Table 1. Established ciliopathies and associated disease genes.
| Namea | Commonly observed clinical featuresb | Known disease gene(s)c |
|---|---|---|
| Acrocallosal syndrome (ACLS) | Agenesis of corpus callosum, distal anomalies of limbs, minor craniofacial anomalies and intellectual disability. | KIF7, GLI3 |
| Alström syndrome (ALMS) | Vision and hearing abnormalities, childhood obesity, cardiomyopathy. Later in life diabetes mellitus, liver and kidney dysfunction may develop. | ALMS1 |
| Bardet-Biedl syndrome (BBS) | Cone-rod dystrophy, polydactyly, truncal obesity, hypogonadism, kidney abnormalities, learning difficulties, congenital heart defects, cardiomyopathy. | ARL6, BBPIP1, BBS1, BBS2, BBS4, BBS5, BBS7, BBS9, BBS10, BBS12, C8ORF37, CEP290, IFT27, IFT74, IFT172, LZTFL1, MKKS, MKS1, SDCCAG8, TRIM32, TTC8, WDPCP |
| Carpenter syndrome (CRPT) | Craniosynostosis, skeletal and dental abnormalities, vision and hearing loss, congenital heart defects, genital abnormalities, obesity, intellectual disability. | MEGF8, RAB23 |
| Cerebellar vermis defect, oligophrenia, ataxia, coloboma, hepatic fibrosis (COACH) syndrome | Intellectual disability, liver fibrosis, ataxia, ocular anomalies (coloboma, nystagmus). Considered a rare form of Joubert syndrome. | CC2D2A, RPGRIP1L, TMEM67 |
| Cranioectodermal dysplasia (CED; also known as Sensenbrenner syndrome) | Skeletal and ectodermal defects, nephronophthisis, liver fibrosis, ocular anomalies (mainly retinitis pigmentosa), congenital heart defects | IFT43, IFT122, WDR19 (IFT144), WDR35 (IFT121) |
| Curry–Jones syndrome (CRJS) | Syndromic craniosynostosis, agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, skin and intestinal abnormalities, ocular anomalies (colobomas, microphthalmia), occipital meningoceles, intellectual disability, tumours (smooth muscle hamartomas, desmoplastic medulloblastoma). | SMO |
| Ellis–Van Creveld (EVC) syndrome | Short stature, short arms and legs, narrow chest with short ribs, polydactyly, missing and/or malformed nails, dental abnormalities, congenital heart defects. | EVC, EVC2 |
| Endocrine-cerebroosteodysplasia (ECO) | Various anomalies of the endocrine, cerebral, and skeletal systems, neonatal mortality. | CILK1 |
| Greig cephalopolysyndactyly syndrome (GCPS) | Polydactyly, syndactyly, ocular hypertelorism, macrocephaly, intellectual disability. | GLI3 |
| Holoprosencephaly (HPE) | Abnormal brain development, cyclopia, proboscis, intellectual disability, pituitary gland anomalies. | CDON, FGF8, FOXH1, GLI2, NODAL, PTCH1, SHH, SIX3, TGIF1, ZIC2 |
| Hydrolethalus syndrome (HLS) | Severe foetal malformations including craniofacial dysmorphic features and abnormalities of central nervous system, heart, respiratory tract and limbs. | HYLS1, KIF7 |
| Jeune asphyxiating thoracic dystrophy (JATD)/ (also known as shortrib thoracic dysplasia (SRTD)) | Defective bone development, including small chest and short ribs causing impaired growth and expansion of the lungs and breathing difficulties; shortened bones in the arms and legs, polydactyly, unusually shaped pelvic bones. | CEP120, DYNC2H1, DYNC2I1 (WDR60), DYNC2I2 (WDR34), DYNC2LI1, DYNLT2B, IFT43, IFT52, IFT80, IFT81, IFT140, IFT172, INTU, KIAA0586 (TALPID3), KIAA0753 (MNR), NEK1, TCTEX1D2, TTC21B (IFT139), WDR19 (IFT144), WDR35 (IFT121) |
| Joubert syndrome (JBTS) | Defective brain development, including absence or underdevelopment of the cerebellar vermis and a malformed brain stem, which cause the characteristic molar tooth sign on MRI. Congenital heart defects. Other symptoms include hypotonia, abnormal breathing patterns and eye movements, ataxia, distinctive facial features, and intellectual disability. | AHI1, ARL13B, ARL3, ARMC9, B9D1, B9D2, CC2D2A, CEP41, CEP104, CEP120, CEP290, CPLANE1, CSPP1, FAM149B1 213,214, IFT74, INPP5E, KATNIP 215,KIAA0586 (TALPID3), KIAA0753 (MNR), KIF7, MKS1, NPHP1, OFD1, PDE6D, PIBF1, RPGRIP1L, SUFU, TCTN1, TCTN2, TCTN3, TMEM67, TMEM107, TMEM138, TMEM216, TMEM218 216, TMEM231, TMEM237, TOGARAM1, TTC21B (IFT139), ZNF423 |
| Kallmann syndrome (KS: central hypogonadism) | Hypogonadotropic hypogonadism leading to impaired sexual development; impaired sense of smell. | >50 genes; see Ref. 217 |
| Leber congenital amaurosis (LCA) | Retinal defects, causing severe visual impairment beginning in infancy. Other symptoms include photophobia, nystagmus, keratoconus and extreme farsightedness. | AIPL1, ALMS1, CEP290, CNGA3 218, CRB1, CRX, DTHD1, GDF6, GUCY2D, IDH3A, IMPDH1, IQCB1 (NPHP5), KCNJ13, LCA5, LRAT, MYO7A, NMNAT1, PHPH2, RD3, RDH12, RPE65, RPGRIP1, SPATA7, TUBB4B, TULP1, USP45 |
