Phenotype Analysis in Two Families With Otopalatodigital Syndrome Spectrum Disorder Based on FLNA Gene Variants.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Martin Schwarz, Miroslav Fišer, Lenka Šodková, Eva Míšová, Martin Drahanský, Tomáš Vokálek, Renata Michalovská, Adéla Matějková, Jaroslava Jindrová, Šárka Bendová, Milan Macek
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引用次数: 0

Abstract

Otopalatodigital spectrum disorders (OPDSD), comprising otopalatodigital syndromes types 1 and 2 (OPD1, OPD2) and frontometaphyseal dysplasia (FMD), are rare X-linked disorders caused by FLNA gene variants, with phenotypes ranging from mild skeletal anomalies to severe multisystem malformations. We describe two unrelated cases: a 14-year-old male (P1, FMD) and an aborted fetus (P2, OPD2). Whole-exome sequencing identified hemizygous maternally inherited FLNA gene variants in P1 (c.733G>A; p.Glu245Lys) and P2 (c.3707G>A; p.Gly1236Asp, novel), expanding the OPD2 mutational spectrum (NM_001110556). P1 presented with facial dysmorphism, dental anomalies, flattened thumbs, and dermatoglyphic changes; P2 showed facial dysmorphism, skeletal and cardiac malformations, and omphalocele. These cases underscore the breadth of OPDSD phenotypic variability and add novel genetic data. Dental management demands multidisciplinary care from infancy through adolescence, including cleft repair, orthodontics for micrognathia and facial aesthetics, and treatment of dental anomalies. Early recognition, molecular diagnosis, and coordinated management are critical for improving outcomes in these complex disorders.

基于FLNA基因变异的两家系耳腭指综合征谱系障碍表型分析。
指耳谱系障碍(OPDSD),包括指耳综合征1型和2型(OPD1、OPD2)和额干骺端发育不良(FMD),是由FLNA基因变异引起的罕见的x连锁疾病,其表型从轻度骨骼异常到严重的多系统畸形不等。我们描述了两个不相关的病例:一个14岁的男性(P1, FMD)和一个流产的胎儿(P2, OPD2)。全外显子组测序鉴定出P1 (c.733G>A; p.Glu245Lys)和P2 (c.3707G>A; p.Gly1236Asp, novel)的半合母系遗传FLNA基因变异,扩大了OPD2突变谱(NM_001110556)。P1表现为面部畸形、牙齿异常、拇指扁平、皮纹改变;P2表现为面部畸形、骨骼和心脏畸形以及脐膨出。这些病例强调了OPDSD表型变异性的广度,并增加了新的遗传数据。牙齿管理需要从婴儿期到青春期的多学科护理,包括腭裂修复、小颌畸形的正畸治疗和面部美容,以及牙齿畸形的治疗。早期识别、分子诊断和协调管理对于改善这些复杂疾病的预后至关重要。
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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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