An Extremely Rare Case of Birk-Barel Syndrome With Severe Central Apneas

Abymael Frontanes-Heredia,Sherry L Santiago-Castro,Wilfredo De Jesús-Rojas,Wilmarie J Bruckman-Blanco,Michael A Ramirez-Arenalde

doi:10.7759/cureus.15862

Abstract

Birk-Barel syndrome, alternatively known as KCNK9 imprinting syndrome, is caused by a missense mutation in the potassium two pore domain channel subfamily K member 9 (KCNK9) gene on chromosome 8q24.3. This syndrome demonstrates dominant inheritance and is imprinted with paternal silencing, where the paternally inherited allele is silenced, and the maternally inherited allele is active. Congenital hypotonia, palatal abnormalities, intellectual disability, severe feeding difficulties, and dysmorphic facial features characterize this sporadic genetic syndrome. To date, there are approximately 21 molecularly diagnosed individuals worldwide described in the literature. We describe the first known case of Puerto Rican ethnicity, a 16-month-old female born prematurely at 36-weeks with Birk-Barel syndrome, confirmed with whole-exome sequencing, and her response to non-invasive ventilation as a treatment for her sleep breathing disorder.

Highlights

Birk-Barel syndrome, known as KCNK9 imprinting syndrome, was first described in 2008 by Barel et al [1]. This syndrome demonstrates autosomal dominant inheritance with paternal imprinting. It is caused by a specific missense mutation 770G>A in exon 2, replacing glycine at position 236 by arginine (G236R) in the maternal copy of KCNK9 within this locus [2]
We describe the first case of Birk-Barel syndrome of Puerto Rican ethnicity and her response to non-invasive ventilation as a treatment for her central apneas
A novel variant c.710 > A: p.Ala237Asp in the KCNK9 gene and mosaicism 46,XY,r(8)(p23q24.3)/45, XY,−8 have been reported in a 17-year-old girl and a 2.5-yearold boy, respectively [5,6]

Summary

Introduction

Birk-Barel syndrome, known as KCNK9 imprinting syndrome, was first described in 2008 by Barel et al [1]. This syndrome demonstrates autosomal dominant inheritance with paternal imprinting. KCNK9 encodes a two pore-domain leak potassium channel TASK3, which regulates the resting membrane potential and influences action potential duration and neuron firing frequency [3]. These channels are found in higher concentrations in neurons, especially neurons of the cerebellum. TASK3 channels modulate the excitability of cells and play an essential role during the development of the central nervous system [3]

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Discussion

Conclusion