Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2019) 7 P125 | DOI: 10.1530/boneabs.7.P125

ICCBH2019 Poster Presentations (1) (226 abstracts)

SCN8a mutations and osteoporosis. Is osteocyte dysfunction the cause or the consequence?

Gillian O’Donnell 1 , Leah Halpenny 3 , Eleanor Burke 1 , Laura McCarron 1 , Sabrina Sheridan 1 & Ciara McDonnell 1,

1Department of Paediatric Endocrinology, Temple Street Children’s University Hospital, Dublin, Ireland; 2Discipline of Paediatrics, University of Dublin, Trinity College, Dublin, Ireland; 3Department of Paediatric Neurology, Temple Street Children’s University Hospital, Dublin, Ireland.

Background: Mutations in the SCN8a gene, which encodes one of the most abundant voltage gated sodium channels; Nav1.6, has a strong association with epileptic encephalopathy type 13, ataxia, muscle atrophy and intellectual disability. Previous cases of pathological skeletal fractures in children with known SCN8a mutations have been published but the source of the related skeletal mechanism remains unclear.

Presenting problem: The proband presented at 15months of age to our service with a diagnosis of infantile epileptic encephalopathy due to a known SCN8a variant (c.4400T>G,Phel1467Cys). She was born at term following normal pregnancy to non-consanguineous Caucasian Irish parents. She developed jittery episodes postnatally which evolved into seizures unresponsive to phenobarbitone and clonazepam. She is currently managed on sodium valproate and topiramate. Fractures of the right femur, radius and left femur have been picked up on X-ray imaging precipitated by reduced limb movement following intractable seizure activity at 15 months and again at 20 months.

Clinical management: Biochemical markers of bone turnover were consistent with normal bone metabolism and mineralization. She was commenced on vitamin D supplementation due to her anti-epileptic medications. She proceeded to bone biopsy analysis. This showed increased osteoclast numbers and high osteocyte density with unmineralized peri-osteocytic areas suggestive of osteocyte dysfunction. Bisphosphonate treatment with Zoledronic acid was initiated at 21 months of age and there have been no further fractures despite further episodes of generalised seizure activity.

Discussion: Pathological fractures in intractable epilepsy are often attributed to trauma incurred during seizure activity, disuse osteoporosis secondary to neurological or the result of multiple anti-epileptic medications. We postulate that the cause is her underlying mutation resulting in osteocyte dysfunction. Case reports of children with severe juvenile osteoporosis affected by this mutation have been published but have not reported bone histomorphometry. A homozygous SCN8A null mouse model has shown increased osteoclastogenesis suggesting the involvement of the Nav1.6 voltage gated sodium channel in skeletal turnover. Treatment with bisphosphonates has led to successful fracture prevention. We advocate that individuals with SCN8a mutations should receive surveillance for skeletal complications and may benefit from initiation of bisphosphonate treatment.

Disclosure: The authors declared no competing interests.

Volume 7

9th International Conference on Children's Bone Health


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