ROSAH syndrome mimicking chronic uveitis

To suggest a unique missense variant candidate based on long‐term ophthalmological changes and associated systemic signs described in five patients from two unrelated families affected by an autosomal dominant multi‐systemic disorder including Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anh...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical genetics Vol. 103; no. 4; pp. 453 - 458
Main Authors:	Fardeau, Christine, Alafaleq, Munirah, Dhaenens, Claire‐Marie, Dollfus, Hélène, Koné‐Paut, Isabelle, Grunewald, Olivier, Morel, Jean‐Baptiste, Titah, Cherif, Saadoun, David, Lazeran, Patrice Olivier, Meunier, Isabelle
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-04-2023 Wiley
Subjects:	alpha‐protein kinase 1 cone‐rod dystrophy DNA Mutational Analysis Edema Follow-Up Studies Genetic analysis Genetic screening Genomes Headache Hereditary diseases Humans Hypohidrosis Life Sciences macular oedema Migraine Morbidity Next-generation sequencing Optic nerve Optic Nerve Diseases papillary oedema Patients Pedigree Phenotype Phenotypes Retinal degeneration retinal dystrophy ROSAH syndrome Splenomegaly Syndrome Uveitis retinal dystrophy macular oedema alpha-protein kinase 1 cone-rod dystrophy ROSAH syndrome uveitis papillary oedema macular edema papillar edema pseudouveitis
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	To suggest a unique missense variant candidate based on long‐term ophthalmological changes and associated systemic signs described in five patients from two unrelated families affected by an autosomal dominant multi‐systemic disorder including Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and migraine Headaches, called ROSAH syndrome, related to a unique missense variant in ALPK1 gene. Observational longitudinal follow‐up study of unrelated families. Clinical analysis of ophthalmological and systemic examinations was performed, followed by genetic analysis, including targeted Next Generation Sequencing (NGS) and Whole‐Genome Sequencing (WGS). The ophthalmological phenotype showed extensive optic nerve swelling associated with early macular oedema and vascular leakage. The main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis and hypersegmented polynuclear cells. WGS, shortened in the second family by the gene candidate suggestion, revealed in all patients the heterozygous missense variant c.710C>T; p.(Thr237Met) in ALPK1. The primary morbidity in ROSAH syndrome in this cohort appeared ophthalmological. Comprehensive, detailed phenotype changes aided by the advancement in genetic testing could allow an early genetic diagnosis of ROSAH syndrome and targeted treatment. The unique missense variant may be suggested as a target of gene correction therapy. An autosomal dominant multi‐systemic disorder including Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and migraine Headaches, called ROSAH syndrome, has been related to a unique missense variant in ALPK1 gene. The main morbidity is ophthalmological and most of the patients have been treated for years with immunosuppressive treatments for a chronic bilateral posterior uveitis, without significant ophthalmological benefit. The initial ophthalmological phenotype showed extensive optic nerve swelling‐associated with early macular oedema and vascular leakage. Main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis and hypersegmented polynuclear cells. Ten years later significant visual loss occurred linked to change towards a centromacular atrophy. NGS panels including main genes known to be associated with autosomal dominant inherited Retinal dystrophies were unsuccessful. WGS shortened if candidate gene was suggested, allows diagnosis and adequate familial medical care.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0009-9163 1399-0004
DOI:	10.1111/cge.14286