CNS malformations in Knobloch syndrome with splice mutation in <i>COL18A1</i> gene

Keren, Boris; Suzuki, Oscar; Gérard-Blanluet, Marion; Brémond‐Gignac, Dominique; Elmaleh, Monique; Titomanlio, Luigi; Delezoide, Anne‐Lise; Passos‐Bueno, Maria Rita; Verloes, Alain

doi:10.1002/ajmg.a.31784

Cited by 34 publications

(28 citation statements)

References 24 publications

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“…Of the 34 previously described mutation-positive non-Saudi cases,5–11 13 14 only four have published fundus images and these are limited 7 10 14 17. One is blurry 7.…”

Section: Discussionmentioning

confidence: 99%

The distinct ophthalmic phenotype of Knobloch syndrome in children

et al. 2012

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“…Of the 34 previously described mutation-positive non-Saudi cases,5–11 13 14 only four have published fundus images and these are limited 7 10 14 17. One is blurry 7.…”

Section: Discussionmentioning

confidence: 99%

The distinct ophthalmic phenotype of Knobloch syndrome in children

et al. 2012

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“…Knobloch syndrome is characterized by the occurrence of high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele, which is a neural tube closure defect (Passos-Bueno et al, 2006; Table 1). A few cases with defects in neuronal migration, seen as heterotopic nodules in the brain, have been reported (Kliemann et al, 2003;Keren et al, 2007). There is some evidence that Knobloch syndrome may predispose patients to epilepsy (Suzuki et al, 2002), and persistence of the fetal vasculature of the eye has been reported in one patient (Duh et al, 2004).…”

Section: Mutations In Collagen XVIII Lead To Knobloch Syndromementioning

confidence: 99%

The multiple functions of collagen XVIII in development and disease

2011

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“…Neuroradiologic imaging has revealed a variety of developmental brain anomalies including occipital skull defects with or without encephalocele, polymicrogyria, subependymal nodules, and cerebellar vermis atrophy. 5,[7][8][9][10] Additional systemic findings include epilepsy, developmental delay, and renal abnormalities.…”

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confidence: 99%

Molecular and Clinical Findings in Patients With Knobloch Syndrome

Hull

Arno

et al. 2016

JAMA Ophthalmol

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IMPORTANCE Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described.OBJECTIVE To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome. DESIGN, SETTING, AND PARTICIPANTSTwelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015. MAIN OUTCOMES AND MEASURESResults of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1. RESULTSOf the 12 patients (6 males; mean age at last review, 16 years [range, 2-38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children. CONCLUSIONS AND RELEVANCEThis report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications.

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CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene

Cited by 34 publications

References 24 publications

The distinct ophthalmic phenotype of Knobloch syndrome in children

The distinct ophthalmic phenotype of Knobloch syndrome in children

The multiple functions of collagen XVIII in development and disease

Molecular and Clinical Findings in Patients With Knobloch Syndrome

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