Huddar Akshata, Polavarapu Kiran, Preethish-Kumar Veeramani, Bardhan Mainak, Unnikrishnan Gopikrishnan, Nashi Saraswati, Vengalil Seena, Priyadarshini Priyanka, Kulanthaivelu Karthik, Arunachal Gautham, Lochmüller Hanns, Nalini Atchayaram
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India.
Children's Hospital of Eastern Ontario Research Institute, Department of Medicine, Division of Neurology, The Ottawa Hospital, Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
Children (Basel). 2021 Oct 13;8(10):909. doi: 10.3390/children8100909.
Distal arthrogryposis type 5D (DA5D), a rare autosomal recessive disorder, is caused by mutations in We describe two consanguineous families (three patients) with novel gene mutations detected by next-generation sequencing (NGS). A 12-year-old boy (patient 1) presented with birth asphyxia, motor developmental delay, multiple joint contractures, pes planus, kyphoscoliosis, undescended testis, hypophonic speech with a nasal twang, asymmetric ptosis, facial weakness, absent abductor pollicis brevis, bifacial, and distal lower limb weakness. Muscle MRI revealed asymmetric fatty infiltration of tensor fascia lata, hamstring, lateral compartment of the leg, and gastrocnemius. In addition, 17-year-old monozygotic twins (patients 2 and 3) presented with motor development delay, white hairlock, hypertelorism, tented upper lip, bulbous nose, tongue furrowing, small low set ears, multiple contractures, pes cavus, prominent hyperextensibility at the knee, hypotonia of lower limbs, wasting and weakness of all limbs (distal > proximal), areflexia, and high steppage gait. One had perinatal insult, seizures, mild intellectual disability, unconjugated eye movements, and primary optic atrophy. In the twins, MRI revealed extensive fatty infiltration of the gluteus maximus, quadriceps, hamstrings, and anterior and posterior compartment of the leg. Electrophysiology showed prominent motor axonopathy. NGS revealed rare homozygous missense variants c.602T > C (p.Met201Thr) in patient 1 and c.83C > T (p.Ala28Val) in patients 2 and 3, both localized in exon 2 of gene. Our three cases expand the clinical, imaging, and molecular spectrum of the -mutation-related DA5D.
5D型远端关节弯曲综合征（DA5D）是一种罕见的常染色体隐性疾病，由 基因的突变引起。我们描述了两个近亲家庭（三名患者），通过下一代测序（NGS）检测到了新的基因突变。一名12岁男孩（患者1）出生时出现窒息、运动发育迟缓、多关节挛缩、扁平足、脊柱侧凸、隐睾、带有鼻音的低音调言语、不对称上睑下垂、面部肌无力、拇短展肌缺失、双侧面瘫以及下肢远端肌无力。肌肉磁共振成像显示阔筋膜张肌、腘绳肌、小腿外侧肌群和腓肠肌存在不对称性脂肪浸润。此外，一对17岁的同卵双胞胎（患者2和患者3）表现为运动发育迟缓、白色发绺、眼距增宽、上唇紧绷、球状鼻、舌沟、低位小耳、多处挛缩、高弓足、膝关节明显过度伸展、下肢张力减退、四肢（远端>近端）消瘦和无力、无反射以及高抬腿步态。其中一人有围产期损伤、癫痫发作、轻度智力残疾、非共轭眼球运动和原发性视神经萎缩。在这对双胞胎中，磁共振成像显示臀大肌、股四头肌、腘绳肌以及小腿前后肌群广泛脂肪浸润。电生理学显示明显的运动轴索性神经病。NGS显示患者1存在罕见的纯合错义变体c.602T > C（p.Met201Thr），患者2和患者3存在c.83C > T（p.Ala28Val），两者均位于 基因的第2外显子。我们的三例病例扩展了与 基因突变相关的DA5D的临床、影像学和分子谱。
