Abstract Details

Title Variants in PNPLA8 are Associated with Developmental Epileptic Encephalopathy and Cerebellar Atrophy.

Topic Child Neurology and Developmental Neurology

Presentation(s) P6 - Poster Session 6 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-002

Background This novel likely pathogenic variant in PNPLA8 (c.2227 c>T, p. Q743*), encodes for mitochondrial independent calcium phospholipase A2 gamma, which catalyzes the cleavage of fatty acids from membrane phospholipids. This gene has a role in maintaining lipid membrane homeostasis of the peroxisomes and mitochondria. Review of the literature described two phenotypes associated with this gene thus far, one is intractable neonatal epilepsy with microcephaly and cerebellar atrophy. The other presentation is mitochondrial myopathy with developmental regression and epilepsy

Objective To describe a novel homozygous likely pathogenic variant in the PNPLA8 gene (c.2227 c>T, p. Q743*) associated with developmental epileptic encephalopathy and cerebellar atrophy in two siblings.

Design/Methods N/A

Results The proband is a late preterm (34 weeks) baby with oligohydramnios in-utero, intrauterine growth restriction, microcephaly, and status epilepticus. Seizures began within minutes of birth and were characterized by tonic and myoclonic seizures, apnea and high pitch noises. The EEG showed burst suppression pattern and multifocal seizures refractory to multiple anti-seizure medications and vitamins/cofactors including pyridoxine, folinic acid, pyridoxal-5-phosphate, and biotin. Urine organic acids showed mildly elevated lactate, pyruvate, succinic and adipic acids. Plasma lactate, amino acids and acylcarnitine profiles were essentially normal. MRI demonstrated cerebellar atrophy and immature sulcation pattern. The proband’s brother (born at 30 weeks) passed away after a similar presentation of developmental epileptic encephalopathy, cerebellar atrophy and elevated urine organic acids. Clinical rapid exome sequencing identified a novel PNPLA8 (c.2227 c>T, p. Q743) likely pathogenic variant that was retrospectively found in the affected sibling as well.

Conclusions Likely pathogenic variants in the PNPLA8 gene appear to be causative of the developmental epileptic encephalopathy that encompasses both myoclonic epilepsy of infancy and Ohtahara Syndrome.

Authors/Disclosures
Cheryl Fields, DO (Childrens Specialized Hospital) PRESENTER	Dr. Fields has nothing to disclose.
Elissa Yozawitz, MD	Dr. Yozawitz has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Nagma Dalvi, MD (Montefiore Medical Center)	Dr. Dalvi has nothing to disclose.
Leslie D. Delfiner, MD (Montefiore Medical Center)	Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapies. Dr. Delfiner has received personal compensation in the range of $500-$4,999 for serving as a MDA Engage Event Chair and speaker with Muscular Dystrophy Association.
Donya Eizadkhah, MD (Montefiore)	Dr. Eizadkhah has nothing to disclose.
Solomon L. Moshe, MD, FAAN	Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Moshe has received publishing royalties from a publication relating to health care. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as a Reviewer of study sections with NINDS.
	No disclosure on file
Kimberly O'Neill, MD	Dr. O'Neill has nothing to disclose.
Aparna Polavarapu Ramarao, MD (Montefiore Medical Center)	Dr. Polavarapu Ramarao has nothing to disclose.
	No disclosure on file
Apirada Thongsing, MD (Kapiolani)	Dr. Thongsing has nothing to disclose.
Solomon L. Moshe, MD, FAAN	Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Moshe has received publishing royalties from a publication relating to health care. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as a Reviewer of study sections with NINDS.