Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy
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Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy. / Rolvien, Tim; Butscheidt, Sebastian; Jeschke, Anke; Neu, Axel; Denecke, Jonas; Kubisch, Christian; Meisler, Miriam H; Püschel, Klaus; Barvencik, Florian; Yorgan, Timur; Oheim, Ralf; Schinke, Thorsten; Amling, Michael.
In: BONE, Vol. 103, 10.2017, p. 136-143.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy
AU - Rolvien, Tim
AU - Butscheidt, Sebastian
AU - Jeschke, Anke
AU - Neu, Axel
AU - Denecke, Jonas
AU - Kubisch, Christian
AU - Meisler, Miriam H
AU - Püschel, Klaus
AU - Barvencik, Florian
AU - Yorgan, Timur
AU - Oheim, Ralf
AU - Schinke, Thorsten
AU - Amling, Michael
N1 - Copyright © 2017. Published by Elsevier Inc.
PY - 2017/10
Y1 - 2017/10
N2 - Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juvenile osteoporosis and multiple skeletal fractures, similar to three previous case reports. Skeletal assessment using dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum analyses revealed a combined trabecular and cortical bone loss syndrome with elevated bone resorption. Likewise, when we analyzed the skeletal phenotype of 2week-old Scn8a-deficient mice we observed reduced trabecular and cortical bone mass, as well as increased osteoclast indices by histomorphometric quantification. Based on this cumulative evidence the patient was treated with neridronate (2mg/kg body weight administered every 3months), which fully prevented additional skeletal fractures for the next 25months. Taken together, our data provide evidence for a negative impact of SCN8A mutations on bone mass, which can be positively influenced by anti-resorptive treatment.
AB - Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juvenile osteoporosis and multiple skeletal fractures, similar to three previous case reports. Skeletal assessment using dual energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) and serum analyses revealed a combined trabecular and cortical bone loss syndrome with elevated bone resorption. Likewise, when we analyzed the skeletal phenotype of 2week-old Scn8a-deficient mice we observed reduced trabecular and cortical bone mass, as well as increased osteoclast indices by histomorphometric quantification. Based on this cumulative evidence the patient was treated with neridronate (2mg/kg body weight administered every 3months), which fully prevented additional skeletal fractures for the next 25months. Taken together, our data provide evidence for a negative impact of SCN8A mutations on bone mass, which can be positively influenced by anti-resorptive treatment.
KW - Journal Article
U2 - 10.1016/j.bone.2017.06.025
DO - 10.1016/j.bone.2017.06.025
M3 - SCORING: Journal article
C2 - 28676440
VL - 103
SP - 136
EP - 143
JO - BONE
JF - BONE
SN - 8756-3282
ER -
