Table 2 Clinical features observed in OFD syndromes
LOCUS | Inheritance | Oral features | Facial features | Hands anomalies | Feet anomalies | Skin/Hair features | Renal features | Cardiac features | Cerebral features | Skeletal features | Other abnormalities | Main references |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
OFD I | X-linked dominant (lethal in males) | Gingival frenulae Lingual hamartomas Cleft/lobulated tongue Cleft palate | Hypertelorism Cleft lip Pseudocleft of the upper lip | Brachydactyly Clinodactyly Polydactyly | Preaxial polydactyly | Miliae Alopecia | Polycystic kidney disease | – | Corpus callosum agenesis, cerebellar hypoplasia | – | Intellectual disability (50 %), cystic ovary and liver | |
OFD II | Autosomal recessive | Gingival frenulae Lingual hamartomas Cleft/lobulated tongue Cleft palate | – | Brachydactyly Clinodactyly Polydactyly | Broad hallux Pre/postaxial polydactyly | Thick hair | – | Rare | Porencephaly, Hydrocephaly | Median Y-shaped metacarpal | – | [3] |
OFD III | Autosomal recessive | Bifid uvula Lingual hamartomas Lobulated tongue Tooth hypoplasia | Hypertelorism Bulbous nose Low-set ears | Postaxial polydactyly | Postaxial polydactyly | – | End stage Renal failure I–II decade of life | – | Cerebellar vermis hypoplasia. DW malformation with cystic dilation of the IV ventricle. Myoclonia/Eye movement | – | Pectus excavatum Severe intellectual disability | |
OFD IV | Autosomal recessive | Gingival frenulae Lingual hamartomas Lobulated tongue Cleft palate | Epicanthus Micrognathia Low-set ears | Brachydactyly Clinodactyly Pre/postaxial polydactyly | Pre/postaxial polydactyly | – | Renal cysts | – | Porencephaly, Occipital encephalocele, Agenesis of corpus callosum, Vermis hypoplasia with MTS | Pectus excavatum Tibial abnormalities | Short stature, Variable intellectual disability | |
OFD V | Autosomal recessive | Gingival frenulae (rare) | Midline cleft lip | Postaxial polydactyly | Postaxial polydactyly | – | – | – | – | – |  | [3] |
OFD VI | Autosomal recessive | Gingival frenulae Lingual hamartomas Lobulated tongue Cleft palate | Hypertelorism Cleft lip | Brachydactyly Clinodactyly Syndactyly Median/Postaxial polydactyly | Broad hallux Preaxial polydactyly | – | Renal genesis Renal dysplasia | Rare | Vermis hypoplasia with MTS | Median Y-shaped metacarpal | Variable intellectual disability | |
OFD VII | X-linked dominant | Gingival frenulae Lingual hamartomas Cleft palate | Hypertelorism Cleft lip Asymmetry | Clinodactyly | – | – | Polycystic kidney disease | – | – | – | Moderate intellectual disability | [3] |
OFD VIII | X-linked recessive | Gingival frenulae Lingual hamartomas Lobulated tongue Epiglottis hypoplasia | Midline cleft lip Telecanthus Large nose | Bifid thumb Postaxial polydactyly | Preaxial polydactyly | – | – | – | – | Tibia and radius hypoplasia | Psychomotor delay Precocious lethality | [67] |
OFD IX | Autosomal recessive | Gingival frenulae Lingual hamartomas Lobulated tongue, Cleft palate | Midline cleft lip Synophrys | Brachydactyly Clinodactyly Polydactyly | Bifid toes | – | – | SD | – | – | Short stature, Microphthalmia, Coloboma | |
OFD X | Sporadic | Gingival frenulae Cleft palate | Telecanthus Flat nasal root Retrognathia | Oligodactyly Preaxial polydactyly | – | – | – | – | – | Short 4 limbs Bilateral short radius, Fibular agenesis | – | [69] |
OFD XI | Sporadic | Gingival frenulae Cleft palate | Hypertelorism Auricular pits Blepharophimosis | Postaxial polydactyly | Postaxial polydactyly | – | – | – | Ventricular dilatation | Odontoid hypoplasia, Vertebral abnormalities | Deafness, severe intellectual disability, behavioural troubles | [70] |
OFD XII | Sporadic | Gingival frenulae Bifid tongue Supernumerary teeth | Macrocephaly Hypertelorism | Pre/postaxial polydactyly | Preaxial polydactyly Club feet | – | – | Septum hypertrophy | Sylvius aqueduct stenosis, corpus callosum agenesis, vermis hypoplasia, myelomeningocele | Short tibiae, Central Y-shaped metacarpal | – | [71] |
OFD XIII | Sporadic | Lingual hamartomas | Cleft lip | Brachydactyly Clinodactyly Syndactyly | Brachydactyly Clinodactyly Syndactyly | – | – | Mitral and tricuspid valve dysplasia | Leucoaraïosis | – | Neuropsychiatric troubles, Epilepsy | [72] |
OFD XIV | Autosomal recessive | Gingival frenulae, Lingual hamartomas Cleft/lobulated tongue, Cleft palate | Telecanthus | Postaxial polydactyly | Duplication of hallux | – | – | – | Corpus callosum agenesis Vermis hypoplasia with MTS | – | Severe microcephaly Micropenis | [43] |
Unclassified OFD | Autosomal recessive | Lobulated tongue Cleft palate | Median cleft lip | Postaxial polydactyly | NA | Thick hair | Fused kidneys | TOF VSD | Corpus callosum agenesis | Â | Moderate intellectual disability. Hirschsprung disease | [47] |
Unclassified OFD | Autosomal recessive | Lingual hamartomas | – | Postaxial polydactyly | Duplication of hallux | – | – | Coarctation of the aorta | – | 5th Y-shaped metacarpal | – | [44] |