The Beneficence of Cuddle Therapy in Hyperekplexia: A Case Report.

BACKGROUND: Benevolent injustice occurs when well-intentioned treatment efforts produce an outcome that limits the potential of a patient. The unintended harm can result in significant moral distress for the family and the healthcare team. CLINICAL FINDINGS: We discussed an ethical dilemma regarding a neonate who had suspected seizure and hypoxic-ischemic encephalopathy after home birth delivery. The healthcare team experienced moral distress about the mother's desire to not use anti-seizure medications and instead trial other interventions such as cuddling. Subsequently, clinical analysis ruled out a seizure disorder. Genetic studies on this neonate confirmed hereditary hyperekplexia, which presented as exaggerated Moro reflex and apnea that mimicked seizure. INTERVENTION: We discussed how applying any one of the 4 basic ethical principles of autonomy, beneficence, nonmaleficence, or justice could counteract benevolent injustice and moral distress. OUTCOMES: Discussions with the patient's mother and nurse allowed the team to overcome their reluctance to try the mother's treatment recommendations. This resulted in adopting the seemingly counterintuitive intervention of cuddling that turned out to be effective for this neonate with hereditary hyperekplexia. PRACTICE RECOMMENDATIONS: The moral distress associated with benevolent injustice should be identified early to minimize long-term consequences to the patient, family, and healthcare team. Healthcare teams should learn to apply ethical principles when discussing patient care concerns in an unbiased manner. Guided ethical discussions allow us to be more efficient in providing family-centered care that aligns with the patient's best interest.

Novel mutations in SLC6A5 with benign course in hyperekplexia.

Infants suffering from life-threatening apnea, stridor, cyanosis, and increased muscle tone may often be misdiagnosed with infantile seizures and inappropriately treated because of lack and delay in genetic diagnosis. Here, we report a patient with increased muscle tone after birth and hypertonic attacks with life-threatening apnea but no epileptiform patterns in EEG recordings. We identified novel compound heterozygous variants in SLC6A5 (NM_004211.4:c.[1429T > C];[1430delC]) by trio whole-exome sequencing, containing a base deletion inherited by the asymptomatic mother leading to a frameshift (c.1430delC, p.Ser477PhefsTer9) and a de novo base exchange leading to an amino acid change (c.1429T > C, p.Ser477Pro). To date, there are four known disease-associated genes for primary hyperekplexia, all of which are involved in the functioning of glycinergic synapses. SLC6A5 encodes the sodium- and chloride-dependent glycine transporter 2 (GlyT2), which recaptures glycine, a major inhibitory transmitter in the brainstem and spinal cord. The diagnosis altered the patient's medical care to his benefit because SLC6A5 mutations with rather benign courses of hyperekplexia may be spared of needless pharmacotherapy. Symptoms eventually decreased in frequency until about once in 2 mo at 2 yr age. We present the first report of halting hyperekplexia episodes by maternal soothing in multiple instances. We highlight the importance of clarifying the genetic diagnosis by rapid next-generation sequencing techniques in this group of infantile apneic attacks with hyperekplexia due to the broad differential diagnoses.

Hyperekplexia: Report on phenotype and genotype of 16 Jordanian patients.

BACKGROUND: Hyperekplexia, is a rare disorder characterized by excessive startle response to acoustic, visual, or other stimuli. It is inherited in autosomal recessive and dominant pattern. OBJECTIVE: To describe the clinical and genetic features of hyperekplexia in Jordanian patients. METHODS: This retrospective study includes all patients with proved genetic diagnosis of hyperekplexia who presented to our clinic at the Jordan University Hospital from January 2001 through July 2015. RESULTS: A total of 16 children from 12 families were included. The total follow up period ranged from one to eleven years. The majority of the patients (13/16=81.3%) were initially misdiagnosed as epilepsy. All patients had excessive startle response since birth. Tonic-apneic spells occurred in 15/16=93.8% patients. Fourteen patients (45/16=87.5%) received clonazepam. Stopping clonazepam by three years of age failed in 11/14 (78.6%) due to reappearance of tonic-apneic spells (8/14=57.1%), recurrent falling (10/14=71.4%) or due to both reasons (5/14=35.7%). Delayed motor development occurred in 7/16 (43.8%), speech delay in 4/16 (25.0%), global developmental delay in 1/16 (6.3%), and autism spectrum disorder in 1/16 (6.3%) patient. The mode of inheritance is autosomal recessive in all 12/12 (100%) families. Mutations in GLRA1 gene was present in 9/16 (56.3%); the most common mutation was in p.G254D (4/9; 44.5%). Mutations in the GLRB gene was present in 4/16 (25.0%) patients and the SLC6A5 gene in 3/16 (18.8%) patients. CONCLUSION: The clinical presentation of hyperekplexia in Jordanian patients is manifested by tonic-apneic spells in all homozygous patients. The persistence of apneic spells and recurrent falls throughout childhood necessitate continuous treatment and surveillance.