Juan Francisco Vázquez-Costa1,2,3, Laia Pedrola Vidal4, Sarah Moreau-Le Lan4, Irene Teresí-Copoví5, Marina Frasquet1,2,3, Maria J Chumillas1,3,5, Teresa Sevilla1,2,3,6. 1. a Instituto de Investigación Sanitaria la Fe (IIS La Fe) , Neuromuscular Research Unit , Valencia , Spain. 2. b Department of Neurology , ALS Unit, Hospital Universitario y Politécnico La Fe , Valencia , Spain. 3. c Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Valencia , Spain. 4. d Instituto de Investigación Sanitaria La Fe , Genomic Unit , Valencia , Spain. 5. e Department of Neurophysiology , ALS Unit, Hospital Universitario y Politécnico La Fe , Valencia , Spain. 6. f Department of Medicine , University of Valencia , Valencia , Spain.
Abstract
Objective: To describe a patient with facial onset sensory and motor neuronopathy (FOSMN) carrying heterozygous mutations in both TARDBP and SQSTM1 genes. Methods: The patient underwent neurological, neuropsychological, and neurophysiological examinations. Brain magnetic resonance imaging (MRI) and extensive genetic analysis were also performed. Results: The neurological examination showed dysphonia, left trigeminal hypesthesia, and left masseter and temporalis muscle atrophy. Mild cognitive impairment, affecting predominantly executive functions and social cognition, was appreciable in the neuropsychological examination. The electrophysiological studies revealed: left abnormal blink reflex; neurogenic changes in bulbar and cervical muscles; normal motor evoked potential amplitude, central motor conduction time and cortical silent period. Brain MRI showed right-predominant frontotemporal atrophy. Genetic analysis showed a heterozygous mutation in TARDBP (p.A390S) and in SQSTM1 (p.P392L), both previously described as causing amyotrophic lateral sclerosis. The SQSTM1, but not the TARDBP, mutation was found in both healthy siblings. Conclusions: Our data provide new clinical, neuroimaging, and genetic evidence that FOSMN is a neurodegenerative disease of the motor neuron disease and frontotemporal dementia spectrum, with a possible oligogenic origin. Multicentric efforts focusing on cognitive and genetic studies are necessary to confirm this hypothesis and to determine if ALS genes should be systematically screened in these patients.
Objective: To describe a patient with facial onset sensory and motor neuronopathy (FOSMN) carrying heterozygous mutations in both TARDBP and SQSTM1 genes. Methods: The patient underwent neurological, neuropsychological, and neurophysiological examinations. Brain magnetic resonance imaging (MRI) and extensive genetic analysis were also performed. Results: The neurological examination showed dysphonia, left trigeminal hypesthesia, and left masseter and temporalis muscle atrophy. Mild cognitive impairment, affecting predominantly executive functions and social cognition, was appreciable in the neuropsychological examination. The electrophysiological studies revealed: left abnormal blink reflex; neurogenic changes in bulbar and cervical muscles; normal motor evoked potential amplitude, central motor conduction time and cortical silent period. Brain MRI showed right-predominant frontotemporal atrophy. Genetic analysis showed a heterozygous mutation in TARDBP (p.A390S) and in SQSTM1 (p.P392L), both previously described as causing amyotrophic lateral sclerosis. The SQSTM1, but not the TARDBP, mutation was found in both healthy siblings. Conclusions: Our data provide new clinical, neuroimaging, and genetic evidence that FOSMN is a neurodegenerative disease of the motor neuron disease and frontotemporal dementia spectrum, with a possible oligogenic origin. Multicentric efforts focusing on cognitive and genetic studies are necessary to confirm this hypothesis and to determine if ALS genes should be systematically screened in these patients.
Authors: Eva M J de Boer; Andrew W Barritt; Marwa Elamin; Stuart J Anderson; Rebecca Broad; Angus Nisbet; H Stephan Goedee; Juan F Vázquez Costa; Johannes Prudlo; Christian A Vedeler; Julio Pardo Fernandez; Mónica Povedano Panades; Maria A Albertí Aguilo; Eleonora Dalla Bella; Giuseppe Lauria; Wladimir B V R Pinto; Paulo V S de Souza; Acary S B Oliveira; Camilo Toro; Joost van Iersel; Malu Parson; Oliver Harschnitz; Leonard H van den Berg; Jan H Veldink; Ammar Al-Chalabi; Peter N Leigh; Michael A van Es Journal: Neurol Clin Pract Date: 2021-04