Further delineation of HIDEA syndrome.
HIDEA syndrome
P4HTM
developmental delay
hypoventilation
intellectual disability
reverse phenotyping
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
10
04
2020
revised:
23
08
2020
accepted:
27
08
2020
pubmed:
24
9
2020
medline:
25
6
2021
entrez:
23
9
2020
Statut:
ppublish
Résumé
Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in P4HTM, which encodes an atypical member of the prolyl 4-hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole-exome sequencing (WES) revealed novel disease-causing variants in P4HTM. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment/developmental delay, and hypotonia, which seem to be consistent findings. One patient only presented with hypotonia, developmental delay, and abnormal eye movements, which highlights the challenge in diagnosing milder cases with this new syndrome. Other notable features include mild facial dysmorphism, obesity, and brain dysmyelination and atrophy. We conclude that HIDEA is a highly variable syndrome and suspect that a large fraction of patients will be diagnosed via reverse phenotyping after recessive P4HTM variants are identified by agnostic genomic sequencing assays.
Identifiants
pubmed: 32965080
doi: 10.1002/ajmg.a.61885
doi:
Substances chimiques
Prolyl Hydroxylases
EC 1.14.11.-
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2999-3006Informations de copyright
© 2020 Wiley Periodicals LLC.
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