Objective: To report a novel genetic mutation in the SLC9A1 gene presenting with childhood onset ataxia and sensorineural hearing loss.

Background: Lichtenstein-Knorr syndrome is a juvenile onset form of cerebellar ataxia and sensorineural hearing loss, first described in 1930 [1]. The association of the SLC9A1 gene with this syndrome was first identified in 2014 by demonstration of a loss of function missense mutation in exon 3 of the SLC9A1 gene which codes for the Na+/H+ exchanger isoform one (NHE1), a plasma membrane protein expressed in human cells [2].   In this study, three siblings born to first-degree consanguineous parents of Turkish origin were affected with cerebellar ataxia and deafness [2]. After this initial report, two new homozygous mutations were reported in two brothers born in a non-consanguineous Chinese family with cerebellar ataxia (deletion mutation in exon 1 of SLC9A1) [3] and an Indian boy, born out of consanguineous marriage with cerebellar ataxia, deafness, and seizure (non-sense mutation in exon 6 of the SLC9A1 gene) [4].

Method: Case report

Results: A 19-year-old female with non-consanguineous parents of Mexican origin and a history of developmental delay and learning disabilities presented with childhood onset difficulty walking, sensorineural hearing loss and seizure like events describes as blacking out episodes preceded by dizziness and stomachache, and at least one generalized convulsion. On examination, she was noted to have scanning speech, impaired saccades, dysmetria, dysdiadochokinesia and cerebellar ataxia. Further history revealed a similar presentation in her younger sister. Genetic testing was pursued which was significant for a homozygous mutation with partial deletion in exon 2 of the SLC9A1 gene. The patient’s mother was heterozygous for the mutation. Her father’s sample was not available.

Conclusion: To date, a recessive SLC9A1 related pathogenic variant causing Lichtenstein-Knorr syndrome has been reported in six cases. This is the seventh case with a novel mutation in the SCL9A1 gene. The phenotype of our case was very similar to the cases reported by Guissart et al and Hesarur et al with cerebellar ataxia and profound deafness. This case serves as a building block to our limited knowledge about the various genotypic variants and their phenotypic expressions in this syndrome.

References: 1. Lichtenstein, H., & Knorr, A. (1930). Über einige Fälle von fortschreitender Schwerhörigkeit bei hereditärer Ataxie. Deutsche Zeitschrift für Nervenheilkunde, 114, 1-28.
2. Guissart, C., Li, X., Leheup, B., Drouot, N., Montaut-Verient, B., Raffo, E., … & Koenig, M. (2015). Mutation of SLC9A1, encoding the major Na+/H+ exchanger, causes ataxia–deafness Lichtenstein–Knorr syndrome. Human molecular genetics, 24(2), 463-470.
3. Iwama, K., Osaka, H., Ikeda, T., Mitsuhashi, S., Miyatake, S., Takata, A., … & Matsumoto, N. (2018). A novel SLC9A1 mutation causes cerebellar ataxia. Journal of human genetics, 63(10), 1049-1054.
4. Hesarur, N., Bardhan, M., Taallapalli, A., Nashi, S., Udupi, G. A., & Kulkarni, G. B. (2022). Lichtenstein–Knorr syndrome: A rare case of ataxia with sensorineural hearing loss. Annals of Indian Academy of Neurology, 25(5), 970-973.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-slc9a1-mutation-associated-with-cerebellar-ataxia-and-sensorineural-hearing-loss/