Neuropediatrics 2021; 52(02): 098-104
DOI: 10.1055/s-0040-1715629
Original Article

Clinical Characteristics and Genotype–Phenotype Correlation in Children with KMT2E Gene-Related Neurodevelopmental Disorders: Report of Two New Cases and Review of Published Literature

Indar Kumar Sharawat*
1  Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Prateek Kumar Panda*
1  Division of Pediatric Neurology, Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India
,
Lesa Dawman*
2  Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
› Author Affiliations
Funding None.

Abstract

Background In recent years, many new candidate genes are being identified as putative pathogenic factors in children with developmental delay and autism. Recently, heterozygous mutations in the KMT2E gene have been identified as a cause of a unique neurodevelopmental disorder with variable combination of global developmental delay or isolated speech delay, intellectual disability, autistic features, and seizures.

Methods Here, we present two new cases of KMT2E mutation-associated neurodevelopmental disorder in a 4-year-old girl and 5-year-old boy. We also performed a pooled review of the previously published cases of KMT2E-related neurodevelopmental disorder. Articles were identified through search engines using appropriate search terms.

Results Along with the presented 2 cases, 40 cases were analyzed. Out of them, 30, 6, and 4 children had protein-truncating mutations, missense mutations, and copy number variants, respectively. The common features were global developmental delay (97%) followed by macrocephaly (35%), seizures (30%), and autism (25%). Children with missense variants had severe phenotype, with microcephaly, profound developmental delay, and increased frequency of seizures. Neuroimaging revealed nonspecific changes, including cerebral white matter signal abnormalities.

ConclusionKMT2E-related neurodevelopmental disorder remains one of the clinical differentials in children with global developmental delay and/or autistic features/seizure. With the reporting of more cases in the future, the already heterogeneous clinical spectrum of this disease is likely to be widened.

Disclaimers

Nil.


* All the authors contributed equally and share joint first authorship.


Supplementary Material



Publication History

Received: 15 April 2020

Accepted: 22 June 2020

Publication Date:
27 October 2020 (online)

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