Abstract Details

Title Genetic polyneuropathy in a teenage girl with pathogenic variants in TTR and WARS genes

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 078

Objective

To describe a pediatric patient presenting with neuropathy found to have pathogenic variants in TTR and WARS

Background Childhood neuropathies are predominantly genetic and present heterogeneously. Although hereditary ATTR is a well-known cause of neuropathy in adults, it is rare in children, and other genetic causes should be considered in pediatric patients with TTR mutations. Here we describe a pediatric patient with gait difficulty and pathogenic variants in TTR and WARS.

Design/Methods Case report

Results A 13 y/o AA female presented to neuromuscular clinic after developing progressive difficulty with ambulation at age 10. She was unable to pick up her feet, climb stairs, and experienced numbness/tingling in her extremities. On examination she had distal more than proximal weakness, absent tendon reflexes, and diminished pinprick sensation. She had a high steppage gait with impaired heel and toe walking. Motor nerve conductions showed reduced amplitudes. Concentric needle electrode examination revealed increased insertional activity and motor unit potentials had increased size and duration with variably reduced recruitment. SMN deletion testing was negative. Next generation neuropathy panel revealed a heterozygous variant in TTR (NM_000371.3) c.424G>A (p.Val142Ile). However, this variant is present in up to 3.9% of AA individuals and associated with adult onset cardiac features (hATTR-CM). This patient’s cardiac evaluation was normal. Given her young age of onset, trio whole exome sequencing was pursued and revealed a heterozygous likely pathogenic variant in WARS (NM_004184.3) c.413T>A (p.Phe138Tyr). The TTR and WARS variants were not detected in her mother; a sample from her father could not be obtained.

Conclusions

We describe pathogenic variants in the tryptophanyl aminoacyl tRNA synthetase gene (WARS) leading to distal hereditary motor neuropathy. This case highlights the possibility of secondary findings for adult-onset conditions such as TTR on routine genetic testing in children and the importance of counseling in the context of genetic testing.

Authors/Disclosures
Eleanor V. Thomas, MD, PhD (Emory University School of Medicine) PRESENTER	Dr. Thomas has nothing to disclose.
Rachel Logan	Rachel Logan has nothing to disclose.
	No disclosure on file
John L. Berk	John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis Pharmaceuticals. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca/IONIS. John L. Berk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eidos/BridgBio. John L. Berk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia Therapeutics. John L. Berk has received research support from Alnylam . John L. Berk has received research support from Ionis. John L. Berk has received research support from Eidos/Bridgbio.
Thomas Brannagan III, MD, F�鶹��ýӳ�� (Columbia University)	Dr. Brannagan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astra Zenica. Dr. Brannagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. The institution of Dr. Brannagan has received research support from Alnylam. The institution of Dr. Brannagan has received research support from Abcuro. The institution of Dr. Brannagan has received research support from Ionis. The institution of Dr. Brannagan has received research support from Vertex. The institution of Dr. Brannagan has received research support from NMD Pharma.
Sumit Verma, MD (Emory Children's Center)	Dr. Verma has nothing to disclose.

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