TY - JOUR
T1 - Charcot-Marie-Tooth disease with pyramidal features due to a new mutation of EGR2 gene
AU - Fusco, Carlo
AU - Spagnoli, Carlotta
AU - Salerno, Grazia Gabriella
AU - Pavlidis, Elena
AU - Frattini, Daniele
AU - Pisani, Francesco
AU - Bassi, Maria Teresa
PY - 2019/1/24
Y1 - 2019/1/24
N2 - BACKGROUND AND AIM OF THE WORK: Childhood-onset peripheral neuropathies are often of genetic origin. Charcot-Marie-Tooth (CMT), is considered the commonest neuromuscular disorder. Due to its high clinical heterogeneity, especially in the pediatric age, the co-existence of central and peripheral symptoms and signs does not necessarily rule out a diagnosis of hereditary peripheral neuropathy. METHODS: We describe the clinical, neurophysiological and genetic findings in a teen-age patient evaluated for acquired toe-walking and progressive difficulties in walking since the age of 5. Genetic testing was carried out with a targeted NGS panel. Identified variants are analyzed using Variant Studio program (Illumina). Rare variants and variants considered as pathogenic were analyzed by Sanger direct sequencing. RESULTS: The coexistence of peripheral and pyramidal signs in the lower limbs, the absence of a significant pre/perinatal history, the unremarkable brain and spine MRI, together with the presence of a sensory-motor polyneuropathy in all four limbs, prompted the execution of genetic investigations with an NGS panel covering hereditary spastic paraplegias, motor neuron disease and Charcot-Marie-Tooth. We identified a previously undescribed variant (c.1142G>T, p.Arg381Leu) in the EGR2 gene. CONCLUSIONS: ERG2 gene has been described as a cause of various phenotypes, including a rare autosomal dominant form of CMT (CMT type 1D) representing approximately 1% of all CMT subgroups. We describe a novel pathogenic variant in EGR2 gene leading to the development of a complex association of peripheral and central neurological signs, underscoring the genetic and clinical heterogeneity of hereditary neuropathies of pediatric onset.
AB - BACKGROUND AND AIM OF THE WORK: Childhood-onset peripheral neuropathies are often of genetic origin. Charcot-Marie-Tooth (CMT), is considered the commonest neuromuscular disorder. Due to its high clinical heterogeneity, especially in the pediatric age, the co-existence of central and peripheral symptoms and signs does not necessarily rule out a diagnosis of hereditary peripheral neuropathy. METHODS: We describe the clinical, neurophysiological and genetic findings in a teen-age patient evaluated for acquired toe-walking and progressive difficulties in walking since the age of 5. Genetic testing was carried out with a targeted NGS panel. Identified variants are analyzed using Variant Studio program (Illumina). Rare variants and variants considered as pathogenic were analyzed by Sanger direct sequencing. RESULTS: The coexistence of peripheral and pyramidal signs in the lower limbs, the absence of a significant pre/perinatal history, the unremarkable brain and spine MRI, together with the presence of a sensory-motor polyneuropathy in all four limbs, prompted the execution of genetic investigations with an NGS panel covering hereditary spastic paraplegias, motor neuron disease and Charcot-Marie-Tooth. We identified a previously undescribed variant (c.1142G>T, p.Arg381Leu) in the EGR2 gene. CONCLUSIONS: ERG2 gene has been described as a cause of various phenotypes, including a rare autosomal dominant form of CMT (CMT type 1D) representing approximately 1% of all CMT subgroups. We describe a novel pathogenic variant in EGR2 gene leading to the development of a complex association of peripheral and central neurological signs, underscoring the genetic and clinical heterogeneity of hereditary neuropathies of pediatric onset.
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U2 - 10.23750/abm.v90i1.6951
DO - 10.23750/abm.v90i1.6951
M3 - Article
C2 - 30889162
AN - SCOPUS:85063288798
VL - 90
SP - 104
EP - 107
JO - Acta Biomedica de l'Ateneo Parmense
JF - Acta Biomedica de l'Ateneo Parmense
SN - 0392-4203
IS - 1
ER -