A novel FGFR2 (S137W) mutation resulting in Apert syndrome

Abstract

Rationale: Apert syndrome (AS) is an autosomal dominant inheritance pattern of the most severe craniosynostosis syndrome. AS is characterized by synostosis of cranial sutures and acrocephaly, including brachycephaly, midfacial hypoplasia, and syndactyly of the hands and feet. Patients with AS often present with craniosynostosis, severe syndactyly, and skin, skeletal, brain, and visceral abnormalities. Patient concerns: A pregnant Chinese woman presented with a fetus at 23 + 5 weeks of gestation with suspected AS in a prenatal ultrasound examination. Following ultrasound, the pregnancy underwent spontaneous abortion. Gene sequencing was performed on the back skin of the dead fetus. Diagnosis: The diagnosis of AS was confirmed on the basis of clinical manifestations of the fetus, and a de novo mutation in the fibroblast growth factor receptor 2 ( FGFR2 ) gene was identified. Interventions: The couple finally chose to terminate the pregnancy based on the ultrasonic malformations and the risk of the parents having a neonate with AS in the future is small. However, any future pregnancy must be assessed by prenatal diagnosis. Outcomes: The dead fetus presented with bilateral skull deformation. Additionally, there were bilateral changes to the temporal bone caused by inwards movement leading to concave morphology, a “clover” sign, and syndactyly from the index finger/second toe to the little finger/little toe. AS was diagnosed by genetic testing, which showed a p.S137W (c.410C>G, chr10:123279677) mutation in the FGFR2 gene. Lessons: Clinicians should be aware that there are a variety of ultrasound findings for AS. Therefore, genetic testing should be used when appropriate to confirm diagnosis of AS.

Síndrome de Apert: Reporte de caso

“…El síndrome de Apert es un trastorno genético que se presenta de manera poco habitual y es caracterizado por una gran mutabilidad fenotípica, presentándose de forma típica en niños con macrocefalia y retraso en el desarrollo neurológico que son característicos de los pacientes con esta patología, Qingyang shi et al (26) , aluden que la mutación genética del FGFR2 se encuentra en más del 98% de los casos del SA denominadas P253R Y S252W, en este caso clínico describimos un paciente con SA que presenta desde la infancia distintas malformaciones óseas, rasgos faciales distintivos, confirmándose su diagnóstico con diferentes exámenes complementarios.…”

Cleft Palate in Apert Syndrome

“…Approximately 67% of Apert syndrome cases have the S252W variant, while P253R accounts for 32% of cases [ 15 , 16 , 17 ]. Other rare variants include Ser252Phe (S252F) [ 17 , 18 , 19 , 20 ], Ser137Trp (S137W) [ 21 ], Alu-element insertions in FGFR2 [ 22 ], and a deletion between FGFR2 exons IIIb and IIIc creating a chimeric IIIb/IIIc exon [ 23 ]. These are all gain-of-function FGFR2 mutations [ 24 , 25 ].…”