| McKusick–Kaufman syndrome (MKKS) | Genitourinary malformations, postaxial polydactyly, congenital heart defects, choanal atresia, pituitary dysplasia, esophageal atresia and distal tracheoesophageal fistula, Hirschsprung disease, vertebral anomalies, and hydrops fetalis. Syndrome is allelic with Bardet-Biedl. | MKKS |
| Meckel syndrome (MKS) | Multiple kidney cysts, occipital encephalocele, polydactyly, congenital heart defects. Affected children may also display anomalies of head, face, liver, lungs, genitals, and urinary tract. | B9D1, B9D2, CC2D2A, CEP290, KIF14, MKS1, NPHP3, RPGRIP1L, TCTN2, TMEM67, TMEM107, TMEM216, TMEM231, TXNDC15 |
| Mental retardation, truncal obesity, retinal dystrophy, and micropenis syndrome (MORMS) | Intellectual disability, truncal obesity, retinal dystrophy, and micropenis in males. Cataracts may occur later in life. | INPP5E |
| Morbid obesity and spermatogenic failure (MOSPGF) | Morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure; intellectual disability, decreased sperm counts or azoospermia. | CEP19 |
| Nephronophthisis (NPHP) | Renal dysfunction, chronic tubulointerstitial nephritis, renal cyst formation and progression to end stage renal disease. Congenital heart defects, cardiomyopathy. | ANKS6, CEP83, CEP164, CEP290, DCDC2, GLIS2, IFT172, INVS, IQCB1, MAPKBP1 219, NEK8, NPHP1, NPHP3, NPHP4, RPGRIP1L, SDCCAG8, TMEM67, TTC21B (IFT139), WDR19 (IFT144), ZNF423 |
| Oculocerebrorenal syndrome of Lowe (OCRL) | Defects in eyes, central nervous system and kidneys; hypotonia and feeding difficulties, developmental delay, intellectual disability, behavioural problems, seizures and short stature. Occurs almost exclusively in males. | OCRL |
| Oral-facial-digital syndrome (OFDS) | Defective development of brain, heart, face, limbs and kidneys; polycystic kidneys. | C2CD3, C5orf42, CPLANE1, DDX59, IFT57, INTU, KIAA0753 (MNR), NEK1, OFD1, SCLT1, SCNM1, TBC1D32, TCTN3, TMEM107, TMEM138, TMEM216, TMEM231, WDPCP |
| Pallister-Hall syndrome (PHS) | Polydactyly, syndactyly, hypothalamic hamartoma, and bifid epiglottis. Other symptoms include imperforate anus, abnormalities in the kidneys, cardiac defects, small genitalia, lack of fingers, nail problems, cleft palate, bifid uvula, and development delay and behavioural problems. | GLI3 |
| Pituitary stalk interruption syndrome (PSIS) | Congenital abnormality of the pituitary leading to pituitary deficiency. | CDON, IFT56 (TTC26) 220, GPR161, HESX1, LHX4, PROKR2, ROBO1, WDR11 |
| Polycystic kidney/liver disease (PKD) | Enlarged cystic and dysfunctional kidneys and/or livers. | ALG5, ALG8, DNAJB11, DZIP1L, GANAB, JAG1, LRP5, PKD1, PKD2, PKHD1, PRKCSH, SEC63, |
| Retinitis pigmentosa (RP) | Retinal defects leading to progressive vision loss. | >90 genes; see RetNet, the Retinal Information Network |
| RHYNS syndrome | Syndromic retinal disorder characterized by the association of retinitis pigmentosa, hypopituitarism, nephronophthisis, and skeletal dysplasia. | TMEM67 221 |
| Senior–Løken syndrome (SLSN) | Nephronophthisis (NPHP) associated with retinal dystrophy. | CEP164, CEP290, INV, IQCB1, NPHP1, NPHP3, NPHP4, SDCCAG8, TRAF3IP1, WDR19 (IFT144) |
| Stromme syndrome (STROMS) | Usually characterized by microcephaly, ocular anomalies, and apple-peel intestinal atresia. Other symptoms include facial dysmorphism, motor delay and intellectual disability, as well as heart, brain, kidney, and craniofacial abnormalities. | CENPF |
| Syndactyly-telecanthus-anogenital and renal malformations (STAR) syndrome | Syndactyly, telecanthus, anogenital and renal malformations. | CCNQ 222 |
| Usher (USH) syndrome | Sensorineural hearing loss or deafness and progressive vision loss due to retinitis pigmentosa. | ADGRV1, ARSG, CDH23, CEP78d, CEP250, CIB2, CLRN1, DFNB31, ESPN, HARS1, MYO7A, PCDH15, PDZD7, USH1C, USH1G, USH2A, WHRN |
| Von Hippel-Lindau (VHL) disease | Abnormal growth of both benign and cancerous tumours and cysts in many parts of the body, including central nervous system, kidney, pancreas, adrenal glands and endolymphatic sac. Anxiety disorders. | VHL |
| Weyer acrodental dysostosis (WAD) | Milder form of Ellis-Van Creveld syndrome without congenital heart defects. | EVC, EVC2 |
a
The list of ciliopathy disease genes was modified from Ref.7.
b
Adapted from Genetic and Rare Diseases Information Center (GARD) and Orphanet.
c
Unless otherwise indicated, the genes listed were obtained by searching Ref.7 and the OMIM database using the disease name as search entry. Genes indicated in bold encode proteins localizing to the cilium–centrosome axis according to the SYSCILIA gold standard version 2 223, or alternative studies as indicated for some genes, where supporting references are indicated.
d
Studies have suggested that patients with CEP78 mutations can present with atypical Usher syndrome or retinitis pigmentosa 224.