SUN-742 - Case of Pathological Fractures in 2-Year-Old Male with SCN8A Gene Mutation

The SCN8A gene, identified in 1995, encodes one of the most abundant voltage-gated sodium channels in the brain, therefore, mutations of this gene are well-studied in relation to neurological disorders.[1] Its involvement in bone health is not widely understood. Few case reports have detailed the phenotypic presentation of epileptic encephalopathy accompanied by pathological fractures in the presence of SCN8A gene mutations, with a 6-year-old representing the youngest case in the literature of concurrent juvenile osteoporosis. In the presence of such mutation, there is evidence of reduced trabecular number and thickness, cortical thinning, and increased skeletal turnover with increased osteoclastogenesis.[1] Anti-resorptive treatments have shown to improve bone microstructure as well as reduce osteoclastogenic activity.[2]

We present a case of a 3-year-old male who initially presented to a children’s hospital at 2 months of age for episodes of apnea, cyanosis and hypotonia. Hospitalization resulted in a negative cardiology work-up. After a vEEG and MRI resulted normal, genetics was consulted to evaluate seizure etiology. Patient was having seizures up to 7 episodes per day. An epilepsy genetic panel resulted in one heterozygous pathogenic variant mutation of the SCN8A gene c.4423G>A (p.Gly1475Arg). This gene mutation is most often associated with autosomal dominant disorders ranging from benign familial neonatal seizures to epileptic encephalopathy. Patient was placed on Keppra and Phenobarbital.

Between 2 and 3 years of age, patient experienced 6 fractures (left distal femur, left proximal femur, right distal radius, left femoral neck, left tibia, and left fibula). Endocrinology was consulted given severity of fractures. Labs indicated normal calcium, magnesium, phosphorus, alkaline phosphatase, and vitamin D. Further research revealed that mutations in the SCN8A gene are correlated with severe juvenile osteoporosis, characterized by multiple skeletal fractures, resembling the clinical presentation observed in this case. Biphosphonate treatment, with Zoledronic Acid infusions, was recommended and started.

This case underscores the importance of bone health assessments in patients with SCN8A gene mutations. While this patient had multiple risk factors for bone fragility including disuse osteoporosis, nutritional challenges due to gastrostomy-tube feedings, recurrent tonic-clonic seizures, and exposure to anti-epileptic medications, the genetic mutation further prompted bone fragility. Care of patients with SCN8A mutations generally centers around decreasing seizures and improving cognitive function; however, early anti-resorptive treatments may aid in preventing fractures. In our case study, the patient-initiated bisphosphonate therapy at 2 years and 10 months post-diagnosis.

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