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1127 - Hyperekplexia secondary to rare biallelic mutation of SLC6A5: A case report

Thursday, February 27, 2025

5:00 PM - 6:30 PM MST

Presenting Author(s)

GG

Giorgina Giampaolo, MD

Resident
Montefiore Medical Center, Bronx, NY/Albert Einstein College of Medicine, Bronx, NY
New York, New York, United States

Co-Author(s)

SI

Sarah Ibrahim, BA

Medical Student
Montefiore Medical Center, Bronx, NY/Albert Einstein College of Medicine, Bronx, NY
Bronx, New York, United States
JL

Joshua B. Lewis, MD, PhD

Resident
Montefiore Medical Center, Bronx, NY/Albert Einstein College of Medicine, Bronx, NY
Bronx, New York, United States
Dona C. Kathirithamby, MD

Attending
Montefiore Medical Center, Bronx, NY/Albert Einstein College of Medicine, Bronx, NY
Bronx, New York, United States

Case Diagnosis: Hyperekplexia secondary to rare biallelic mutation of SLC6A5

Case Description: An 18-month-old female presented to pediatric rehabilitation clinic with concern for decreased speech, history of seizure-like episodes, walking apprehension, and gross motor delays. A grossly normal chromosome analysis was performed before birth as the patient's parents were consanguineous. Her birth was complicated by apneic episodes, generalized stiffness, and EEG findings concerning for seizure activity. Follow-up genetic screening demonstrated a biallelic expression of the SCL6A5 gene, a rare but known cause of hyperekplexia or “human startle disease”. Physical exam was remarkable for axial hypotonia, wide-based gait with decreased balance and coordination, and hyperlordosis of her spine while standing. The patient never crawled but transitioned from sitting and moving on her buttocks to cruising with support. Given these deficits, she was referred for physical and occupational therapy for improvement in gross motor skills, gait training, strength training, and bilateral ankle foot orthoses to improve ankle alignment.

Discussions: Hyperekplexia is characterized early in infancy by exaggerated myoclonic startle reactions and periods of generalized stiffness often resulting in falls. Patients with SLC6A5 variants have life-threatening risks including neonatal apnea and breath-holding spells. These symptoms can result in apprehension and avoidance behaviors that may manifest as developmental delays. This case highlights the importance of sequential progression through motor development stages. Our patient’s difficulty crawling may have decreased her core strength and truncal support, further exacerbating the child’s apprehension resulting in an inability to walk unsupported. Additionally, this gait instability may trigger myoclonic startle reactions and apneic episodes.

Conclusions: Hyperekplexia is a rare neurological disorder that results in myoclonic stiffness and apneic episodes. Patients may demonstrate developmental delays which may exacerbate their symptoms in a feedback loop. Although much is unknown about this disease's progression, pediatric physiatrists play a significant role in intervening to improve developmental and functional outcomes.