1
(100.0%)

DHODH

Cleft upper lip Eyelid coloboma Hypoplasia of the ulna Micrognathia Short thumb

postaxial acrofacial dysostosis (OMIM) Postaxial acrofacial dysostosis (ORDO)

Autosomal recessive inheritance

1
(100.0%)

SEMA3E

Cleft upper lip Eyelid coloboma Hypoplasia of the ulna Micrognathia Short thumb

hypogonadotropic hypogonadism 7 with or without anosmia (OMIM) CHARGE syndrome (OMIM) CHARGE syndrome (ORDO)

Autosomal recessive inheritance Autosomal dominant inheritance Sporadic

1
(100.0%)

CHD7

Cleft upper lip Eyelid coloboma Hypoplasia of the ulna Micrognathia Short thumb

CHARGE syndrome (OMIM) hypogonadotropic hypogonadism 5 with or without anosmia (OMIM) CHARGE syndrome (ORDO) Omenn syndrome (ORDO) Normosmic congenital hypogonadotropic hypogonadism (ORDO) Kallmann syndrome (ORDO)

Autosomal dominant inheritance Sporadic Autosomal recessive inheritance

4
(98.7%)

ESCO2

Aplasia of the ulna Cleft upper lip Eyelid coloboma Micrognathia Short thumb

Roberts-SC phocomelia syndrome (OMIM) SC phocomelia syndrome (OMIM) Roberts syndrome (ORDO)

Autosomal recessive inheritance

5
(96.1%)

SF3B4

Aplasia/Hypoplasia of the ulna Cleft upper lip Hand oligodactyly Lower eyelid coloboma Microretrognathia

Nager acrofacial dysostosis (OMIM) Acrofacial dysostosis, Rodríguez type (ORDO) Nager syndrome (ORDO)

Autosomal dominant inheritance Autosomal recessive inheritance

6
(92.6%)

FGFR1

Cleft upper lip Eyelid coloboma Micrognathia Short metatarsal Shortening of all middle phalanges of the fingers

Pfeiffer syndrome (OMIM) Jackson-Weiss syndrome (OMIM) hypogonadotropic hypogonadism 2 with or without anosmia (OMIM) osteoglophonic dwarfism (OMIM) trigonocephaly 1 (OMIM) encephalocraniocutaneous lipomatosis (OMIM) Hartsfield-Bixler-Demyer syndrome (OMIM) Hartsfield syndrome (ORDO) Encephalocraniocutaneous lipomatosis (ORDO) Osteoglosphonic dysplasia (ORDO) Microform holoprosencephaly (ORDO) Septo-optic dysplasia spectrum (ORDO) Isolated trigonocephaly (ORDO) Normosmic congenital hypogonadotropic hypogonadism (ORDO) Kallmann syndrome (ORDO) Pfeiffer syndrome type 1 (ORDO) Oligodontia (ORDO)

Autosomal dominant inheritance Heterogeneous Somatic mosaicism Sporadic Autosomal recessive inheritance

7
(90.5%)

LRP4

Downslanted palpebral fissures Hypoplasia of the ulna Micrognathia Short finger Short philtrum

Cenani-Lenz syndactyly syndrome (OMIM) sclerosteosis 2 (OMIM) congenital myasthenic syndrome 17 (OMIM) Sclerosteosis (ORDO) Cenani-Lenz syndrome (ORDO) Postsynaptic congenital myasthenic syndromes (ORDO)

Autosomal recessive inheritance Autosomal dominant inheritance

7
(90.5%)

PDE4D

Epicanthus Hypoplasia of the ulna Micrognathia Short middle phalanx of finger Thin upper lip vermilion

acrodysostosis 2 with or without hormone resistance (OMIM) Acrodysostosis with multiple hormone resistance (ORDO) PDE4D haploinsufficiency syndrome (ORDO) Acrodysostosis (ORDO)

Autosomal dominant inheritance

7
(90.5%)

CHST3

Downslanted palpebral fissures Hypoplasia of the ulna Long philtrum Microretrognathia Short distal phalanx of finger

spondyloepiphyseal dysplasia with congenital joint dislocations (OMIM) Larsen-like syndrome, B3GAT3 type (OMIM) CHST3-related skeletal dysplasia (ORDO)

Autosomal recessive inheritance

7
(90.5%)

