Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease
IntroductionVanishing White Matter disease (VWM) is a rare neurological disease, with an autosomal recessive inheritance. In this case report, we describe two four-year-old dizygotic twin brothers diagnosed with VWM with the same genotype and different phenotypes. We also describe a new likely patho...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Pediatrics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2025.1643040/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849242870221897728 |
|---|---|
| author | Ellis Oron-Lexner Bjørk Ditlev Larsen Maria Therese Schelde-Olesen |
| author_facet | Ellis Oron-Lexner Bjørk Ditlev Larsen Maria Therese Schelde-Olesen |
| author_sort | Ellis Oron-Lexner |
| collection | DOAJ |
| description | IntroductionVanishing White Matter disease (VWM) is a rare neurological disease, with an autosomal recessive inheritance. In this case report, we describe two four-year-old dizygotic twin brothers diagnosed with VWM with the same genotype and different phenotypes. We also describe a new likely pathogenic variant leading to VWM.MethodClinical examination, radiologic analysis and genetic workups, including whole genome sequencing and trio-genome analysis were conducted to diagnose and describe the patients' disease.ResultsA four-year-old boy was hospitalized with acute loss of motor functions and a somnolent state after a minor head trauma. Based on the clinical evaluation, radiological findings and genetic analysis he was diagnosed with VWM. The proband's twin carried identical pathogenic variants and exhibited white matter lesions on MRI. However, unlike the proband who presented with non-specific symptoms since the age of one, his twin remained asymptomatic at diagnosis.DiscussionThis case may indicate that factors other than genotype could affect the age of onset of VWM. During the genetic analysis a previously unknown genetic variant was detected, which is now classified as a likely pathogenic variant of VWM. |
| format | Article |
| id | doaj-art-9de798dec21a4e0f89596e0f8a026341 |
| institution | Kabale University |
| issn | 2296-2360 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj-art-9de798dec21a4e0f89596e0f8a0263412025-08-20T03:59:40ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-08-011310.3389/fped.2025.16430401643040Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter diseaseEllis Oron-Lexner0Bjørk Ditlev Larsen1Maria Therese Schelde-Olesen2Department of Pediatrics and Adolescent Medicine, Sygehus Sønderjylland, Aabenraa, DenmarkDepartment of Clinical Genetics, Odense Universitetshospital, Odense, DenmarkDepartment of Clinical Genetics, Odense Universitetshospital, Odense, DenmarkIntroductionVanishing White Matter disease (VWM) is a rare neurological disease, with an autosomal recessive inheritance. In this case report, we describe two four-year-old dizygotic twin brothers diagnosed with VWM with the same genotype and different phenotypes. We also describe a new likely pathogenic variant leading to VWM.MethodClinical examination, radiologic analysis and genetic workups, including whole genome sequencing and trio-genome analysis were conducted to diagnose and describe the patients' disease.ResultsA four-year-old boy was hospitalized with acute loss of motor functions and a somnolent state after a minor head trauma. Based on the clinical evaluation, radiological findings and genetic analysis he was diagnosed with VWM. The proband's twin carried identical pathogenic variants and exhibited white matter lesions on MRI. However, unlike the proband who presented with non-specific symptoms since the age of one, his twin remained asymptomatic at diagnosis.DiscussionThis case may indicate that factors other than genotype could affect the age of onset of VWM. During the genetic analysis a previously unknown genetic variant was detected, which is now classified as a likely pathogenic variant of VWM.https://www.frontiersin.org/articles/10.3389/fped.2025.1643040/fullVanishing White Matter diseaseCACH VWM syndromeeukaryotic initiation factor-2Bleukoencephalopathycase reportphenotype |
| spellingShingle | Ellis Oron-Lexner Bjørk Ditlev Larsen Maria Therese Schelde-Olesen Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease Frontiers in Pediatrics Vanishing White Matter disease CACH VWM syndrome eukaryotic initiation factor-2B leukoencephalopathy case report phenotype |
| title | Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease |
| title_full | Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease |
| title_fullStr | Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease |
| title_full_unstemmed | Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease |
| title_short | Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease |
| title_sort | case report new genetic variant and widely different phenotypes observed in twins with vanishing white matter disease |
| topic | Vanishing White Matter disease CACH VWM syndrome eukaryotic initiation factor-2B leukoencephalopathy case report phenotype |
| url | https://www.frontiersin.org/articles/10.3389/fped.2025.1643040/full |
| work_keys_str_mv | AT ellisoronlexner casereportnewgeneticvariantandwidelydifferentphenotypesobservedintwinswithvanishingwhitematterdisease AT bjørkditlevlarsen casereportnewgeneticvariantandwidelydifferentphenotypesobservedintwinswithvanishingwhitematterdisease AT mariatheresescheldeolesen casereportnewgeneticvariantandwidelydifferentphenotypesobservedintwinswithvanishingwhitematterdisease |