p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients

Abstract

C a s e R e p o r t e72 INTRODUCTIONApert syndrome (AS) is one of the most severe syndromic craniosynostosis syndromes.(1) It presents in utero with premature fusion of the cranial sutures (craniosynostosis) and severe symmetrical syndactyly of the hands and feet. Cerebral, cardiac, tracheal and genitourinary malformations may be present.Additional skeletal manifestations, acne lesions and intellectual disability are common.(2) AS has a reported prevalence of between 1:50,000 and 1:80,000, and the highest prevalence of AS has been reported in Asian populations.Over 300 cases have been reported since the syndrome was first described at the end of the 19th century.(4) AS shows autosomal dominant inheritance, but most cases are sporadic.It was established in 1995 that two mutations, p.Ser252Trp We report two patients with AS, in whom molecular analysis detected p.Ser252Trp and p.Pro253Arg mutations in the FGFR2 gene, respectively. This is the first report that details both clinically and molecularly diagnosed AS in Indonesia. CASE REPORTS Case 1Patient 1, a male baby born after an uneventful pregnancy to a healthy 34-year-old Javanese mother and a 35-year-old Javanese father, had no contributory family history. Delivery was byCaesarean section due to polyhydramnios at term, and the Apgar scores were 5, 7 and 8 at one, five and ten minutes, respectively. Birth weight was 3,300 g (50th centile), length was 50 cm (25th centile) and head circumference was 35 cm (25th centile). Physical examination at birth showed a brachycephalic skull, prominent forehead, midfacial hypoplasia, severe proptosis, downslanting palpebral fissures, low-set posteriorly rotated ears and high arched palate (Fig. 1). The anterior fontanel was 6 cm × 3 cm in diameter. The posterior fontanel was larger than the anterior fontanel, but the longest distance could not be measured due to the irregular shape. Widely spaced nipples, a systolic ejection murmur of grade III/6 and undescended testes were present. Bilateral, symmetrical cutaneous syndactyly, involving the second to fourth fingers, was present, and the thumbs were found to be broad. Both feet showed symmetrical cutaneous syndactyly of the first to fifth toes, as well as broad halluces.Cardiac ultrasonographic examination detected the presence of an atrial septal defect (ASD) that was 2 cm in diameter. Cerebral computed tomography revealed enlarged fontanels and a decreased anteroposterior diameter of the skull. The coronal and sagittal sutures were fused, but the lambdoid sutures were still patent. A clinical diagnosis of AS was made based on these findings. The patient died at 11 months of age due to severe pneumonia. Case 2Patient 2 was a three-month-old male baby born after an uneventful pregnancy to a healthy, nonconsanguineous 18-year-old ABSTRACT Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report...

Molecular analysis of exon 7 of the fibroblast growth factor receptor 2 (FGFR2) gene in an Indonesian patient with Apert syndrome: a case report

“…However, this frequent mutation is not generalized for all cases of AS since at least seven mutations in the FGFR2 gene have been found to cause AS [12, 13]. Subsequently, an advanced investigation of the whole gene is required with the aim of finding mutations that are possibly particular to the Indonesian population [17].…”

A novel FGFR2 (S137W) mutation resulting in Apert syndrome

“…However, in most developing countries, early intervention of AS is hampered by late diagnosis, a lack of facilities, and financial constraints. [ 10 ]…”

Apert syndrome with S252W FGFR2 mutation and characterization using Phenomizer: An Indian case report

“…13 Apart from the common mutation of FGFR2 at 252 and 253 position in exon IIIa; a case with 1372 bp deletion between exons IIIb and IIIc originating from recombination between 13 bp of identical DNA sequence present in both exons has also been reported.…”