Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report.

UNLABELLED

Variants in the () gene cause a diverse spectrum of phenotypes of neurodevelopmental disorders (NDD) in male patients. This article describes the role of genetic testing using whole-exome sequencing (WES) in detecting a novel de novo frameshift variant in the gene in a female patient with autism, seizure, and global developmental delay.

CASE PRESENTATION

A 2-year-old girl with frequent seizures, global developmental delay, and autistic features was referred to our hospital. She was the second child of consanguineous non-affected parents. She had a high forehead, mildly prominent ears, and prominent nasal root. A generalized epileptiform discharge was noted in her electroencephalography. Brain MRI revealed corpus callosum agenesis, cerebral atrophy, and a left parafalcine cyst. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the gene, which creates a frameshift variant. The patient is on dual therapy of antiepilepsy drugs, physiotherapy, speech therapy, occupational therapy, and oral motor exercises.

CLINICAL DISCUSSION

Variants in the gene can result in various phenotypes in males transmitted from asymptomatic carrier females. However, several reports showed that the variants might cause phenotypes in females with milder symptoms than affected males.

CONCLUSION

We report a novel de novo ARX variant in an affected female with a NDD. Our study confirms that the variant might cause remarkable pleiotropy phenotypes in females. Moreover, WES could help to identify the pathogenic variant in NDD patients with diverse phenotypes.