Johanna van der Put1, Dalia Daugeliene1, Åsa Bergendal1, Malin Kvarnung1, Per Svenningsson1, Martin Paucar1. 1. Department of Clinical Neuroscience (J.v.d.P., Å.B., P.S., M.P.), Karolinska Institutet; Department of Pediatric Neurology (D.D.), Sachska Child Hospital; Department of Clinical Genetics (M.K.), and Department of Neurology (P.S., M.P.), Karolinska University Hospital, Stockholm, Sweden.
Abstract
Objectives: Sporadic variants in ataxia genes may mimic cerebral palsy (CP). Spinocerebellar ataxia 21 (SCA21), a very rare autosomal dominant disease, was discovered to be associated with variants in the transmembrane protein 240 (TMEM240) gene in 2014. In this report, we present 2 patients with sporadic SCA21, one of them diagnosed with ataxic CP. Methods: Patients provided oral and written consent. Comprehensive clinical evaluation, neuroimaging studies, review of previous psychometric evaluations, and whole-genome sequencing were applied in both cases. Results: Both patients presented with early-onset ataxia and exhibited mild parkinsonian features. Patient 1 experienced motor and speech delay, autism, and dyslexia, whereas patient 2 experienced dyslexia. Neuroimaging was normal in both cases. In patient 1, the previously reported pathogenic c.509C>T (Pro170Leu) variant in TMEM240 was detected, whereas patient 2 harbored the novel c.182_188delinsGGAT (Val61_Pro63delinsGlyMet) variant in the same gene. Both genetic variants were sporadic. Discussion: Our findings support the notion that SCA21 is a neurodevelopmental syndrome and a mimicker of ataxic CP. Both lack of a family history of ataxia and congenital presentation were reasonable arguments to consider ataxic CP. However, lack of convincing perinatal incidents, progressive symptoms, and the common presence of cerebellar atrophy should alert neurologists about SCA21.
Objectives: Sporadic variants in ataxia genes may mimic cerebral palsy (CP). Spinocerebellar ataxia 21 (SCA21), a very rare autosomal dominant disease, was discovered to be associated with variants in the transmembrane protein 240 (TMEM240) gene in 2014. In this report, we present 2 patients with sporadic SCA21, one of them diagnosed with ataxic CP. Methods: Patients provided oral and written consent. Comprehensive clinical evaluation, neuroimaging studies, review of previous psychometric evaluations, and whole-genome sequencing were applied in both cases. Results: Both patients presented with early-onset ataxia and exhibited mild parkinsonian features. Patient 1 experienced motor and speech delay, autism, and dyslexia, whereas patient 2 experienced dyslexia. Neuroimaging was normal in both cases. In patient 1, the previously reported pathogenic c.509C>T (Pro170Leu) variant in TMEM240 was detected, whereas patient 2 harbored the novel c.182_188delinsGGAT (Val61_Pro63delinsGlyMet) variant in the same gene. Both genetic variants were sporadic. Discussion: Our findings support the notion that SCA21 is a neurodevelopmental syndrome and a mimicker of ataxic CP. Both lack of a family history of ataxia and congenital presentation were reasonable arguments to consider ataxic CP. However, lack of convincing perinatal incidents, progressive symptoms, and the common presence of cerebellar atrophy should alert neurologists about SCA21.
Authors: Isabelle Vuillaume; David Devos; Susanna Schraen-Maschke; Christian Dina; Arnaud Lemainque; Francis Vasseur; Guy Bocquillon; Patrick Devos; Carole Kocinski; Christiane Marzys; Alain Destée; Bernard Sablonnière Journal: Ann Neurol Date: 2002-11 Impact factor: 10.422
Authors: Emma D Burdekin; Brent L Fogel; Shafali S Jeste; Julian Martinez; Jessica E Rexach; Charlotte DiStefano; Carly Hyde; Tabitha Safari; Rujuta B Wilson Journal: J Child Neurol Date: 2020-07-24 Impact factor: 1.987
Authors: J Delplanque; D Devos; I Vuillaume; A De Becdelievre; E Vangelder; C A Maurage; K Dujardin; A Destée; B Sablonnière Journal: Cerebellum Date: 2008 Impact factor: 3.847