The Natural Course of Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

IF 2.9 3区 医学 Q2 GENETICS & HEREDITY
Ilia Valentin, Pilar Caro, Christine Fischer, Heiko Brennenstuhl, Christian P Schaaf
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引用次数: 0

Abstract

(Likely) pathogenic variants in NR2F1 are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS, OMIM #615722), a rare neurodevelopmental disorder. Patients present with a variety of symptoms, including intellectual disability, developmental delay, visual impairment, muscular hypotonia, seizures, and/or autistic features. Since it was first described in 2014, the phenotype has steadily expanded. However, there is limited information regarding the natural course of the disorder. Here, we present data on genetic variants and phenotype development of 47 individuals who responded to our questionnaire. A questionnaire was developed to assess the phenotype more comprehensively and to better understand the course of symptoms. In addition, families sent medical documents and photographs. To investigate the genotype-phenotype correlation in our cohort, we compared clinical features of two genotypically distinct groups (variants in the DNA-binding domain (DBD, n = 17) versus variants elsewhere in the gene (n = 30)). We observed a range of common symptoms including developmental delay, muscular hypotonia, optic atrophy, nystagmus, strabismus, autistic features, and thin corpus callosum on brain MRI. Overall, more improvement than worsening was reported. Individuals with variants in the DBD showed a higher prevalence of severe clinical features, such as infantile spasms (46.7% vs. 3.8%, p = 0.002) or nonverbality (50% vs. 3.4%, p = 0.0004), age at diagnosis was statistically significantly different between the two genotypic groups (mean 4.7 years vs. 8.9 years, p = 0.048). Our study confirms characteristic clinical features of BBSOAS. Variants in the DBD are associated with a more severe clinical phenotype. We found no evidence that the disease progresses; rather, several symptoms are reported to improve over time. However, prospective longitudinal studies are needed to further investigate disease progression.

Bosch-Boonstra-Schaaf视神经萎缩综合征的自然病程。
(可能的)NR2F1致病变异与Bosch-Boonstra-Schaaf视神经萎缩综合征(BBSOAS, OMIM #615722)有关,这是一种罕见的神经发育障碍。患者表现出多种症状,包括智力残疾、发育迟缓、视力损害、肌肉张力减退、癫痫发作和/或自闭症特征。自2014年首次被描述以来,这种表型一直在稳步扩大。然而,关于这种疾病的自然过程的信息有限。在这里,我们提供了47个回答我们问卷的个体的遗传变异和表型发展的数据。为了更全面地评估表现型和更好地了解症状的过程,我们开发了一份问卷。此外,家属送来了医疗文件和照片。为了研究我们的队列中基因型-表型的相关性,我们比较了两个基因典型不同组的临床特征(dna结合域的变异(DBD, n = 17)和基因其他部位的变异(n = 30))。我们在脑MRI上观察到一系列常见症状,包括发育迟缓、肌肉张力减退、视神经萎缩、眼球震颤、斜视、自闭症特征和胼胝体薄。总体而言,报告的改善多于恶化。DBD变异个体表现出更高的严重临床特征患病率,如婴儿痉挛(46.7%对3.8%,p = 0.002)或非语言(50%对3.4%,p = 0.0004),诊断年龄在两个基因型组之间有统计学差异(平均4.7岁对8.9岁,p = 0.048)。我们的研究证实了BBSOAS的典型临床特征。DBD的变异与更严重的临床表型相关。我们没有发现疾病进展的证据;相反,有几种症状会随着时间的推移而改善。然而,需要前瞻性的纵向研究来进一步调查疾病的进展。
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来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
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