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Abstract：
Frank-ter Haar syndrome (FTHS) is a rare autosomal recessive syndrome resulting from mutations in the SH3PXD2B gene involved in the formation of podosomes and invadopodia which have a role in extracellular matrix remodelling and cell migration. FTHS is characterized by facial dysmorphism, megalocornea, inconstant glaucoma, variable developmental delay, skeletal and cardiac anomalies. To date, 40 patients have been reported in the literature with a clinical diagnosis of FTHS, only 20 patients having identified mutations. We present a review of these 20 reported patients and describe a patient born to non-consanguineous parents, with intrauterine growth retardation, hypotonia, congenital glaucoma, caudal appendix, scoliosis, camptodactyly, ventricular septal defect, thin corpus callosum and craniofacial features suggestive of FTHS. Clinical evolution resulted in buphthalmos worsening, coarsening of the facial features and respiratory failure leading to death at 4,5 months. Diagnosis was confirmed by the identification of a previously known homozygous mutation c.969delG, p.(Arg324Glyfs*19) in SH3PXD2B. This is the first description of very severe phenotype with lethal respiratory impairment in FTHS. Since very few patients are described in the literature, and 2 out of the 3 patients carrying the c.969delG mutation had a favourable clinical course, more cases are needed to better characterize the phenotype and understand the natural history of this syndrome. Furthermore, we hypothesize that the alteration of podosomes function could lead to a reduction of the extracellular matrix degradation and accumulation of the latter in the extracellular space, which might explain the coarsening of the facial features and the severe refractory glaucoma.
摘要：
Frank-terHaar综合征（FTHS）是一种罕见的常染色体隐性遗传综合征，是由SH3PXD2B基因突变引起的，该基因突变参与了在细胞外基质重塑和细胞迁移中的作用。FTHS的特点是面部畸形，巨角膜,不恒定的青光眼，可变发育延迟，骨骼和心脏异常。迄今为止,文献中报道了40例患者的临床诊断为FTHS，只有20名患者发现了突变。我们对这20例报告的患者进行了回顾，并描述了非近亲父母所生的患者，宫内发育迟缓，低张力,先天性青光眼,尾端阑尾,脊柱侧弯,Camptodactyly,室间隔缺损,薄的call体和颅面特征提示FTHS。临床演变导致Buthemos恶化，面部特征粗化和呼吸衰竭导致4,5个月时死亡。通过鉴定先前已知的纯合突变c.969delG来确认诊断，P.（Arg324Glyfs*19）在SH3PXD2B。这是FTHS中具有致死性呼吸损伤的非常严重表型的首次描述。由于文献中描述的患者很少，3例携带c.969delG突变的患者中有2例具有良好的临床病程，需要更多的病例来更好地表征表型并了解该综合征的自然史.此外，我们假设podosome功能的改变可能导致细胞外基质降解的减少和后者在细胞外空间的积累，这可能解释了面部特征的粗化和严重的难治性青光眼。