APC

Downslanted palpebral fissures Hypoplasia of the ulna Micrognathia Short thumb Thick upper lip vermilion

hepatocellular carcinoma (OMIM) desmoid tumor (OMIM) familial adenomatous polyposis 1 (OMIM) gastric cancer (OMIM) APC-related attenuated familial adenomatous polyposis (ORDO) Familial adenomatous polyposis due to 5q22.2 microdeletion (ORDO) Cenani-Lenz syndrome (ORDO) Gardner syndrome (ORDO) Desmoid tumor (ORDO) Turcot syndrome with polyposis (ORDO)

Heterogeneous Somatic mutation Autosomal dominant inheritance Autosomal recessive inheritance

7
(90.5%)

FGFR2

Epicanthus Hypoplasia of the ulna Long philtrum Micrognathia Shortening of all middle phalanges of the fingers

apert syndrome (OMIM) Saethre-Chotzen syndrome (OMIM) Pfeiffer syndrome (OMIM) Jackson-Weiss syndrome (OMIM) Crouzon syndrome (OMIM) Beare-Stevenson cutis gyrata syndrome (OMIM) LADD syndrome (OMIM) Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (OMIM) familial scaphocephaly syndrome, McGillivray type (OMIM) gastric cancer (OMIM) FGFR2-related bent bone dysplasia (OMIM) Jackson-Weiss syndrome (ORDO) Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome (ORDO) Familial scaphocephaly syndrome, McGillivray type (ORDO) Crouzon disease (ORDO) FGFR2-related bent bone dysplasia (ORDO) Saethre-Chotzen syndrome (ORDO) Antley-Bixler syndrome (ORDO) Apert syndrome (ORDO) Pfeiffer syndrome type 1 (ORDO) Pfeiffer syndrome type 2 (ORDO) Pfeiffer syndrome type 3 (ORDO)

Autosomal dominant inheritance Somatic mutation

12
(90.0%)

RIPK4

Absent thumb Eyelid coloboma Median cleft lip Micrognathia Short fifth metatarsal

CHAND syndrome (OMIM) Bartsocas-Papas syndrome (OMIM) Bartsocas-Papas syndrome (ORDO) CHAND syndrome (ORDO)

Autosomal recessive inheritance

13
(90.0%)

FLNB

Aplasia/Hypoplasia of the ulna Cleft upper lip Micrognathia Short distal phalanx of finger Telecanthus

atelosteogenesis type I (OMIM) atelosteogenesis type III (OMIM) Boomerang dysplasia (OMIM) Larsen syndrome (OMIM) spondylocarpotarsal synostosis syndrome (OMIM) Atelosteogenesis type I (ORDO) Boomerang dysplasia (ORDO) Larsen syndrome (ORDO) Atelosteogenesis type III (ORDO)

Autosomal dominant inheritance Sporadic Autosomal recessive inheritance

14
(89.8%)

CCNQ

Eyelid coloboma Hypoplasia of the radius Thin upper lip vermilion

syndactyly-telecanthus-anogenital and renal malformations syndrome (OMIM) Syndactyly-telecanthus-anogenital and renal malformations syndrome (ORDO)

X-linked dominant inheritance

15
(89.5%)

SALL4

Epicanthus Everted lower lip vermilion Hypoplasia of the ulna Micrognathia Short distal phalanx of the thumb

IVIC syndrome (OMIM) Duane-radial ray syndrome (OMIM) IVIC syndrome (ORDO) Duane retraction syndrome (ORDO) Acro-renal-ocular syndrome (ORDO)

Autosomal dominant inheritance

16
(89.4%)

SLC25A24

Micrognathia Short distal phalanx of finger Thin upper lip vermilion Upper eyelid coloboma

progeroid syndrome, Petty type (OMIM) Gorlin-Chaudhry-Moss syndrome (ORDO) Progeroid syndrome, Petty type (ORDO)

Autosomal dominant inheritance

17
(89.3%)

