Infantile neuroaxonal dystrophy in a pair of Malaysian siblings with progressive cerebellar atrophy: Description of an expanded phenotype with novel PLA2A6 variants

Limin Li, Choong Yi Fong, Chee Geap Tay, Sok Kun Tae, Hisato Suzuki, Kenjiro Kosaki, Meow Keong Thong

Research output: Contribution to journalArticle

Abstract

Infantile neuroaxonal dystrophy 1 (INAD) (OMIM #256600) is a rare infantile onset neurodegenerative disease characterised by neuroregression and hypotonia, evolving into generalized spasticity, blindness and dementia. We report our diagnostic approach of a pair of siblings with psychomotor regression, hypotonia, optic atrophy and auditory neuropathy. The brain magnetic resonance imaging (MRI) showed progressive cerebellar atrophy. Genetic testing of the PLA2G6 confirmed presence of compound heterozygous novel mutations. As the variant c. 196C>T (p.Gln66X) was a truncating variant, it was considered as pathogenic while the variant c. 2249G>A (p. Cys750Tyr) was considered as “likely pathogenic” by bioinformatics analyses. Our patient expands the clinical phenotype of INAD as it described the first South-East Asian patient with INAD-associated auditory neuropathy. Our report highlights the importance of increased awareness of this condition amongst clinicians, the use of deep phenotyping using neuroimaging and the clinical utility of gene sequencing test in the delineation of syndromes associated with infantile neurodegenerative disease.

Original languageEnglish
JournalJournal of Clinical Neuroscience
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Neuroaxonal Dystrophies
Atrophy
Siblings
Muscle Hypotonia
Phenotype
Neurodegenerative Diseases
Genetic Databases
Optic Atrophy
Optic Nerve Diseases
Genetic Testing
Blindness
Computational Biology
Neuroimaging
Dementia
Magnetic Resonance Imaging
Mutation
Brain
Genes
Auditory neuropathy

Keywords

  • Auditory neuropathy
  • Cerebellar atrophy
  • Infantile neuroaxonal dystrophy
  • Novel mutation

ASJC Scopus subject areas

  • Surgery
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Infantile neuroaxonal dystrophy in a pair of Malaysian siblings with progressive cerebellar atrophy : Description of an expanded phenotype with novel PLA2A6 variants. / Li, Limin; Fong, Choong Yi; Tay, Chee Geap; Tae, Sok Kun; Suzuki, Hisato; Kosaki, Kenjiro; Thong, Meow Keong.

In: Journal of Clinical Neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

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