Department of Pediatrics, Vittore Buzzi Children's Hospital, Department of Biomedical and Clinical Science L. Sacco, Università degli Studi di Milano, Milan, Italy.
Department of Pediatrics, Vittore Buzzi Children's Hospital, Università degli Studi di Milano, Milan, Italy.
Orphanet J Rare Dis. 2020 Apr 16;15(1):93. doi: 10.1186/s13023-020-01373-0.
Raine syndrome (RS) is a rare autosomal recessive disorder caused by biallelic loss-of-function mutations of FAM20C. The most common clinical features are microcephaly, exophthalmos, hypoplastic nose and severe midface hypoplasia, leading to choanal atresia. The radiological findings include generalized osteosclerosis and brain calcifications. RS is usually lethal during the neonatal period due to severe respiratory distress. However, there exists a non-lethal RS form, the phenotype of which is extremely heterogeneous. There is paucity of data about clinical course and life expectancy of these patients.
This is the first description of follow-up features of non-lethal RS patients. Moreover, we present three unpublished cases. There are five Asian and two Arab patients. All were born to consanguineous parents. The most common neonatal comorbidity was respiratory distress secondary to choanal atresia. A variable degree of neurodevelopmental delay was seen in the majority of our cases and seizures and hearing or vision involvement were also frequent. Neurological and orthopedic issues were the most frequent complications seen at follow-up in our group. Persistent hypophosphatemic rickets was the most striking endocrinological manifestation, which was scarcely responsive to therapy with phosphate salts and alfacalcidol. Life expectancy of our patients goes beyond childhood, with the oldest of those described being 18 years old at present.
Manifestations of RS in those surviving the neonatal period are being increasingly recognized. Our study supports previous findings and provides clinical and biochemical observations and data from longer follow up. Finally, we propose multidisciplinary follow up for patients with non-lethal RS.
Raine 综合征（RS）是一种罕见的常染色体隐性遗传病，由 FAM20C 的双等位基因功能丧失突变引起。最常见的临床特征是小头畸形、眼球突出、鼻发育不全和严重的中面部发育不全，导致后鼻孔闭锁。放射学表现包括全身性骨硬化和脑钙化。由于严重的呼吸窘迫，RS 通常在新生儿期致命。然而，存在一种非致死性 RS 形式，其表型极其异质。关于这些患者的临床过程和预期寿命的数据很少。
这是对非致死性 RS 患者随访特征的首次描述。此外，我们还介绍了三个未发表的病例。有五名亚洲人和两名阿拉伯人。所有患者均来自近亲结婚的父母。最常见的新生儿合并症是后鼻孔闭锁引起的呼吸窘迫。我们的大多数病例都存在不同程度的神经发育迟缓，癫痫发作和听力或视力损害也很常见。神经和骨科问题是我们组在随访中最常见的并发症。持续性低磷性佝偻病是最显著的内分泌表现，对磷酸盐盐和阿尔法骨化醇的治疗反应不佳。我们患者的预期寿命超过儿童期，目前描述的最年长的患者为 18 岁。
在新生儿期存活下来的 RS 患者的表现越来越被认识。我们的研究支持以前的发现，并提供了更长时间随访的临床和生化观察和数据。最后，我们建议对非致死性 RS 患者进行多学科随访。