KRAS

Cleft upper lip Eyelid coloboma Micrognathia Radioulnar synostosis Short palm

arteriovenous malformations of the brain (OMIM) urinary bladder cancer (OMIM) hereditary breast carcinoma (OMIM) hereditary diffuse gastric adenocarcinoma (OMIM) linear nevus sebaceus syndrome (OMIM) lung cancer (OMIM) familial pancreatic carcinoma (OMIM) Toriello-Lacassie-Droste syndrome (OMIM) acute myeloid leukemia (OMIM) Noonan syndrome 3 (OMIM) autoimmune lymphoproliferative syndrome type 4 (OMIM) cardiofaciocutaneous syndrome 2 (OMIM) Familial pancreatic carcinoma (ORDO) Cardiofaciocutaneous syndrome (ORDO) Lynch syndrome (ORDO) Encephalocraniocutaneous lipomatosis (ORDO) Linear nevus sebaceus syndrome (ORDO) Toriello-Lacassie-Droste syndrome (ORDO) Noonan syndrome (ORDO)

Somatic mutation Autosomal dominant inheritance Somatic mosaicism Sporadic Autosomal recessive inheritance

18
(88.6%)

CUL7

Hypoplasia of the ulna Long philtrum Short 5th finger Short ribs Thick eyebrow

3M syndrome 1 (OMIM) 3M syndrome (ORDO)

Autosomal recessive inheritance Autosomal dominant inheritance

19
(88.1%)

RPS19

Cleft upper lip Epicanthus Hypoplasia of the radius Micrognathia Short thumb

Diamond-Blackfan anemia 1 (OMIM) Blackfan-Diamond anemia (ORDO)

Autosomal dominant inheritance

19
(88.1%)

NIPBL

Blepharitis Cleft upper lip Hypoplasia of the radius Micrognathia Short 1st metacarpal

Cornelia de Lange syndrome 1 (OMIM) Cornelia de Lange syndrome (ORDO)

Autosomal dominant inheritance Sporadic

21
(87.9%)

BRCA1

Aplasia/Hypoplasia of fingers Epicanthus Hypoplasia of the ulna Micrognathia Thick upper lip vermilion

hereditary breast carcinoma (OMIM) breast-ovarian cancer, familial, susceptibility to, 1 (OMIM) Fanconi anemia, complementation group S (OMIM) Familial pancreatic carcinoma (ORDO) Hereditary breast and ovarian cancer syndrome (ORDO) Primary peritoneal carcinoma (ORDO) Fanconi anemia (ORDO)

Autosomal dominant inheritance Somatic mutation Multifactorial inheritance Autosomal recessive inheritance

22
(87.9%)

DYNC2H1

Cleft upper lip Epicanthus Hypoplasia of the ulna Micrognathia Short palm

asphyxiating thoracic dystrophy 3 (OMIM) Jeune syndrome (ORDO) Short rib-polydactyly syndrome, Verma-Naumoff type (ORDO)

Autosomal recessive inheritance Digenic inheritanec

23
(87.7%)

TWIST1

Brachydactyly Micrognathia Radioulnar synostosis Short philtrum Upper eyelid coloboma

Saethre-Chotzen syndrome (OMIM) TWIST1-related craniosynostosis (OMIM) Robinow-Sorauf syndrome (OMIM) Sweeney-Cox syndrome (OMIM) Isolated scaphocephaly (ORDO) Isolated plagiocephaly (ORDO) Isolated brachycephaly (ORDO) Saethre-Chotzen syndrome (ORDO)

Autosomal dominant inheritance

24
(87.7%)

UBE2T

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group T (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

SLX4

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group P (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

BRIP1

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

hereditary breast carcinoma (OMIM) Fanconi anemia complementation group J (OMIM) Hereditary breast and ovarian cancer syndrome (ORDO) Fanconi anemia (ORDO)

Autosomal dominant inheritance Somatic mutation Autosomal recessive inheritance

24
(87.7%)

RAD51C

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group O (OMIM) breast-ovarian cancer, familial, susceptibility to, 3 (OMIM) Hereditary breast and ovarian cancer syndrome (ORDO) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

FANCC

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group C (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

FANCD2

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group D2 (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

FANCA

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group A (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

FANCE

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Fanconi anemia complementation group E (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

FANCI

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short 1st metacarpal

Fanconi anemia complementation group I (OMIM) Fanconi anemia (ORDO)

Autosomal recessive inheritance

24
(87.7%)

PALB2

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

hereditary breast carcinoma (OMIM) Fanconi anemia complementation group N (OMIM) Familial pancreatic carcinoma (ORDO) Hereditary breast and ovarian cancer syndrome (ORDO) Fanconi anemia (ORDO)

