Severe manifestation of Rauch-Azzarello syndrome associated with biallelic deletion of CTNND2

Pauly M, Krumbiegel M, Trumpp S, Braig S, Rupprecht T, Kraus C, Uebe S, Reis A, Vasileiou G (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Clinical Genetics Wiley-Blackwell

DOI: 10.1111/cge.14532

Abstract

CTNND2 encodes δ-catenin, a component of an adherens junction complex, and plays an important role in neuronal structure and function. To date, only heterozygous loss-of-function CTNND2 variants have been associated with mild neurodevelopmental delay and behavioral anomalies, a condition, which we named Rauch-Azzarello syndrome. Here, we report three siblings of a consanguineous family of Syrian descent with a homozygous deletion encompassing the last 19 exons of CTNND2 predicted to disrupt the transcript. All presented with severe neurodevelopmental delay with absent speech, profound motor delay, stereotypic behavior, microcephaly, short stature, muscular hypotonia with lower limb hypertonia, and variable eye anomalies. The parents and the fourth sibling were heterozygous carriers of the deletion and exhibited mild neurodevelopmental impairment resembling that of the previously described heterozygous individuals. The present study unveils a severe manifestation of CTNND2-associated Rauch-Azzarello syndrome attributed to biallelic loss-of-function aberrations, clinically distinct from the already described mild presentation of heterozygous individuals. Furthermore, we demonstrate novel clinical features in homozygous individuals that have not been reported in heterozygous cases to date.

Authors with CRIS profile

Melissa Pauly Institute of Human Genetics Mandy Krumbiegel Institute of Human Genetics Steffen Uebe Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Georgia Vasileiou Institute of Human Genetics

Involved external institutions

Klinikum Bayreuth DE Germany (DE)

How to cite

APA:

Pauly, M., Krumbiegel, M., Trumpp, S., Braig, S., Rupprecht, T., Kraus, C.,... Vasileiou, G. (2024). Severe manifestation of Rauch-Azzarello syndrome associated with biallelic deletion of CTNND2. Clinical Genetics. https://doi.org/10.1111/cge.14532

MLA:

Pauly, Melissa, et al. "Severe manifestation of Rauch-Azzarello syndrome associated with biallelic deletion of CTNND2." Clinical Genetics (2024).

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