2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-SCANs not Separate Autosomal Recessive Spinocerebellar Ataxia group? - Toddler with Homozygous Novel Variants for SCAR2, SCAR23 and Axonal Neuropathy

SCANs not Separate Autosomal Recessive Spinocerebellar Ataxia group? - Toddler with Homozygous Novel Variants for SCAR2, SCAR23 and Axonal Neuropathy

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This document discusses the case of an 18-month-old male child who presented with developmental delay, viral upper respiratory infection, and developmental regression. The child had physical characteristics such as telecanthus, broad forehead, depressed nasal bridge, open mouth, and micrognathia. Investigations revealed normal results for brainstem evoked response audiometry (BERA) and electroencephalogram (EEG), but nerve conduction velocity showed bilateral axonal peroneal neuropathy. The child was found to have homozygous mutations in genes associated with autosomal recessive spinocerebellar ataxias (SCAR2 and SCAR23) but no variants in genes related to spinocerebellar ataxia with axonal neuropathy (SCAN).<br /><br />The authors suggest that SCAN may not be a separate group of autosomal recessive spinocerebellar ataxias and may require regrouping or a change in nomenclature. They highlight that axonal peripheral neuropathy and oculomotor apraxia, which are features of SCAN, have not been described in SCAR2 or SCAR23. Additionally, dystonia is described in SCAN2 but not in SCAR2 or SCAR23. However, the child in this case exhibited all three clinical features but had no variants in genes associated with SCAN.<br /><br />The progression of the child's illness showed a decrease in developmental quotient scores in gross motor, fine motor, and language domains. Parental Sanger sequencing revealed that both parents were heterozygous for the same mutations but were asymptomatic.<br /><br />In conclusion, this case raises questions about the classification and grouping of autosomal recessive spinocerebellar ataxias with axonal neuropathy. The presence of clinical features associated with SCAN in a patient without variants in genes related to SCAN suggests the need for further research and potentially a reevaluation of the current classification system.

Asset Subtitle

Presenting Author - Reena Gulati, MD, DM; Co-Author - Abishek Selvam, MBBS; Co-Author - Ranjithkumar Venkatraman, MD;

Meta Tag

Exome sequencing

Genotype-Phenotype Correlations

Inheritance Patterns

Intellectual disability

Neuroscience

Phenotypic delineation of disorders

Sequencing

Variant Detection

Co-Author Abishek Selvam, MBBS

Co-Author Ranjithkumar Venkatraman, MD

Presenting Author Reena Gulati, MD, DM

Keywords

developmental delay

viral upper respiratory infection

telecanthus

bilateral axonal peroneal neuropathy

SCAR2

SCAR23

spinocerebellar ataxia with axonal neuropathy

SCAN

dystonia

classification