Confirmation of the Hotspot Variant in MAP3K20 Responsible for Deafness, Ectodermal Dysplasia, Craniosynostosis, Ectrodactyly, and Skeletal Anomaly Spectrum.

INTRODUCTION

Heterozygous variants in MAP3K20 have been implicated in a recently identified syndromic form of ectodermal dysplasia, distinguished by a unique combination of ectrodactyly, craniosynostosis, bilateral sensorineural hearing loss, and skeletal anomalies such as transverse limb defect, and brachydactyly.

CASE PRESENTATION: We present an 11-year-old male with ectrodactyly, ectodermal dysplasia, bilateral sensorineural hearing loss, and cutaneous syndactyly in both hands. A de novo heterozygous variant, c.837_839del p.(Asn279del), in MAP3K20 was identified in his whole exome sequencing.

CONCLUSION

The results of this study emphasize the critical role of MAP3K20 as a key gene in conditions involving ectrodactyly, craniosynostosis, bilateral sensorineural hearing loss, ectodermal features, transverse limb defect, and brachydactyly. We highlight the importance of prioritizing the recurrent p.(Asn279del) variant in genetic testing for affected individuals. Furthermore, we propose an acronym for this dominant disorder caused by the MAP3K20 gene variants: DECES (Dominant/Deafness, Ectodermal Dysplasia, Craniosynostosis, Ectrodactyly, Skeletal anomalies).