Table 2.

Disorders to Consider in the Differential Diagnosis of Apparent Nonsyndromic Tooth Agenesis

GeneDisorderMOIDental PhenotypeOther Features
Selected allelic disorders (i.e., disorders assoc w/genes also known to be involved in nonsyndromic tooth agenesis)
AXIN2 Oligodontia-colorectal cancer syndrome 1 (OMIM 608615)ADOligodontia (agenesis of molars, lower incisors & upper lateral incisors), odontomasOsteomas, colorectal cancer
EDA
EDAR
EDARADD 2		Hypohidrotic ectodermal dysplasia 3XL
AR
AD		Oligodontia, hypodontia, microdontia, anodontia, taurodontism, tooth malformationHypotrichosis, anhidrosis, hypohidrosis, possible mammary agenesis, frontal bossing, periorbital wrinkling & hyperpigmentation, depressed nasal bridge, prominent lips
FGFR1 Kallmann syndrome 4 (See Isolated Gonadotropin-Releasing Hormone Deficiency.)ADOligodontia, hypodontiaCleft lip/palate, anosmia, hypogonadism
IRF6 Van der Woude & popliteal pterygium syndromes (PPS) 5 (See IRF6-Related Disorders.)ADHypodontiaIn PPS, webbed skin of the legs, genital malformations, lip pits, orofacial clefts
MSX1 6Wiktop syndrome 7 (Witkop type ectodermal dysplasia 3) (OMIM 189500)ADOligodontia (2nd premolars & molars more affected), hypodontiaNail dysgenesis, orofacial clefts
WNT10A Odonto-onycho-dermal dysplasia 8 (OMIM 257980)AROligodontia, hypodontia, microdontiaSmooth tongue w/marked ↓ of fungiform & filiform papillae, keratoderma & hyperhidrosis of palms & soles, hyperkeratosis of the skin, onychodysplasia
Schöpf-Schulz-Passarge syndrome 9 (OMIM 224750)AROligodontia, hypodontia, microdontiaEyelid cysts, sparse & dry hair, dystrophic nails, dry skin, hyperkeratotic hand papules
Hypohidrotic ectodermal dysplasia 3AD
AR		Oligodontia, hypodontia, microdontia, anodontia, taurodontism, tooth malformationHypotrichosis, anhidrosis, hypohidrosis, possible mammary agenesis, frontal bossing, periorbital wrinkling & hyperpigmentation, depressed nasal bridge, prominent lips
Genes that preliminary research data suggest may also be assoc w/isolated nonsyndromic tooth agenesis (but insufficient data to state this definitively)
ANTXR1 Optic atrophy syndrome 10 (GAPO) (OMIM 230740)AROligodontia, hypodontia, failure of tooth eruption (pseudoanodontia)Delayed growth, alopecia, optic atrophy
COL17A1 11Junctional epidermolysis bullosa 12AROligodontia (no preferential tooth type missing), hypodontiaExtensive blistering, nail dystrophy, atrophic alopecia, amelogenesis imperfecta, dental caries
Genes assoc w/syndromic disorders involving ectodermal findings (Note: Listed disorders are limited to those w/o characteristic dysmorphic features &/or cognitive impairment.)
EVC
EVC2 		Weyers acrofacial dysostosis 13 (OMIM 193530)ADHypodontia, malocclusion, conical teeth, supernumerary teethMild short stature, postaxial polydactyly, dystrophic nails
FGF10 Lacrimoauriculodentodigital (LADD) syndrome 14 (OMIM 149730)ADHypodontia (maxillary incisors), microdontia, delayed eruption, enamel dysplasia, cariesDigital anomalies, hearing loss, lacrimal & salivary gland hypoplasia & aplasia, auricular anomalies
FGFR2 ADHypodontia, microdontia, agenesis of maxillary incisors, delayed eruption, enamel dysplasiaLacrimal duct aplasia, deafness, digital anomalies
GRHL2 Ectodermal dysplasia / short stature syndrome 16 (OMIM 616029)ARHypodontia, enamel hypoplasia, developmental delay of dentitionShort stature, nail dystrophy &/or loss, focal hyperkeratosis of hands & feet, hyperpigmentation of oral mucosa &/or tongue
KREMEN1 Ectodermal dysplasia, hair/tooth type 17 (OMIM 617392)AROligodontia, hypodontiaThin sparse hair, eyelashes & eyebrows, protruding lips, depressed nasal bridge, broad nose w/hypertelorism, down slanting palpebral fissures
LTBP3 18Dental anomalies & short stature (OMIM 601216) 19AROligodontia (no preferential tooth type missing), hypodontiaShort stature, mitral valve prolapse
OFD1 Oral-facial-digital syndrome type I 20XLHypodontia (lateral incisors), canine malpositionMicrognathia, lobulated tongue, tongue nodules, cleft lip/palate, accessory gingival frenula, hypoplastic alae nasi, syndactyly, polycystic kidney disease
PITX2 Axenfeld-Rieger syndrome, type 1 21 (OMIM 180500)ADOligodontia (upper lateral incisors & upper 2nd premolars), hypodontia, microdontia, enamel hypoplasiaEye anomalies, glaucoma, maxillary hypoplasia, umbilical anomalies
PVRL1 Cleft lip/palate-ectodermal dysplasia 22 (OMIM 225060)ARHypodontia, microdontiaCleft lip & palate, sparse scalp hair, syndactyly
TP63 Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3; orofacial cleft 8; Rapp-Hodgkin syndrome 23 (See TP63-Related Disorders.)ADHypodontia, microdontia, extensive dental caries, enamel hypoplasia, prominent marginal ridges of permanent maxillary incisors, round-shaped permanent molars, barrel-shaped permanent maxillary central incisorsCleft lip & palate, sparse/brittle/dry hair (trichodysplasia), ectodermal dysplasia, minor limb anomalies, tear duct anomalies, ankyloblepharon, nail abnormalities, T-cell lymphopenia
TSPEAR Ectodermal dysplasia 24 (OMIM 618180)ARHypodontia, microdontiaScalp hypotrichosis; skin, hair, & limb defects
1.
2.

Emerging evidence exists that mutation in this gene could cause isolated nonsyndromic tooth agenesis, but data are insufficient to state this definitively.

3.
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Larger deletions of the chromosome 4p16.2 region that include MSX1 and surrounding genes may lead to Wolf-Hirschhorn syndrome, depending on the deletion size and gene content. Individuals with Wolf-Hirschhorn syndrome can have hypodontia in addition to syndromic features including seizures, intellectual disability, muscular hypotonia, congenital heart defects, and cryptorchidism [Ozcan et al 2017].

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Mutation of this gene also leads to dystrophic epidermolysis bullosa (AD and AR) and epithelial recurrent erosion dystrophy (OMIM 122400; AD) but tooth agenesis is not a reported feature of these other phenotypes.

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Mutation of this gene also leads to geleophysic dysplasia (AD) but tooth agenesis is not a reported feature of this phenotype.

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From: Nonsyndromic Tooth Agenesis Overview

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