Lethal respiratory course and additional features expand the phenotypic spectrum of PIEZO2‐related distal arthrogryposis type 5

Distal arthrogryposes (DA) are a group of conditions presenting with multiple congenital contractures in the distal joints. The 10 types of DA are distinguished by different extra‐articular manifestations. Heterozygous gain‐of‐function variants in PIEZO2 are known to cause a spectrum of DA condition...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2023-02, Vol.191 (2), p.546-553
Main Authors: Oliwa, Agata, Hendson, Glenda, Longman, Cheryl, Synnes, Anne, Seath, Kim, Barnicoat, Angela, Hall, Judith G., Patel, Millan S.
Format: Article
Language:English
Subjects:
Arthrogryposis
Arthrogryposis - diagnosis
Arthrogryposis - genetics
Central nervous system
Cleft lip/palate
Humans
Ion Channels - genetics
lipid myopathy
mechanosensation
Myopathy
Pedigree
Phenotype
Phenotypes
PIEZO2
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Summary:Distal arthrogryposes (DA) are a group of conditions presenting with multiple congenital contractures in the distal joints. The 10 types of DA are distinguished by different extra‐articular manifestations. Heterozygous gain‐of‐function variants in PIEZO2 are known to cause a spectrum of DA conditions including DA type 3, DA type 5, and possibly Marden Walker syndrome, which are usually distinguished by the presence of cleft palate (DA3), ptosis and restriction in eye movements (DA5), and specific facial abnormalities and central nervous system involvement, respectively. We report on a boy with a recurrent de novo heterozygous PIEZO2 variant in exon 20 (NM_022068.3: c.2994G > A, p.(Met998Ile); NM_001378183.1: c.3069G > A, p.(Met1023Ile)), who presented at birth with DA and later developed respiratory insufficiency. His phenotype broadly fits the PIEZO2 phenotypic spectrum and potentially extends it with novel phenotypic features of pretibial linear vertical crease, immobile skin, immobile tongue, and lipid myopathy.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.63019