| Category | Item | Inheritance / role | Supported details | Example variants / detection notes | Example ontology terms | Evidence |
|---|---|---|---|---|---|---|
| Gene | **IFT122** | Autosomal recessive; IFT-A / retrograde intraflagellar transport | First CED gene identified; 13 patients from 12 families analyzed in the 2010 AJHG study; reduced frequency and length of primary cilia in patient fibroblasts; not all patients carried IFT122 variants, supporting genetic heterogeneity | Homozygous missense and compound heterozygous splice-site + missense genotypes reported; variants absent in 340 control chromosomes | GO:0030990 *intraciliary transport particle A*; GO:0005929 *cilium* | (pqac-00000004) |
| Gene | **WDR35 (IFT121)** | Autosomal recessive; IFT-A / retrograde intraflagellar transport | Independently identified by exome sequencing in two unrelated patients; CED described with craniosynostosis plus ectodermal and skeletal abnormalities; WDR35 defects underlie a subset of CED and can be associated with severe renal disease | c.25-2A>G (p.I9TfsX7), c.1877A>G (p.E626G), c.2891delC (p.P964Lfs*15), c.2623G>A (p.A875T); additional reported variants include c.2912A>G (p.Tyr971Cys), c.504T>A (p.Ser168Arg), c.1922T>G (p.Leu641*), c.2590C>T (p.Gln864*), c.2408_2416del (p.Asn803_Ala805del); RT-PCR used to confirm splicing effect in one study | GO:0030990 *intraciliary transport particle A*; GO:0005929 *cilium* | (pqac-00000001, pqac-00000003, pqac-00000006, pqac-00000009) |
| Gene | **IFT140** | Autosomal recessive; IFT-A / retrograde intraflagellar transport | Rare cause of CED; both 2020 and 2023 reports emphasize early-onset renal failure/ESRD in some patients; 2023 report states only four patients had previously been described with this cranioectodermal phenotype | c.326T>C (p.Leu109Pro), c.1565G>A (p.Gly522Glu), c.2767_2768+2del, and recurrent tandem duplication c.3454-488_4182+2588dup (p.Tyr1152_Thr1394dup); duplication may be missed by standard NGS and required coverage/CNV analysis plus qPCR, duplex or multiplex PCR, breakpoint Sanger sequencing, and in one case WGS | GO:0030990 *intraciliary transport particle A*; GO:0005929 *cilium* | (pqac-00000005, pqac-00000007, pqac-00000010, pqac-00000012, pqac-00000013) |
| Gene | **IFT43** | Autosomal recessive; gene listed among six established CED genes; IFT-related ciliopathy gene | Included in updated six-gene CED set in 2020 and 2023 sources; no specific patient-level variant examples were provided in the supplied snippets | No exemplar variant available in provided evidence snippets | GO:0005929 *cilium* | (pqac-00000007, pqac-00000009) |
| Gene | **WDR19** | Autosomal recessive; gene listed among six established CED genes; IFT-A complex member in 2013 summary | Included in updated six-gene CED set; cited among previously reported causal genes in 2013 Clinical Genetics summary | No exemplar variant available in provided evidence snippets | GO:0030990 *intraciliary transport particle A*; GO:0005929 *cilium* | (pqac-00000003, pqac-00000007, pqac-00000009) |
| Gene | **IFT52** | Autosomal recessive; gene listed among six established CED genes; IFT-related ciliopathy gene | Included in updated six-gene CED set in 2020 and 2023 sources | No exemplar variant available in provided evidence snippets | GO:0005929 *cilium* | (pqac-00000007, pqac-00000009) |
