Table 2

Summary details of patients with a positive genetic diagnosis

Family	Sex	GENE	Mutation		Inheritance	Ref	CRS	Clinical features†
3	F	CDC45	c.[226A>C];[469C>T]	p.[N76H];[R157C]	Compound heterozygous	32	BC	Short stature, thin eyebrows, anteriorly placed anus
4	M	IL11RA	c.[886C>T];[886C>T]	p.[R296W];[R296W]	Homozygous	22	P	Exorbitism, intellectual disability, atopy. ?Crouzon syndrome
7	F	Novel‡			Homozygous		P	Mid-face hypoplasia, corneal ulceration, scoliosis, severe respiratory tract infections/bronchiectasis, mild–moderate developmental delay
9	M	IL11RA	c.[98dupC];[98dupC]	p.[G34fs39];[G34fs39]	Homozygous	–	S, BC	Crouzonoid facies, mild developmental delay, dental anomalies, patent ductus arteriosus, atrial septal defect, umbilical hernia
1o	M	MSX2	c.443C>T	p.P148L	Heterozygous (from affected mother)	33 34	BC	Mild learning difficulties, short, broad thumbs, 5th finger clinodactyly, thick hair, squint and hydrocoele
11	M	FBN1	c.8226+5G>A	Splice	De novo	35	S, M	Exorbitism, ligamentous laxity, recurrent inguinal herniae, tall stature; lens subluxation and mild aortic dilatation aged 8 years
14	M	HUWE1	c.328C>T	p.R110W	De novo	2	M	Facial dysmorphism, dental anomalies, pectus excavatum, scoliosis, long palms, Chiari malformation, moderate–severe intellectual disability
16	M	ZIC1	c.1101C>A	p.C367*	Suspected de novo§	–	S, BL	Microcephaly, asymmetric ventriculomegaly, possible abnormalities on MRI brain imaging
18	M	TWIST1	c.350A>T	p.E117V	De novo	–	M	Hypertelorism, wide anterior fontanelle, upper eyelid colobomas, pseudoproptosis, dysplastic cupped ears, syndactyly of fingers, bilateral talipes, bilateral undescended testes, imperforate anus, hypertrichosis
21	F	KRAS	c.40G>A	p.V14I	De novo	36	P	Exorbitism, cloverleaf skull
23	F+M	Novel¶			Compound heterozygous		BC	Bilateral superior vena cava, dilated cardiomyopathy, rudimentary right thumb, duplex kidney, anterior anus, bilateral inguinal herniae, growth deficiency
24	F	AHDC1	c.2373_2374delTG	p.C791fs*57	De novo	37	BC, M	Moderate developmental delay, hoarse cry
25	F	EFNB1	c.325C>T	p.R109C	Paternal	38	RC	Hypertelorism
29	M	STAT3	c.1915C>T	p.P639S	De novo	39	P	Crouzonoid appearance, mild global developmental delay; necrotising pneumonia and bronchopleural fistula aged 3 years
37	F	NTRK2	c.1330G>T	p.G444*	Suspected de novo§	–	LC	Facial asymmetry, progressive onset of aggressive outbursts, ritualised behaviours and language delay, hyperphagic obesity, streak ovaries

†See online supplementary table S1 for detailed information.
‡Gene identity confirmed by functional testing (manuscript submitted).
§Father's sample not available for analysis.
¶Gene identity supported by similar case found on GeneMatcher; functional testing ongoing.
CRS, sutures fused in craniosynostosis: BC, bicoronal; BL, bilambdoid; LC, left coronal; LL, left lambdoid; M, metopic; P, pansynostosis; RC, right coronal; RL, right lambdoid; S, sagittal.