Prospective study of pediatric patients presenting with idiopathic infantile nystagmus—Management and molecular diagnostics

Abstract

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.

Managing the apparently blind child presenting in the first year of life: A review

“…97 Idiopathic infantile nystagmus (IIN) is frequently associated with FRMD7 mutations although there is significant genetic heterogeneity with more than 100 genes reported to be associated. 98,99 Oculocutaneous albinism frequently associated with nystagmus is associated with mutations in TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3) and SLC45A2 (OCA4), whilst ocular albinism is associated with the X-linked gene OA. [98][99][100][101][102][103] PAX6 is another gene associated with multiple phenotypes, including aniridia, anterior segment dysgenesis, optic nerve hypoplasia, and microphthalmia, in addition to isolated foveal hypoplasia and nystagmus.…”

“…98,99 Oculocutaneous albinism frequently associated with nystagmus is associated with mutations in TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3) and SLC45A2 (OCA4), whilst ocular albinism is associated with the X-linked gene OA. [98][99][100][101][102][103] PAX6 is another gene associated with multiple phenotypes, including aniridia, anterior segment dysgenesis, optic nerve hypoplasia, and microphthalmia, in addition to isolated foveal hypoplasia and nystagmus. 98,100,104 The aniridia phenotype has a high mutation detection rate for PAX6 of approximately 80%-90%.…”

“…Idiopathic infantile nystagmus (IIN) is frequently associated with FRMD7 mutations although there is significant genetic heterogeneity with more than 100 genes reported to be associated 98,99 . Oculocutaneous albinism frequently associated with nystagmus is associated with mutations in TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3) and SLC45A2 (OCA4), whilst ocular albinism is associated with the X‐linked gene OA 98‐103 …”

Nistagmo no vestibular e intrusiones sacádicas no nistágmicas

“…Tiene una prevalencia de 1/1500 niños, dos veces más frecuente en varones. Supone un 8 % de todos los nistagmos [1,10].…”

Visual Function and Neuropsychological Profiling of Idiopathic Infantile Nystagmus

“…Its aetiology is not completely known yet, though there is a relative consensus on its genetic origin. Both sporadic and inherited (autosomal dominant, recessive, X-linked) forms have been reported, with FRMD7, GPR143 and CASK considered causative genes [ 10 , 11 ]. Nevertheless, the underlying pathogenic mechanisms have not been clarified yet.…”