CASE REPORT article
Front. Med.
Sec. Precision Medicine
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1623593
This article is part of the Research TopicNew Insights into Precision Medicine: Artificial Intelligence and GenomicsView all articles
The widening genetic and phenotypic spectrum of ultra-rare PDE4Drelated acroscyphodysplasia
Provisionally accepted
- 1Research Centre for Medical Genetics, Moscow, Russia
- 2H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
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Acroscyphodysplasia (ASD) is an ultra-rare skeletal dysplasia characterized by severe brachydactyly, metaphyseal scaphoid knee deformities, growth retardation and intellectual disability.To date, only seven cases of ASD have been reported, associated with missense variants in the PDE4D gene. We report a 7-year-old girl with ASD features including midface hypoplasia, severe growth retardation (-4.81 SDS height), progressive postnatal development of "cup-shaped" knee metaphyses, and unilateral humeral bowing, demonstrating mosaic growth plate involvement. Whole genome sequencing revealed a novel PDE4D missense variant (c.934C>T, p.Leu312Phe) in the UCR2 autoinhibitory domain, distinct from known acrodysostosis-associated variants. Expanding clinical, radiological characteristics and nutation spectrum of PDE4D-related ASD is highly important for understanding syndrome variability, aiding in earlier detection and more accurate recurrence risk assessment.
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Received: 06 May 2025; Accepted: 23 Jul 2025.
Copyright: © 2025 Morgul, Sharova, Kenis, Orlova, Ryzhkova and Markova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Margarita Sharova, Research Centre for Medical Genetics, Moscow, Russia
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