Table 2

Summary details of patients with a positive genetic diagnosis

FamilySexGENEMutationInheritanceRefCRSClinical features†
3FCDC45c.[226A>C];[469C>T]p.[N76H];[R157C]Compound heterozygous32BCShort stature, thin eyebrows, anteriorly placed anus
4MIL11RAc.[886C>T];[886C>T]p.[R296W];[R296W]Homozygous22PExorbitism, intellectual disability, atopy. ?Crouzon syndrome
7FNovel‡HomozygousPMid-face hypoplasia, corneal ulceration, scoliosis, severe respiratory tract infections/bronchiectasis, mild–moderate developmental delay
9MIL11RAc.[98dupC];[98dupC]p.[G34fs*39];[G34fs*39]HomozygousS, BCCrouzonoid facies, mild developmental delay, dental anomalies, patent ductus arteriosus, atrial septal defect, umbilical hernia
1oMMSX2c.443C>Tp.P148LHeterozygous (from affected mother)33 34BCMild learning difficulties, short, broad thumbs, 5th finger clinodactyly, thick hair, squint and hydrocoele
11MFBN1c.8226+5G>ASpliceDe novo35S, MExorbitism, ligamentous laxity, recurrent inguinal herniae, tall stature; lens subluxation and mild aortic dilatation aged 8 years
14MHUWE1c.328C>Tp.R110WDe novo2MFacial dysmorphism, dental anomalies, pectus excavatum, scoliosis, long palms, Chiari malformation, moderate–severe intellectual disability
16MZIC1c.1101C>Ap.C367*Suspected de novo§S, BLMicrocephaly, asymmetric ventriculomegaly, possible abnormalities on MRI brain imaging
18MTWIST1c.350A>Tp.E117VDe novoMHypertelorism, wide anterior fontanelle, upper eyelid colobomas, pseudoproptosis, dysplastic cupped ears, syndactyly of fingers, bilateral talipes, bilateral undescended testes, imperforate anus, hypertrichosis
21FKRASc.40G>Ap.V14IDe novo36PExorbitism, cloverleaf skull
23F+MNovel¶Compound heterozygousBCBilateral superior vena cava, dilated cardiomyopathy, rudimentary right thumb, duplex kidney, anterior anus, bilateral inguinal herniae, growth deficiency
24FAHDC1c.2373_2374delTGp.C791fs*57De novo37BC, MModerate developmental delay, hoarse cry
29MSTAT3c.1915C>Tp.P639SDe novo39PCrouzonoid appearance, mild global developmental delay; necrotising pneumonia and bronchopleural fistula aged 3 years
37FNTRK2c.1330G>Tp.G444*Suspected de novo§LCFacial 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.