, NPHP1, RPGRIP1L and TMEM237 renal involvement, CEP290 and AHI1 retinal dystrophy. In primary ciliary dyskinesia an early diagnosis is critical to reduce morbidity, yet there is no single gold standard confirmatory or exclusionary test, so genetics sits alongside nasal nitric oxide (nNO), high-speed video microscopy analysis, immunofluorescence, and transmission electron microscopy.

Each variant is classified according to criteria, and the report states the variant, its classification, and its clinical relevance for the referring clinician.

• Pathogenic or likely pathogenic variant: establishes a definitive molecular diagnosis, identifying the specific causative cilia gene and underlying condition to guide clinical management and surveillance.
• Variant of uncertain significance (VUS): yields an inconclusive result where current scientific evidence is insufficient to confirm or rule out pathogenicity. Periodic bioinformatic reanalysis (typically every 1–3 years) is recommended as diagnostic evidence accumulates.
• No pathogenic variant detected (negative result): does not fully exclude a genetic ciliopathy, as the causative variant may reside in an unlinked gene, a deep intronic region, or a regulatory sequence not captured by standard panel assays. Diagnostic escalation to panels with broader scope or whole genome sequencing (WGS) can be considered.
• Secondary or incidental findings: actionable secondary findings or carrier status for unrelated autosomal recessive conditions may be reported according to standard ACMG guidelines and patient consent.

After testing, the treating clinician may consider follow-up aligned with specialty-society guidelines, and expanded testing or reanalysis as evidence evolves. A confirmed germline variant carries familial implications, and testing can be offered to at-risk relatives. A variant of uncertain significance warrants cautious interpretation. Genetic counselling supports each of these considerations.

is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country. Please to check out access in your region.

Testing uses based multi-gene panels together with copy-number analysis, which detects the whole-gene deletions that occur in this group.