| Phenotype domain | **Craniofacial** | Congenital/early childhood; often recognizable clinically | Dolichocephaly, frontal bossing, low-set ears, sagittal craniosynostosis, brachycephaly, epicanthus, short neck; craniofacial pattern is a major diagnostic clue | Often prompts surgical/craniofacial evaluation; one IFT140 case underwent vault remodeling at 7 months | HP:0000268 *Dolichocephaly*; HP:0002007 *Frontal bossing*; HP:0006114 *Sagittal craniosynostosis*; HP:0000248 *Brachycephaly*; HP:0000286 *Epicanthus* | (pqac-00000003, pqac-00000007, pqac-00000009, pqac-00000010, pqac-00000013) |
| Phenotype domain | **Skeletal** | Congenital; variable severity | Narrow/small thorax or narrow chest, short-rib dysplasia, rhizomelic shortening or small limbs, shortening of long bones, brachydactyly, terminal hypoplasia of fingers, cone-shaped epiphyses, pectus excavatum | Skeletal findings overlap with other ciliopathies and support inclusion in skeletal dysplasia differential diagnosis | HP:0000774 *Narrow thorax*; HP:0008905 *Rhizomelia*; HP:0001156 *Brachydactyly*; HP:0003026 *Short rib*; HP:0010442 *Cone-shaped epiphyses*; HP:0000767 *Pectus excavatum* | (pqac-00000004, pqac-00000006, pqac-00000007, pqac-00000009, pqac-00000010, pqac-00000013) |
| Phenotype domain | **Ectodermal** | Early childhood; common and diagnostically useful | Sparse/thin hair, short/thin nails, nail dysplasia, abnormal/small teeth, dental anomalies, skin laxity | Dental and nail findings help distinguish CED from overlapping skeletal ciliopathies | HP:0008070 *Sparse hair*; HP:0008386 *Short nail*; HP:0002164 *Nail dysplasia*; HP:0006482 *Abnormality of dental morphology*; HP:0001597 *Skin laxity* | (pqac-00000004, pqac-00000007, pqac-00000009, pqac-00000013) |
| Phenotype domain | **Renal** | Often progressive in infancy/childhood; major prognostic driver | Nephronophthisis/CKD, chronic renal failure, tubulointerstitial nephritis, early-onset ESRD; ClinicalTrials.gov summary notes many patients develop CKD due to nephronophthisis typically between ages 2–6 years | Severe cases required dialysis, nephrectomy, pediatric kidney transplantation; urinary protein/creatinine ratio 4.32 mg/mmol and urinary microalbumin 595.0 mg/L reported in one 2023 WDR35 case | HP:0000090 *Nephronophthisis*; HP:0000112 *Chronic kidney disease*; HP:0003774 *Stage 5 chronic kidney disease* | (pqac-00000003, pqac-00000005, pqac-00000007, pqac-00000008, pqac-00000009, pqac-00000010, pqac-00000013) |
| Phenotype domain | **Hepatic** | Variable; may emerge with progression | Hepatic fibrosis, cystic liver disease, liver anomalies; hepatic and renal disease together broaden CED into a hepatorenal fibrocystic phenotype | Liver involvement is less uniformly described than renal disease but repeatedly noted in case summaries | HP:0001395 *Hepatic fibrosis*; HP:0001407 *Hepatic cysts* | (pqac-00000003, pqac-00000004, pqac-00000007, pqac-00000009) |
| Phenotype domain | **Ocular** | Variable | Retinal dystrophy/retinopathy, hyperopia, strabismus, nystagmus, optic nerve atrophy (reported as common in some IFT140-associated cases, though absent in one 2023 proband) | Ocular involvement is important for longitudinal surveillance because some patients lack eye findings early | HP:0000505 *Visual impairment*; HP:0000486 *Strabismus*; HP:0000639 *Nystagmus*; HP:0000580 *Hypermetropia*; HP:0000556 *Retinal dystrophy* | (pqac-00000005, pqac-00000008, pqac-00000009, pqac-00000012) |


*Table: This table condenses the evidence-supported genetic architecture and major clinical domains of cranioectodermal dysplasia (Sensenbrenner syndrome). It emphasizes the core IFT genes, representative variants, CNV/duplication detection pitfalls, and phenotype domains with example HPO terms for knowledge-base curation.*