Craiu Dana, Dragostin Octavia, Dica Alice, Hoffman-Zacharska Dorota, Gos Monika, Bastian Alexandra Eugenia, Gherghiceanu Mihaela, Rolfs Arndt, Nahavandi Nahid, Craiu Mihai, Iliescu Catrinel
"Carol Davila" University of Medicine Bucharest, Department of Neurology, Pediatric Neurology, Psychiatry, Neurosurgery, Discipline Pediatric Neurology, Romania; Pediatric Neurology Clinic, "Alexandru Obregia" Clinical Psychiatric Hospital, Şos. Berceni 10-12, Sector 4, Bucharest, Romania.
Pediatric Neurology Clinic, "Alexandru Obregia" Clinical Psychiatric Hospital, Şos. Berceni 10-12, Sector 4, Bucharest, Romania.
Eur J Paediatr Neurol. 2015 Jan;19(1):78-86. doi: 10.1016/j.ejpn.2014.07.008. Epub 2014 Aug 7.
We present clinical and molecular findings of a patient with ceroid-lipofuscinosis CLN7, with a compound heterozygous mutation of the MFSD8 gene, with Rett syndrome clinical signs onset and a later development of full picture of vLINCL.
A 7 years-old female patient with normal development until the age 12 months, developed Rett like clinical picture (psychomotor regression, microcephaly, stereotypic hands movements in the midline, hyperventilation episodes) present at the onset of her condition (age 18 months), features still present at the initial evaluation in our clinic at age 5 years.
MECP2 (methyl CpG binding protein 2) gene mutation was negative. At age 6 years she was readmitted for severe ataxia and blindness, seizures, and severe developmental regression leading to NCL (neuronal ceroid lipofuscinosis) suspicion. EEG showed slow background with IRDA (intermittent rhythmic delta activity). A conjunctive biopsy showed abnormal curvilinear and fingerprint lysosomal deposits, and genetic analysis revealed two heterozygous mutations of MFSD8 gene (c.881C > A p.Thr294Lys and c.754 + 2T > A) each inherited from carrier parents and a heterozygous variant (c.470A>C p.Asp157Ala) of CLN5 gene.
NCL should be suspected and MFSD8 genetic testing should also be considered in patients with Rett like phenotype at onset and negative MECP2 mutation. Such cases should be carefully and frequently re-evaluated in order to avoid delayed diagnosis and offer proper genetic advice to the family. In our knowledge, this might be the first case of CLN7 disease with Rett like onset described in the literature, which developed typical vLINCL clinical phenotype after age 5.5 years. A short review of the literature showing NCL onset modalities is presented.
我们报告了一名患有CLN7型蜡样脂褐质沉积症患者的临床和分子学研究结果，该患者存在MFSD8基因复合杂合突变，临床表现为雷特综合征，随后发展为典型的晚发型神经元蜡样脂褐质沉积症（vLINCL）。
一名7岁女性患者，12个月前发育正常，18个月大时出现类似雷特综合征的临床表现（精神运动发育倒退、小头畸形、中线刻板手部动作、呼吸急促发作），在5岁初次到我们诊所评估时这些症状仍然存在。
甲基化CpG结合蛋白2（MECP2）基因突变检测为阴性。6岁时，她因严重共济失调、失明、癫痫发作及严重发育倒退再次入院，怀疑患有神经元蜡样脂褐质沉积症（NCL）。脑电图显示背景活动缓慢伴有间歇性节律性δ活动（IRDA）。联合活检显示异常的曲线形和指纹状溶酶体沉积，基因分析发现MFSD8基因有两个杂合突变（c.881C>A，p.Thr294Lys和c.754+2T>A），分别遗传自携带突变的父母，同时还发现CLN5基因有一个杂合变异（c.470A>C，p.Asp157Ala）。
对于起病时具有类似雷特综合征表型且MECP2基因突变阴性的患者，应怀疑NCL并考虑进行MFSD8基因检测。对此类病例应进行仔细且频繁的重新评估，以避免诊断延迟并为家庭提供适当的遗传咨询。据我们所知，这可能是文献中报道的首例以类似雷特综合征起病的CLN7疾病，该患者在5.5岁后发展为典型的vLINCL临床表型。本文还简要回顾了显示NCL起病方式的文献。
