Expanding the Phenotypic Spectrum of <i>ECEL1</i>-Associated Distal Arthrogryposis
Akshata Huddar,
Kiran Polavarapu,
Veeramani Preethish-Kumar,
Mainak Bardhan,
Gopikrishnan Unnikrishnan,
Saraswati Nashi,
Seena Vengalil,
Priyanka Priyadarshini,
Karthik Kulanthaivelu,
Gautham Arunachal,
Hanns Lochmüller,
Atchayaram Nalini
Affiliations
Akshata Huddar
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Kiran Polavarapu
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
Veeramani Preethish-Kumar
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Mainak Bardhan
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Gopikrishnan Unnikrishnan
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Saraswati Nashi
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Seena Vengalil
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Priyanka Priyadarshini
Department of Neuro Imaging and Interventional Radiology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Karthik Kulanthaivelu
Department of Neuro Imaging and Interventional Radiology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Gautham Arunachal
Department of Human Genetics, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Hanns Lochmüller
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
Atchayaram Nalini
Department of Neurology, National Institute of Mental Health and Neuro-Sciences, Bengaluru 560029, India
Distal arthrogryposis type 5D (DA5D), a rare autosomal recessive disorder, is caused by mutations in ECEL1. We describe two consanguineous families (three patients) with novel ECEL1 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 ECEL1 gene. Our three cases expand the clinical, imaging, and molecular spectrum of the ECEL1-mutation-related DA5D.
