Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Isochromosome Mosaic Turner Syndrome With Epilepsy and Developmental Abnormalities: A Case Report Cesar Prugue, OMS II, Lindsay Tjiattas Saleski, DO, Steven Enkemann, PhD Edward Via College of Osteopathic Medicine, Spartanburg, SC

Abstract

Case Presentation

Discussion

Turner syndrome (TS) is a genetic disorder characterized by the absence of one X chromosome in females. In contrast, Isochromosome Mosaic Turner Syndrome (IMTS) represents a distinct form with genetically different cell lineages. The case involves an eight-year-old female who presented with seizures, bilateral hand weakness, and an abnormal gait. The neurologic evaluation revealed an EEG showing sharp and slow waves, along with left-sided delta activity, leading to a diagnosis of generalized epilepsy. Genetic testing followed, showing the karyotype - 45,X,t(17;20)(q23;p13)/46,X,I(X)(q10),t(17;20)(q23;p13), consistent with IMTS. This rare case highlights a potential association between IMTS and epilepsy, emphasizing the importance of a multidisciplinary approach in evaluating TS patients. • Turner syndrome (TS): Complete or partial loss of one X chromosome in females. o Incidence rate: 1 in 2000 to 1 in 3000 live female births. • Various TS karyotypes reported; common ones include 45,X and mosaic TS variants like 45,X/46,X iso (Xq). o Diverse clinical manifestations: Short stature, cardiac anomalies, renal abnormalities, audiologic abnormalities, reproductive dysfunction. • Isochromosome Mosaic Turner Syndrome (IMTS): Variant with cells having differing karyotypes. o Prevalence: 8-9% in females with TS. o Patient's karyotype indicates a variant IMTS due to a chromosomal translocation. o IMTS with epilepsy not identified in existing literature even without chromosomal translocation. Introduction

Infancy and Childhood : • Acid reflux, food aversions, texture sensitivities, poor swallowing. • Mild developmental delay (see figure 1), ADHD, and extremity clumsiness • Focal seizure at age seven; occurred two weeks after starting Focalin® XR for ADHD.

Epilepsy in Turner Syndrome (TS) : • TS incidence: ~1 in 2500 live female births; prevalence uncertain due to undiagnosed milder phenotypes. • Epilepsy prevalence: ~1% in the general population; coexists in about 3% of TS cases. Comparison with Previous Cases : • Infrequent coexistence of TS and epilepsy. • Use of LTG and valproic acid (VPA) in previous case; balancing efficacy with long-term effects challenging (see Akasaka et al.'s case with mosaic TS and intractable epilepsy). Management Approach in Present Case : • LTG monotherapy for a few years; zonisamide introduced as adjunctive treatment. • Consideration of long-term adverse effects of VPA, particularly on cognitive function. • LTG's positive effect on pediatric epilepsy with ADHD symptoms aligns with patient's history. • Zonisamide as adjunct therapy known for effectiveness and tolerability in pediatric patients. Considerations in Drug Interactions : • Patients with TS may require hormone replacement therapy; potential interactions with antiepileptic drugs (CYP3A4 inducers). • Importance of individualized treatment approaches; absence of a predefined intervention protocol. Complexity of TS Cases and Limited Research : • Complexity in caring for TS patients; limited availability of researched treatment regimens for complex cases. • Need for further research to explore potential benefits and challenges of specific drug combinations in such cases.

Figure 1: Patients growth chart Onset of seizure disorder : • Age eight: Emergency room presentation with generalized tonic clonic seizure. • 24-hour amplitude-integrated EEG: Generalized sharp and slow waves (Figure 2), left-sided delta activity (Figure 3). • Diagnosed with epilepsy featuring both generalized and focal features.

Figure 3: EEG with Left Hemispheric Slowing

Figure 2: EEG reveals an abnormal pattern characterized by generalized epileptiform discharges, specifically bursts of 3-4 Hz spike and wave activity

Management and Follow up : • Initial treatment with levetiracetam ineffective; lamotrigine (LTG) resulted in decreased tonic-clonic seizures. • Zonisamide added; LTG dosage adjusted to control convulsions. • Ongoing follow-up includes monitoring cognitive development, educational progress, and medication adjustments. • Cardiovascular evaluation included normal electrocardiogram and echocardiogram. • Regular neuropsychological evaluations to assess cognitive function. Genetic Testing and Karyotype : • Continued muscle weakness and fatigue prompted genetic testing • Whole exome sequencing and mitochondrial sequencing at age nine. • Results: TS variant, balanced translocation between chromosomes 17 and 20. • Karyotype: 45,X,t(17;20)(q23;p13)/46,X,I(X)(q10),t(17;20)(q23;p13)

• The unique nature of epilepsy in TS patients requires individualized treatment approaches. • Call for further research to address the complexities of TS cases and explore effective treatment regimens.

References

Prugue C, Tjiattas-Saleski L, Enkemann S (December 22, 2023) Isochromosome Mosaic Turner Syndrome With Epilepsy and Developmental Abnormalities: A Case Report. Cureus 15(12): e50961. doi:10.7759/cureus.50961

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2024 Research Recognition Day