Table 2.

Clinical characteristics of patients with a confirmed molecular genetic diagnosis

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.