Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the presynaptic neuromuscular junction, typically occurring in adults as a paraneoplastic syndrome. Only rare cases have been reported in childhood. In most childhood cases, malignancies have not been detected but a propensity to autoimmune disease was noticed. Nevertheless, little is known about genetic factors that may contribute to the susceptibility of an individual to develop LEMS. We report on a 13-year-old girl, known with the Xp11.22-p11.23 duplication syndrome, who presented with severe non-paraneoplastic LEMS. The potential role of this microduplication syndrome in the development of LEMS is explored. Previous literature review of twelve Xp11.2 duplication syndrome patients showed that three of them suffered from various autoimmune diseases. The common duplicated region in those three patients and the presented case comprises 12 disease-associated genes including the FOXP3 (Forkhead Box P3) and WAS (Wiskott-Aldrich syndrome) gene, both implicated in immune function. However, it is unclear whether increased gene dosage of one or both of these genes can cause susceptibility to autoimmune diseases. In conclusion, the presented case emphasizes that autoimmune disease is a recurrent feature of the Xp11.2 duplication syndrome, which should be considered in the follow-up of these patients. The exact mechanism underlying this autoimmune propensity remains to be elucidated.
Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Sabine
S
Verbeek
Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
Olivier
O
Vanakker
Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
Rudy
R
Mercelis
Department of Neurology, Leiden University Medical Center, The Netherlands.
A F
AF
Lipka
Department of Pediatrics, Division of Immunology, Ghent University Hospital, Ghent, Belgium.
Filomeen
F
Haerynck
Department of Pneumology, Laboratory for Immunoregulation and Mucosal Immunology, Ghent University Hospital, Ghent, Belgium.
Melissa
M
Dullaers
Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Patrick
P
Verloo
Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Rudy
R
Van Coster
Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium. Electronic address: helene.verhelst@ugent.be.
Helene
H
Verhelst
D000293:Adolescent; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics*; D025063:Chromosome Disorders / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D058674:Chromosome Duplication / Q000235:genetics*; D002658:Developmental Disabilities / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
Chromosome Xp11.23-P11.22 duplication syndrome; Forkhead box P3; Genetic predisposition to autoimmune diseases; Lambert–Eaton myasthenic syndrome; Wiskott–Aldrich syndrome gene