The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome...The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes.In this report,we studied a 9-year-old girl with CINCA.The eyes were also involved and presented bilateral papilledema.Genetic testing revealed that the symptoms were caused by a novel gene mutation site(c.913G>A,p.D305N)in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA.The patient had the characteristic facial features,frontal fossa and saddle nose,manifested the generalized urticaria-like skin rash at two weeks after birth,periodic fever 6 months after birth,sensorineural deafness at 7 years old,and bilateral papilledema,aseptic meningitis and knee arthropathy at 9 years old.White cell counts,C-reactive protein increased and intracranial pressure raised to 300 mmH2O.The meningeal thickening enhanced by gadolinium in magnetic resonance imaging(MRI).Based on clinical features and genetic test,the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms.With 3-year follow-up,patient had no inflammatory flare-up with visual acuity improvement.The finding of novel genetic mutation site(p.D305N)in NLRP3 gene expanded genotype spectrum associated with CINCA.This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.展开更多
目的探讨慢性婴儿神经、皮肤、关节综合征(CINCA)的基因突变、临床表型、治疗及预后情况,从而提高本病的诊断率、降低致残率和致畸率。方法回顾性分析本院诊断的10例CINCA综合征患儿的临床表型、辅助检查、治疗及随访情况。经家长同意...目的探讨慢性婴儿神经、皮肤、关节综合征(CINCA)的基因突变、临床表型、治疗及预后情况,从而提高本病的诊断率、降低致残率和致畸率。方法回顾性分析本院诊断的10例CINCA综合征患儿的临床表型、辅助检查、治疗及随访情况。经家长同意后取患儿及父母各3 ml EDTA抗凝血,用QIAamp全血DNA提取试剂盒(德国Qiagen公司)提取基因组DNA,应用Agilent液相捕获目标基因技术(Agilent公司)进行全外显子基因检测,最后应用Sanger测序法进行验证。结果本研究共发现CINCA综合征患儿NLRP3基因有8个杂合突变位点,分别是913G/A(D305N)、1057G/T(V353L)、1702T/A(F568I)、1703T/A(F568Y)、1710G/C(K570N)、1789A/G(S597G)、1991T/C(M664T)、2269G/A(G757R)。本病多数于生后半月起病,起病表现主要是荨麻疹样皮疹。10例患儿均可见身材矮小和特殊面容。所有患儿病程中均有不同程度发热和荨麻疹样皮疹,9例患儿有明显的关节炎,9例患儿有中枢神经系统受累的表现。8例患儿存在双耳神经性耳聋,7例患儿出现双眼视神经炎,6例患儿有肝脾和/或淋巴结肿大。淀粉样蛋白A明显升高。糖皮质激素和免疫抑制剂是治疗本病的基本用药,疗效不佳者需早期加用生物制剂缓解病情。结论CINCA综合征是一种罕见的常染色体显性遗传性疾病,以皮肤、关节和中枢神经系统受累为主要表现,可合并脏器淀粉样变性,早期诊断和治疗可以减少重要脏器受累。展开更多
文摘The rare disease of chronic infantile neurological cutaneous and articular(CINCA)syndrome,is caused by the over-secretion of interleukin(IL)-1βdue to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes.In this report,we studied a 9-year-old girl with CINCA.The eyes were also involved and presented bilateral papilledema.Genetic testing revealed that the symptoms were caused by a novel gene mutation site(c.913G>A,p.D305N)in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA.The patient had the characteristic facial features,frontal fossa and saddle nose,manifested the generalized urticaria-like skin rash at two weeks after birth,periodic fever 6 months after birth,sensorineural deafness at 7 years old,and bilateral papilledema,aseptic meningitis and knee arthropathy at 9 years old.White cell counts,C-reactive protein increased and intracranial pressure raised to 300 mmH2O.The meningeal thickening enhanced by gadolinium in magnetic resonance imaging(MRI).Based on clinical features and genetic test,the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms.With 3-year follow-up,patient had no inflammatory flare-up with visual acuity improvement.The finding of novel genetic mutation site(p.D305N)in NLRP3 gene expanded genotype spectrum associated with CINCA.This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.
文摘目的探讨慢性婴儿神经、皮肤、关节综合征(CINCA)的基因突变、临床表型、治疗及预后情况,从而提高本病的诊断率、降低致残率和致畸率。方法回顾性分析本院诊断的10例CINCA综合征患儿的临床表型、辅助检查、治疗及随访情况。经家长同意后取患儿及父母各3 ml EDTA抗凝血,用QIAamp全血DNA提取试剂盒(德国Qiagen公司)提取基因组DNA,应用Agilent液相捕获目标基因技术(Agilent公司)进行全外显子基因检测,最后应用Sanger测序法进行验证。结果本研究共发现CINCA综合征患儿NLRP3基因有8个杂合突变位点,分别是913G/A(D305N)、1057G/T(V353L)、1702T/A(F568I)、1703T/A(F568Y)、1710G/C(K570N)、1789A/G(S597G)、1991T/C(M664T)、2269G/A(G757R)。本病多数于生后半月起病,起病表现主要是荨麻疹样皮疹。10例患儿均可见身材矮小和特殊面容。所有患儿病程中均有不同程度发热和荨麻疹样皮疹,9例患儿有明显的关节炎,9例患儿有中枢神经系统受累的表现。8例患儿存在双耳神经性耳聋,7例患儿出现双眼视神经炎,6例患儿有肝脾和/或淋巴结肿大。淀粉样蛋白A明显升高。糖皮质激素和免疫抑制剂是治疗本病的基本用药,疗效不佳者需早期加用生物制剂缓解病情。结论CINCA综合征是一种罕见的常染色体显性遗传性疾病,以皮肤、关节和中枢神经系统受累为主要表现,可合并脏器淀粉样变性,早期诊断和治疗可以减少重要脏器受累。