Autosomal dominant inheritance Somatic mutation Autosomal recessive inheritance

24
(87.7%)

BRCA2

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

hereditary breast carcinoma (OMIM) medulloblastoma (OMIM) familial prostate carcinoma (OMIM) Wilms tumor 1 (OMIM) Fanconi anemia complementation group D1 (OMIM) breast-ovarian cancer, familial, susceptibility to, 2 (OMIM) glioma susceptibility 3 (OMIM) pancreatic cancer, susceptibility to, 2 (OMIM) Familial pancreatic carcinoma (ORDO) Hereditary breast and ovarian cancer syndrome (ORDO) Nephroblastoma (ORDO) Fanconi anemia (ORDO)

Autosomal dominant inheritance Somatic mutation Autosomal recessive inheritance Heterogeneous Multifactorial inheritance

24
(87.7%)

RECQL4

Cleft palate Epicanthus Hypoplasia of the ulna Micrognathia Short thumb

Baller-Gerold syndrome (OMIM) rapadilino syndrome (OMIM) Rothmund-Thomson syndrome type 2 (OMIM) Baller-Gerold syndrome (ORDO) Rothmund-Thomson syndrome type 2 (ORDO)

Autosomal recessive inheritance

36
(87.7%)

FGFR3

Aplasia/Hypoplasia of the mandible Cleft palate Epicanthus Hypoplasia of the ulna Short middle phalanx of finger

achondroplasia (OMIM) urinary bladder cancer (OMIM) hypochondroplasia (OMIM) LADD syndrome (OMIM) nevus, epidermal (OMIM) thanatophoric dysplasia type 1 (OMIM) thanatophoric dysplasia type 2 (OMIM) testicular germ cell tumor (OMIM) Muenke syndrome (OMIM) cervical cancer (OMIM) camptodactyly-tall stature-scoliosis-hearing loss syndrome (OMIM) Crouzon syndrome-acanthosis nigricans syndrome (OMIM) severe achondroplasia-developmental delay-acanthosis nigricans syndrome (OMIM) Achondroplasia (ORDO) Thanatophoric dysplasia type 1 (ORDO) Isolated plagiocephaly (ORDO) Isolated brachycephaly (ORDO) Hypochondroplasia (ORDO) Muenke syndrome (ORDO) Saethre-Chotzen syndrome (ORDO) Camptodactyly-tall stature-scoliosis-hearing loss syndrome (ORDO) Severe achondroplasia-developmental delay-acanthosis nigricans syndrome (ORDO) Crouzon syndrome-acanthosis nigricans syndrome (ORDO) Thanatophoric dysplasia type 2 (ORDO)

Autosomal dominant inheritance Somatic mutation Somatic mosaicism Sporadic Autosomal recessive inheritance

37
(87.3%)

JAG1

Hypoplasia of the ulna Short distal phalanx of finger Thin vermilion border Upslanted palpebral fissure

Alagille syndrome due to a JAG1 point mutation (OMIM) tetralogy of fallot (OMIM) Tetralogy of Fallot (ORDO)

Autosomal dominant inheritance Multifactorial inheritance

38
(87.3%)

PSMD12

Downslanted palpebral fissures Micrognathia Short thumb Thin upper lip vermilion Upper limb undergrowth

Stankiewicz-Isidor syndrome (OMIM) 17q24.2 microdeletion syndrome (ORDO)

Autosomal dominant inheritance

38
(87.3%)

SLC26A2

Epicanthus Micrognathia Short middle phalanx of finger Thin upper lip vermilion Upper limb undergrowth

diastrophic dysplasia (OMIM) multiple epiphyseal dysplasia type 4 (OMIM) atelosteogenesis type II (OMIM) achondrogenesis type IB (OMIM) Atelosteogenesis type II (ORDO) Diastrophic dwarfism (ORDO) Achondrogenesis type 1B (ORDO) Multiple epiphyseal dysplasia type 4 (ORDO)

Autosomal recessive inheritance

40
(87.1%)

FRAS1

Aplasia/Hypoplasia of the sternum Aplasia/Hypoplasia of the thumb Cleft upper lip Upper eyelid coloboma

Fraser syndrome 1 (OMIM) Fraser syndrome (ORDO)

Autosomal recessive inheritance