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.[G34fs*39];[G34fs*39] | 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.