Table 2.
Gene | Patient number | Mutation (heterozygous unless stated otherwise) | Clinical features* | Bilateral | Family history | Number of limbs affected | Final diagnosis | Reference | ||
Hands | Feet | Other | ||||||||
GLI3 | OX1746 | 366C>G, Y122X | Synd 3rd web L | PrP, Synd 1st 2nd 3rd webs | Macrocephaly | Yes | Yes | 3 | GCPS | – |
GLI3 | OX2879 | 1320dupT, E441X | PrP, PoP type B | PrP, Synd 1st 2nd webs | Macrocephaly, undescended testicle | Yes | No | 4 | GCPS | 22 |
GLI3 | OX2877† | 2372delC, P791RfsX3 | PoP type B | – | – | Yes | Yes | 2 | PoP type A1 | 22 |
GLI3 | OX3536 | 2374C>T, R792X | PoP type B | PrP | Hypertelorism | Yes | Yes | 4 | GCPS | 22 |
GLI3 | OX3448 | Deletion exons 10–14 | PoP, Synd 2nd 3rd webs R hand, Synd 3rd 4th webs L hand | PrP, Synd 1st 2nd webs | – | Yes | Yes | 4 | GCPS | – |
HOXD13 | OX2137 | 165_185dup, A55_A61dup | Synd 3rd web | PoP, Synd 4th web | – | Yes | Yes | 4 | SPD1 | 18 |
HOXD13 | OX1928 | 752-2delA | Synd 3rd web R hand, clinodactyly little fingers | Extra bony element in 1st web space | – | Yes | Yes | 3 | SPD1 with foot anomaly | 23 |
HOXD13 | OX1749 | 940A>C, I314L | Lateral duplication of ring finger phalanges, Synd 3rd webs | – | – | Yes | Yes | 2 | SPD1/brachydactyly E overlap | 18 |
HOXD13 | OX1752 | 940A>C, I314L | Little finger hypoplasia, lateral duplication of ring finger phalanges | – | – | Yes | Yes | 2 | SPD1/brachydactyly E overlap | 18 |
HOXD13 | OX3015† | 955C>T, R319X | Clinodactyly little fingers | PoP | – | Yes | Yes | 3 | CLM with HOXD13 mutation | – |
SALL1 | OX3335§ | 995delC, P332HfsX10 | PrP, R side Wassel type 6, L side type 3 | – | Imperforate anus, rectal atresia, hypospadias, overfolded helices | Yes | No | 2 | Townes-Brocks syndrome | 22, 30 |
SALL1 | OX2948† | 3414_3415delAT, C1139WfsX14 | PrP R, TpT R | – | – | No | No | 1 | CLM with SALL1 mutation | 22 |
SALL4 | OX3701 | 2593C>T, R865X | Hypoplastic thumbs, L side Blauth type 3a, R side type 3b | – | Anal stenosis, ventriculo-septal defect, vascular malformation | Yes | Yes | 2 | Okihiro syndrome | – |
TBX5 | OX2084† | 266T>A, V89E | Grade 1 radial dysplasia with hypoplastic thumbs, Blauth type 4 R hand and type 5 L hand | – | – | Yes | No | 2 | Holt-Oram syndrome | – |
ZRS | OX1925 | 295T>C | TpT | – | – | Yes | No | 2 | TpT with ZRS mutation | 21 |
ZRS | OX3159 | 295T>C | TpT, PrP | – | – | Yes | Yes | 2 | PrP type II | 21 |
ZRS | OX3601 | 295T>C | TpT | – | – | Yes | Yes | 2 | TpT with ZRS mutation | 21 |
ZRS | OX3424 | Triplication | Complex polysyndactyly, fixed flexion at wrists | Complex polysyndactyly, severe talipes, mirror L foot | Closed spina bifida | Yes | No | 4 | Synd type IV (Haas) | – |
– | OX2612§ | t(2;18)(q14.2;p11.2) | Oligodactyly, more severe radially | Dislocated patellae, tibial shortening, fibular bowing, single digit | – | Yes | No | 4 | Split-hand/foot malformation with long bone deficiency 1 | 26 |
– | OX3689†‡ | dup(6)(p22.2p23) | PrP | – | Low birthweight, microcephaly, developmental delay | Yes | No | 2 | CLM with chromosome abnormality | – |
– | OX3084§ | del(22)(q11.2q11.2) | PrP | – | Cardiac malformation | No | No | 1 | 22q11.2 deletion syndrome | – |
– | OX3126§ | del(9)(p22.1) | Camptodactyly, thumb hypoplasia | – | – | Yes | No | 2 | 9p deletion syndrome | – |
ESCO2 | OX3470§ | Homozygous, 955+2_+5delTAAG | Radial dysplasia | Talipes equinovarus | Micrognathia, long columella, hypoplastic alae, nasal haemangioma, macrocephaly. | Yes | No | 2 | Roberts syndrome | 31 |
CLM, congenital limb malformation; GCPS, Greig cephalopolysyndactyly syndrome; L, left sided; PoP, postaxial polydactyly; PrP, preaxial polydactyly; R, right sided; Synd, syndactyly; SPD1, synpolydactyly 1; TpT, triphalangeal thumb.
*Limbs were bilaterally affected unless otherwise stated.
†Genetic abnormality that would not have been discovered by a clinically focused approach to mutation screening (see Discussion).
‡Cytogenetic diagnosis made as part of the study protocol.
§Clinical diagnosis made after consultation with clinical genetics service. Molecular genetic or cytogenetic diagnosis was made outside of this study.