IllnessPoly-/syndactyly, pre- + postaxial; differential diagnosis

NGS +

Polydactyly and syndactyly are quite common clinically heterogeneous and often inherited malformations. Non-syndromic syndactyly occurs in numerous (sub)forms and varies even within one family. The phenotype of the individual patient is unilateral or bilateral, symmetric or asymmetric, complete or incomplete, cutaneous or bony. Several different bones may be involved, and the phenotype may vary between limbs. Polydactyly is also phenotypically variable in terms of the limb(s) affected and severity. Polydactyly is often divided into three main phenotypes: preaxial, central, and postaxial. Preaxial polydactyly usually involves the thumb and can manifest in several subtypes. Central polydactyly is associated with syndactyly and hand splits. Postaxial polydactyly is often bilateral and characterized by a hypoplastic or fully developed little finger, may be simple or complex in form, and is often associated with foot deformities. Syndromal forms should be differentiated prior to molecular genetic studies. These include several hundred different syndromes such as acrocephalosyndactyly in Apert, Carpenter, Pfeiffer and Saethre-Chotzen syndromes, Bardet-Biedl syndrome, short rib polydactyly including Jeune, Ellis-van-Creveld syndrome but also Smith-Lemli-Opitz syndrome as well as trisomy 13 and many others. Non-syndromic poly-/syndactyly is transmitted in all classical inheritance patterns but also caused multifactorially. The DNA-diagnostic yield is incomplete and depends also strongly on the phenotype.

