■Joubert综合征(JBTS,OMIM#213300)是一组以中脑后脑畸形为特征的纤毛病,发育迟缓,低张力,动眼失用症,和呼吸异常。脑成像中的磨牙征是诊断JBTS的标志。它是一种临床和遗传异质性疾病,涉及40多个纤毛病相关基因的突变。然而,长期随访数据很少,需要进一步的研究来确定这种疾病的丰富表型和遗传学。本研究旨在总结临床表现,特别是在颅骨成像上的外观,遗传数据,和JBTS患者的预后特征。
■对1986年5月至2021年12月的36例JBTS进行了回顾性病例回顾。分析以发育迟缓和颅骨影像学上磨牙征为主要特征的JBTS患者的临床资料。根据患者及其家属的同意进行基因检测。采用Gesell发育量表评价治疗前后的智力水平。将患儿分为单纯神经JBTS(pureJBTS)组和多器官系统受累JBTS组,每3~6个月随访一次。
■我们招募了18名男性和18名女性。34例(94.44%)有发育迟缓,1例(2.78%)斜视,1例(2.78%)出现间歇性头晕。有一例与Lesch-Nyhan综合征共病。四分之三的病例有一个或多个其他器官或系统受累,更倾向于视力和听力受损。JBTS也可能涉及皮肤。31例(86.11%)表现为典型的磨牙征,5例头颅成像显示蝙蝠翼征。7.69%的病例获得了异常视频脑电图(VEEG)结果。我们发现了六个与JBTS相关的新基因位点变异:CPLANE1:c.4189+1G>A,C.3101T>C(p。Ile1034Thr),c.3733T>C(p。Cys1245Arg),c.4080G>A(p。Lys1360=);RPGRIP1l:c.1351-11A>G;CEP120:c.214C>T(p。Arg72Cys)。CHD7基因可能与JBTS的发生有关。经正规康复治疗后,单纯JBTS的预后优于神经和非神经受累的JBTS(P<0.05)。在三个癫痫发作的孩子中,2例癫痫患者预后不良,另一个案例有屏住呼吸的咒语。
■我们的发现表明,早期颅骨成像有助于无法解释的发育迟缓和多发性畸形儿童的病因诊断。JBTS患者可能同时存在皮肤异常。CPLANE1的新基因位点,RPGRIP1l,在我们的研究中,CEP120与JBTS相关,并提供了丰富相关遗传数据的重要信息。未来研究CHD7基因与JBTS之间关联的几个方面的工作值得进一步研究。单纯JBTS患儿的预后优于非神经系统受累JBTS患儿。
UNASSIGNED: Joubert syndrome (JBTS, OMIM # 213300) is a group of ciliopathies characterized by mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia, and breathing abnormalities. Molar tooth sign in brain imaging is the hallmark for diagnosing JBTS. It is a clinically and genetically heterogeneous disorder involving mutations in more than 40 ciliopathy-related genes. However, long-term follow-up data are scarce, and further research is needed to determine the abundant phenotypes and genetics of this disorder. The study aimed to summarize clinical manifestations, particular appearance on cranial imaging, genetic data, and prognostic features of patients with JBTS.
UNASSIGNED: A retrospective case review of 36 cases of JBTS from May 1986 to December 2021 was performed. Clinical data of JBTS patients with development retardation and molar tooth sign on cranial imaging as the main features were analyzed. Genetic testing was performed according to consent obtained from patients and their families. The Gesell Developmental Scale was used to evaluate the intelligence level before and after treatment. The children were divided into a purely neurological JBTS (pure JBTS) group and JBTS with multi-organ system involvement group and then followed up every 3-6 months.
UNASSIGNED: We enrolled 18 males and 18 females. Thirty-four (94.44%) cases had developmental delay, one patient (2.78%) had strabismus, and one patient (2.78%) had intermittent dizziness. There was one case co-morbid with Lesch-Nyhan syndrome. Three-quarters of cases had one or more other organ or system involvement, with a greater predilection for vision and hearing impairment. JBTS could also involve the skin. Thirty-one cases (86.11%) showed a typical molar tooth sign, and five cases showed a bat wing sign on cranial imaging. Abnormal video electroencephalogram (VEEG) result was obtained in 7.69% of cases. We found six JBTS-related novel gene loci variants: CPLANE1: c.4189 + 1G > A, c.3101T > C(p.Ile1034Thr), c.3733T > C (p.Cys1245Arg), c.4080G > A(p.Lys1360=); RPGRIP1l: c.1351-11A > G; CEP120: c.214 C > T(p.Arg72Cys). The CHD7 gene may be potentially related to the occurrence of JBTS. Analysis showed that the prognosis of pure JBTS was better than that of JBTS with neurological and non-neurological involvement after the formal rehabilitation treatment (P < 0.05). Of the three children with seizures, two cases had epilepsy with a poor prognosis, and another case had breath-holding spells.
UNASSIGNED: Our findings indicate that early cranial imaging is helpful for the etiological diagnosis of children with unexplained developmental delay and multiple malformations. Patients with JBTS may have coexisting skin abnormalities. The novel gene loci of CPLANE1, RPGRIP1l, and CEP120 were associated with JBTS in our study and provided significant information to enrich the related genetic data. Future works investigating several aspects of the association between CHD7 gene and JBTS merit further investigation. The prognosis of children with pure JBTS is better than that of children with JBTS with non-neurological involvement.