Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics
Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the FRMD7 gene. IIN poses a diagnostic challenge as underlying pre-symptomatic “multisystem” disord...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.977806/full |
| _version_ | 1818517026229977088 |
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| author | Nancy Aychoua Nancy Aychoua Elena Schiff Samantha Malka Vijay K Tailor Vijay K Tailor Hwei Wuen Chan Hwei Wuen Chan Hwei Wuen Chan Ngozi Oluonye Ngozi Oluonye Maria Theodorou Mariya Moosajee Mariya Moosajee Mariya Moosajee Mariya Moosajee |
| author_facet | Nancy Aychoua Nancy Aychoua Elena Schiff Samantha Malka Vijay K Tailor Vijay K Tailor Hwei Wuen Chan Hwei Wuen Chan Hwei Wuen Chan Ngozi Oluonye Ngozi Oluonye Maria Theodorou Mariya Moosajee Mariya Moosajee Mariya Moosajee Mariya Moosajee |
| author_sort | Nancy Aychoua |
| collection | DOAJ |
| description | Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the FRMD7 gene. IIN poses a diagnostic challenge as underlying pre-symptomatic “multisystem” disorders varying from benign to life-threatening should first be ruled out before nystagmus can be labeled as idiopathic. A multidisciplinary approach including multimodal ocular investigations and next-generation sequencing with whole-genome sequencing (WGS) or targeted gene panel testing is required to delineate the exact etiology. We report the clinical and genetic outcomes of 22 patients, from 22 unrelated families of diverse ethnicities, with IIN seen in the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between 2016 and 2022. Thirty-six percent (8/22) received a confirmed molecular diagnosis with eight mutations identified in two genes (seven in FRMD7 including one novel variant c.706_707del; p. [Lys236Alafs*66], and one in GPR143). This study expands the mutational spectrum of IIN and highlights the significant role of an integrated care pathway and broader panel testing in excluding underlying pathologies. |
| first_indexed | 2024-12-11T00:50:25Z |
| format | Article |
| id | doaj.art-c85d27dc85ec4ad68ea38909953a43df |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T00:50:25Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-c85d27dc85ec4ad68ea38909953a43df2022-12-22T01:26:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.977806977806Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnosticsNancy Aychoua0Nancy Aychoua1Elena Schiff2Samantha Malka3Vijay K Tailor4Vijay K Tailor5Hwei Wuen Chan6Hwei Wuen Chan7Hwei Wuen Chan8Ngozi Oluonye9Ngozi Oluonye10Maria Theodorou11Mariya Moosajee12Mariya Moosajee13Mariya Moosajee14Mariya Moosajee15Moorfields Eye Hospital NHS Foundation Trust, London, United KingdomInstitute of Ophthalmology, University College London, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomExperimental Psychology, University College London, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomInstitute of Ophthalmology, University College London, London, United KingdomDepartment of Ophthalmology, National University Hospital, Singapore, SingaporeMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomGreat Ormond Street Hospital for Children NHS Foundation Trust, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomMoorfields Eye Hospital NHS Foundation Trust, London, United KingdomInstitute of Ophthalmology, University College London, London, United KingdomGreat Ormond Street Hospital for Children NHS Foundation Trust, London, United KingdomThe Francis Crick Institute, London, United KingdomIdiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the FRMD7 gene. IIN poses a diagnostic challenge as underlying pre-symptomatic “multisystem” disorders varying from benign to life-threatening should first be ruled out before nystagmus can be labeled as idiopathic. A multidisciplinary approach including multimodal ocular investigations and next-generation sequencing with whole-genome sequencing (WGS) or targeted gene panel testing is required to delineate the exact etiology. We report the clinical and genetic outcomes of 22 patients, from 22 unrelated families of diverse ethnicities, with IIN seen in the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between 2016 and 2022. Thirty-six percent (8/22) received a confirmed molecular diagnosis with eight mutations identified in two genes (seven in FRMD7 including one novel variant c.706_707del; p. [Lys236Alafs*66], and one in GPR143). This study expands the mutational spectrum of IIN and highlights the significant role of an integrated care pathway and broader panel testing in excluding underlying pathologies.https://www.frontiersin.org/articles/10.3389/fgene.2022.977806/fullFRMD7 geneGPR143 genenystagmuswhole-genome sequencingalbinism |
| spellingShingle | Nancy Aychoua Nancy Aychoua Elena Schiff Samantha Malka Vijay K Tailor Vijay K Tailor Hwei Wuen Chan Hwei Wuen Chan Hwei Wuen Chan Ngozi Oluonye Ngozi Oluonye Maria Theodorou Mariya Moosajee Mariya Moosajee Mariya Moosajee Mariya Moosajee Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics Frontiers in Genetics FRMD7 gene GPR143 gene nystagmus whole-genome sequencing albinism |
| title | Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics |
| title_full | Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics |
| title_fullStr | Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics |
| title_full_unstemmed | Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics |
| title_short | Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics |
| title_sort | prospective study of pediatric patients presenting with idiopathic infantile nystagmus management and molecular diagnostics |
| topic | FRMD7 gene GPR143 gene nystagmus whole-genome sequencing albinism |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.977806/full |
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