Ai Peng Tan1, Wui Khean Chong2. 1. National University Health System, 1E Kent Ridge Rd, Singapore, 119228, Singapore. ai_peng_tan@nuhs.edu.sg. 2. Great Ormond Street Hospital NHS Foundation Trust, Great Ormond St, London, WC1N 3JH, UK.
Abstract
BACKGROUND: Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis, midfacial hypoplasia, and syndactyly/symphalangism are features of this syndrome. Sturge-Weber syndrome (SWS) on the other hand is a congenital neurocutaneous disorder characterized by facial port-wine stains (PWSs) and leptomeningeal vascular capillary malformations. In 2013, the causative mutation underlying SWS (p.R183Q somatic activating mutation in the guanine nucleotide-binding protein alpha-q (GNAQ) gene) was identified. This mutation increases downstream signaling along the RAS/MAPK pathway, resulting in increased cell proliferation. The interaction between FGFR and the RAS/MAPK signaling pathway was proposed in recent years. Elevated synthesis of fibronectin in the calvaria of patients with Apert syndrome and increased fibronectin gene expression in port wine-derived fibroblasts of patients with Sturge-Weber disease have also been reported. CASE PRESENTATION: We report a unique case of Apert and Sturge-Weber syndromes occurring in the same patient. The child was noted to demonstrate features suggestive of Apert syndrome at birth, including brachycephaly, midface hypoplasia, and syndactyly. In addition, a left-sided facial port wine stain in the forehead was noted. Magnetic resonance imaging (MRI) of the brain was performed and confirmed the diagnosis of Sturge-Weber syndrome by demonstrating the presence of left sided leptomeningeal vascular capillary malformation and left-sided cerebral hemiatrophy. CONCLUSION: To the best of our knowledge, there has been no prior described case of Apert and Sturge-Weber syndromes occurring in the same patient. This case report identifies an area of potential research on fibronectin and derangement of the RAS/MAPK signaling pathway in relation to Apert syndrome and Sturge-Weber syndrome. In view of the rare concurrence of Apert and Sturge-Weber syndromes, the underlying pathogenesis is thought to be multifactorial, one of which may be related to either increased fibronectin gene expression or derangement of the RAS/MAPK signaling pathway.
BACKGROUND:Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis, midfacial hypoplasia, and syndactyly/symphalangism are features of this syndrome. Sturge-Weber syndrome (SWS) on the other hand is a congenital neurocutaneous disorder characterized by facial port-wine stains (PWSs) and leptomeningeal vascular capillary malformations. In 2013, the causative mutation underlying SWS (p.R183Q somatic activating mutation in the guanine nucleotide-binding protein alpha-q (GNAQ) gene) was identified. This mutation increases downstream signaling along the RAS/MAPK pathway, resulting in increased cell proliferation. The interaction between FGFR and the RAS/MAPK signaling pathway was proposed in recent years. Elevated synthesis of fibronectin in the calvaria of patients with Apert syndrome and increased fibronectin gene expression in port wine-derived fibroblasts of patients with Sturge-Weber disease have also been reported. CASE PRESENTATION: We report a unique case of Apert and Sturge-Weber syndromes occurring in the same patient. The child was noted to demonstrate features suggestive of Apert syndrome at birth, including brachycephaly, midface hypoplasia, and syndactyly. In addition, a left-sided facial port wine stain in the forehead was noted. Magnetic resonance imaging (MRI) of the brain was performed and confirmed the diagnosis of Sturge-Weber syndrome by demonstrating the presence of left sided leptomeningeal vascular capillary malformation and left-sided cerebral hemiatrophy. CONCLUSION: To the best of our knowledge, there has been no prior described case of Apert and Sturge-Weber syndromes occurring in the same patient. This case report identifies an area of potential research on fibronectin and derangement of the RAS/MAPK signaling pathway in relation to Apert syndrome and Sturge-Weber syndrome. In view of the rare concurrence of Apert and Sturge-Weber syndromes, the underlying pathogenesis is thought to be multifactorial, one of which may be related to either increased fibronectin gene expression or derangement of the RAS/MAPK signaling pathway.
Authors: Matthew D Shirley; Hao Tang; Carol J Gallione; Joseph D Baugher; Laurence P Frelin; Bernard Cohen; Paula E North; Douglas A Marchuk; Anne M Comi; Jonathan Pevsner Journal: N Engl J Med Date: 2013-05-08 Impact factor: 91.245
Authors: Qin Zhou; Jia Wei Zheng; Xiu Juan Yang; Yan An Wang; Wei Min Ye; Han Guang Zhu; Zhi Yuan Zhang Journal: Med Hypotheses Date: 2009-04-08 Impact factor: 1.538
Authors: Yonit A Addissie; Udhaya Kotecha; Rachel A Hart; Ariel F Martinez; Paul Kruszka; Maximilian Muenke Journal: Am J Med Genet A Date: 2015-08-06 Impact factor: 2.802