Clinical and genetic characteristics of craniosynostosis in Hungary

Abstract

Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied. Classification was based on the suture(s) involved and the associated clinical features. In syndromic cases, genetic analyses, including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3, and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The majority (88%) of all patients with craniosynostosis were nonsyndromic. The sagittal suture was most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Male, twin gestation, and very low birth weight were risk factors for craniosynostosis. Syndromic craniosynostosis was detected in 24 patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre-Chotzen syndromes were identified. In one patient, multiple-suture craniosynostosis was associated with achondroplasia. Clinical signs were not typical for any particular syndrome in six patients. Genetic abnormalities were detected in 18 syndromic patients and in 8 relatives. In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome. Our results indicate that detailed clinical assessment is of paramount importance in the classification of patients and allows indication of targeted molecular testing with the highest possible diagnostic yield.

Craniosynostosis: To study the spectrum and outcome of surgical intervention at a tertiary referral institute in India

“…The incidence of syndromic craniosynostosis was 9.2% in Sloan et al ’s[ 8 ] study, 20.5% in Oliveira et al ’s[ 9 ] study, 6% in Zakhary et al ’s [ 10 ] study, 12% in Bessenyei et al ’s[ 11 ] study, and 11.67% in our study.…”

“…[ 9 ] Zakhary et al [ 10 ] in his paper observed that there were 73% men and 27% women. Bessenyei et al [ 11 ] in his paper observed that the sagittal suture was the most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Kolar et al [ 12 ] in his paper noted a much higher incidence of metopic synostosis than has been reported in the traditional clinical literature.…”

<p>Prenatal Diagnosis of Pfeiffer Syndrome Patient with FGFR2 C.940-1G>C Variant: A Case Report</p>

“…2 We present the clinical findings of a patient with SP diagnosed inutero due to a variant in FRFR2 gene. [8][9][10][11][12][13] Although most cases are diagnosed in their neonatal stage, prenatal diagnosis is possible. Three-dimensional obstetric ultrasound is the first-line diagnostic tool for suspected PS, being useful to verify suture closure in the third trimester of pregnancy for the most severe cases 14 although the diagnosis with lower gestational ages has been reported.…”

A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations

“…This targeted approach identifies a causative variant in approximately 71-75% of probands with syndromic craniosynostosis, but rarely in those with nonsyndromic unisutural craniosynostosis. 1,5,6 Additional genes have been identified more recently, associated with a range of autosomal dominant, autosomal recessive, and X-linked craniosynostoses; most notably, TCF12 (coronal), ERF (sagittal, lambdoid), FREM1 (metopic), and EFNA4 (coronal). 3,[7][8][9] The relative causative contributions of these genes in a clinically ascertained cohort from a multidisciplinary craniofacial clinic is unclear.…”