References: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232527/

doi: 10.1097/GOX.0000000000001549

• Alias: Polydaktylie
• Alias: Polysyndaktylie
• Alias: Syndaktylie
• Alias: Synpolydaktylie
• Allelic: Acheiropody (LMBR1)
• Allelic: Aortic valve disease 1 (NOTCH1)
• Allelic: Aplasia of lacrimal + salivary glands (FGF10)
• Allelic: Atrioventricular septal defect 3 (GJA1)
• Allelic: Bardet-Biedl syndrome 15 (WDPCP)
• Allelic: Brachydactyly, type D (HOXD13)
• Allelic: Brachydactyly, type E (HOXD13)
• Allelic: Brachydactyly-syndactyly syndrome (HOXD13)
• Allelic: Cardioacrofacial dysplasia 2 (PRKACB)
• Allelic: Cenani-Lenz syndactyly syndrome (LRP4)
• Allelic: Chondrodysplasia punctata, XLD (EBP)
• Allelic: Craniometaphyseal dysplasia, AR (GJA1)
• Allelic: Craniosynostosis, nonspecific (FGFR2)
• Allelic: Cryptophthalmos, unilateral or bilateral, isolated (FREM2)
• Allelic: Curry-Jones syndrome, somatic mosaic (SMO)
• Allelic: Cutis laxa, AR, type IIE (LTBP1)
• Allelic: Erythrokeratodermia variabilis et progressiva 3 (GJA1)
• Allelic: Greig cephalopolysyndactyly syndrome (GLI3)
• Allelic: Holoprosencephaly 3 (SHH)
• Allelic: Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Allelic: Hypoplastic left heart syndrome 1 (GJA1)
• Allelic: Hypoplastic or aplastic tibia with polydactyly (LMBR1)
• Allelic: Laurin-Sandrow syndrome (LMBR1)
• Allelic: Leukemia, Philadelphia chromosome-positive, resistant to imatinib (ABL1)
• Allelic: Liebenberg syndrome (PITX1)
• Allelic: Microphthalmia with coloboma 5 (SHH)
• Allelic: Myasthenic syndrome, congenital, 17 (LRP4)
• Allelic: Oculodentodigital dysplasia (GJA1)
• Allelic: Oculodentodigital dysplasia, AR (GJA1)
• Allelic: Osteoarthritis-5 (GDF5)
• Allelic: Pallister-Hall syndrome (GLI3)
• Allelic: Pallister-Hall-like syndrome (SMO)
• Allelic: Palmoplantar keratoderma with congenital alopecia (GJA1)
• Allelic: Pelger-Huet anomaly (LBR)
• Allelic: Retinitis pigmentosa 51 (TTC8)
• Allelic: Retinitis pigmentosa 55 (ARL6)
• Allelic: Schizencephaly (SHH)
• Allelic: Sclerosteosis 2 (LRP4)
• Allelic: Single median maxillary central incisor (SHH)
• Allelic: Trigonocephaly 1 (FGFR1)
• Allelic: Triphalangeal thumb, type I (LMBR1)
• Achondroplasia (FGFR3)
• Acrocapitofemoral dysplasia (IHH)
• Acromesomelic dysplasia 2A (GDF5)
• Acromesomelic dysplasia 2B (GDF5)
• Acromesomelic dysplasia 2C, Hunter-Thompson type (GDF5)
• Adams-Oliver syndrome 5 [scalp aplasia cutis cong., term. transverse limb defects] (NOTCH1)
• Adams-Oliver syndrome 5 [scalp aplasia cutis congenita, terminal transverse limb defects] (NOTCH1)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Apert syndrome (FGFR2)
• Au-Kline syndrome (HNRNPK)
• Bardet-Biedl syndrome 1, modifier of (ARL6)
• Bardet-Biedl syndrome 13 (MKS1)
• Bardet-Biedl syndrome 14, modifier of (TMEM67)
• Bardet-Biedl syndrome 19 (IFT27)
• Bardet-Biedl syndrome 19 (IFT43)
• Bardet-Biedl syndrome 3 (ARL6)
• Bardet-Biedl syndrome 6 (MKKS)
• Bardet-Biedl syndrome 8 (TTC8)
• Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Bent bone dysplasia syndrome (FGFR2)
• Brachydactyly, HP:0001156 Clinodactyly, HP:0030084 Syndactyly, HP:0001159 (LTBP1)
• Brachydactyly, type A1 (IHH)
• Brachydactyly, type A1, C (GDF5)
• Brachydactyly, type A2 (GDF5)
• Brachydactyly, type C (GDF5)
• Branchiooculofacial syndrome (TFAP2A)
• CATSHL [CAmptodactyly, Tall Stature + Hearing Loss] syndrome (FGFR3)
• COACH syndrome 1 (TMEM67)
• Camptosynpolydactyly, complex (BHLHA9)
• Carpenter syndrome 2 (MEGF8)
• Carpenter syndrome [Acrocephalopolysyndactyly type II] (RAB23)
• Char syndrome (TFAP2B)
• Clubfoot, congenital, with/_out deficiency of long bones and/or mirror-image polydactyly (PITX1)
• Congenital heart defects + skeletal malformations syndrome (ABL1)
• Congenital heart defects, hamartomas of tongue, polysyndactyly (WDPCP)
• Cowden syndrome 5 (PIK3CA)
• Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Craniosynostosis 1 (TWIST1)
• Crouzon syndrome (FGFR2)
• Crouzon syndrome with acanthosis nigricans (FGFR3)
• Culler-Jones syndrome (GLI2)
• Diarrhea 3, secretory sodium, congenital, syndromic (SPINT2)
• Filippi syndrome [syndactyly type I, microcephaly, MR] (CKAP2L)
• Focal dermal hypoplasia (PORCN)
• Fraser syndrome 1 (FRAS1)
• Fraser syndrome 2 (FREM2)
• Fraser syndrome 3 (GRIP1)
• Fuhrmann syndrome (WNT7A)
• Greenberg skeletal dysplasia (LBR)
• Guttmacher syndrome (HOXA13)
• Hand-foot-uterus syndrome (HOXA13)
• Hartsfield syndrome (FGFR1)
• Holoprosencephaly 9 (GLI2)
• Holt-Oram syndrome (TBX5)
• Hypochondroplasia (FGFR3)
• Intellectual developmental disorder, XL 99 (USP9X)
• Intellectual developmental disorder, XL 99, syndromic, female-restricted (USP9X)
• Jackson-Weiss syndrome (FGFR1)
• Jackson-Weiss syndrome (FGFR2)
• Joubert syndrome 22 (PDE6D)
• Joubert syndrome 28 (MKS1)
• Joubert syndrome 6 (TMEM67)
• Kaufman oculocerebrofacial syndrome (UBE3B)
• LADD [LacrimoAuriculoDentoDigital] syndrome (FGF10)
• LADD [LacrimoAuriculoDentoDigital] syndrome (FGFR2)
• LADD [LacrimoAuriculoDentoDigital] syndrome (FGFR3)
• MEND [Male Emopamil binding protein disturbance + Neurologic Defects {panelapp}] syndrome (EBP)
• McKusick-Kaufman syndrome (MKKS)
• Meckel syndrome 1 (MKS1)
• Meckel syndrome 3 (TMEM67)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (CCND2)
• Metacarpal 4-5 fusion (FGF16)
• Microphthalmia with limb anomalies (SMOC1)
• Microphthalmia, syndromic 6 (BMP4)
• Mirror-image polydactyly of hands and feet [panelapp] (MIPOL1)
• Muenke syndrome (FGFR3)
• Multinucleated neurons, anhydramnios, renal dysplasia, cereb. hypoplasia, hydranencephaly (CEP55)
• Multiple synostoses syndrome 2 (GDF5)
• Nephronophthisis 11 (TMEM67)
• Oligosyndactyly of the hands, Cenani-Linz-like (GREM1)
• Orofaciodigital syndrome V (DDX59)
• Osteoglophonic dysplasia (FGFR1)
• Patent ductus arteriosus 2 (TFAP2B)
• Pfeiffer syndrome
• Pfeiffer syndrome (FGFR1)
• Polydactyly [panelapp] (SHH)
• Polydactyly, postaxial, type A1 + type B (GLI3)
• Polydactyly, postaxial, type A10 (KIAA0825)
• Polydactyly, postaxial, type A6 (ZNF141)
• Polydactyly, postaxial, type A7 (IQCE)
• Polydactyly, postaxial, type A8 (GLI1)
• Polydactyly, postaxial, type A9 (FAM92A)
• Polydactyly, preaxial I (GLI1)
• Polydactyly, preaxial type II (LMBR1)
• Polydactyly, preaxial, type IV (GLI3)
• Postaxial foot polydactyly [panelapp] (PRKACB)
• Postaxial hand polydactyly [panelapp] (PRKACB)
• Postaxial polydactyly [MONDO:0020927] (SMO)
• Postaxial polydactyly type A9 [panelapp] (HAUS6)
• Preaxial polydactyly [panelapp] (SHH)
• RHYNS syndrome (TMEM67)
• Reynolds syndrome (LBR)
• Rhizomelic skeletal dysplasia with/-out Pelger-Huet anomaly (LBR)
• Robinow-Sorauf syndrome (TWIST1)
• SADDAN (FGFR3)
• Saethre-Chotzen syndrome (FGFR2)
• Saethre-Chotzen syndrome with/-out eyelid anomalies (TWIST1)
• Scaphocephaly + Axenfeld-Rieger anomaly (FGFR2)
• Scaphocephaly, maxillary retrusion + mental retardation (FGFR2)
• Short-rib thoracic dysplasia 8 with/-out polydactyly (DYNX2I1)
• Simpson-Golabi-Behmel syndrome, type 1 (GPC3)
• Stromme syndrome (CENPF)
• Sweeney-Cox syndrome (TWIST1)
• Symphalangism, proximal, 1B (GDF5)
• Syndactyly type 7 [panelapp] (LRP4)
• Syndactyly, mesoaxial synostotic, with phalangeal reduction (BHLHA9)
• Syndactyly, type III (GJA1)
• Syndactyly, type IV (LMBR1)
• Syndactyly, type V (HOXD13)
• Synpolydactyly 1 (HOXD13)
• Synpolydactyly [panelapp] (MAPKAPK5)
• Synpolydactyly, 3/3'4, associated with metacarpal + metatarsal synostoses (FBLN1)
• Thanatophoric dysplasia, type I, II (FGFR3)
• Townes-Brocks branchiootorenal-like syndrome (SALL1)
• Townes-Brocks syndrome 1 (SALL1)
• Triphalangeal thumb-polysyndactyly syndrome (LMBR1)
• Ulna and fibula, absence of, with severe limb deficiency (WNT7A)
• Ulnar-mammary syndrome (TBX3)