Intragenic<i>KANSL1</i>mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype–phenotype correlations in a large cohort of patients

Zollino, Marcella; Marangi, Giuseppe; Ponzi, Emanuela; Orteschi, Daniela; Ricciardi, Stefania; Lattante, Serena; Murdolo, Marina; Battaglia, Domenica; Contaldo, Ilaria; Mercuri, Eugenio; Stefanini, Maria Cristina; Caumes, Roseline; Edery, Patrick; Rossi, Massimiliano; Piccione, Maria; Corsello, Giovanni; Monica, Matteo Della; Scarano, Francesca; Priolo, Manuela; Gentile, Mattia; Zampino, Giuseppe; Vijzelaar, Raymon; Abdul‐Rahman, Omar; Rauch, Anita; Oneda, Beatrice; Deardorff, Matthew A.; Saitta, Sulagna C.; Falk, Marni J.; Dubbs, Holly; Zackai, Elaine H.

doi:10.1136/jmedgenet-2015-103184

Cited by 46 publications

(55 citation statements)

References 15 publications

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“…Additional features include overly social and friendly behaviour, epilepsy, congenital heart defects, urogenital malformations, musculoskeletal anomalies and ectodermal anomalies. Zollino et al reported a deletion patient (patient 28) with hypoplastic ocular globe, unilateral ONH, strabismus, hearing impairment and craniosynostosis 65. Koolen et al reported another deletion patient (case 32) with ONH, hypermetropia, strabismus, esotropia and corpus callosum abnormality 66.…”

Section: Introductionmentioning

confidence: 99%

Genetic causes of optic nerve hypoplasia

Yin

Lewis

2017

J Med Genet

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Optic nerve hypoplasia (ONH) is the most common congenital optic nerve anomaly and a leading cause of blindness in the USA. Although most cases of ONH occur as isolated cases within their respective families, the advancement in molecular diagnostic technology has made us realise that a substantial fraction of cases has identifiable genetic causes, typically de novo mutations. An increasing number of genes has been reported, mutations of which can cause ONH. Many of the genes involved serve as transcription factors, participating in an intricate multistep process critical to eye development and neurogenesis in the neural retina. This review will discuss the respective genes and mutations, human phenotypes, and animal models that have been created to gain a deeper understanding of the disorders. The identification of the underlying gene and mutation provides an important step in diagnosis, medical care and counselling for the affected individuals and their families. We envision that future research will lead to further disease gene identification, but will also teach us about gene-gene and gene-environment interactions relevant to optic nerve development. How much of the functional impairment of the various forms of ONH is a reflection of altered morphogenesis versus neuronal homeostasis will determine the prospect of therapeutic intervention, with the ultimate goal of improving the quality of life of the individuals affected with ONH.

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Section: Introductionmentioning

confidence: 99%

Genetic causes of optic nerve hypoplasia

Yin

Lewis

2017

J Med Genet

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confidence: 99%

“…Phenotyping studies have noted that roughly half of individuals with KdVS have seizures during their lifetime; however, the epileptology remains poorly understood. Although both focal and generalized seizures have been reported, the epilepsy phenotypic spectrum has not been defined . A typical neuroradiologic pattern has not been described, although structural brain abnormalities are reported in approximately half, including corpus callosum dysgenesis, enlarged lateral ventricles, abnormal hippocampal shape, Chiari I malformation, and subependymal heterotopia .…”

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confidence: 99%

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

et al. 2017

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The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features. Multifocal epileptiform discharges are the typical EEG pattern. Structural brain abnormalities may be universal, including signs of abnormal neuroblast migration and abnormal axonal guidance. Epilepsy surgery should be undertaken with care given the widespread neuroanatomic abnormalities; however, tumors are a rare, yet important, occurrence.

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“…In particular, 7 adult patients (aged >18 years, range 20-50 years) are included in the series reported by Koolen et al [2016] and 2 young adults (23-and 31-years-old) are described in the cohort reported by Zollino et al [2015]. Clinical and molecular data of these patients are summarized in table 1 .…”

Section: Discussionmentioning

confidence: 99%

“…Most of the patients (58-73%) show joint hypermobility (JHM) during childhood, sometimes leading to hip dislocations (congenital or acquired) or positional deformities of the feet [Tan et al, 2009, Koolen et al, 2016. Additional features may include short stature according to genetic target, hearing loss (conductive, sensorineural or mixed, 26%), ectodermal abnormalities, hypermetropia, and other ocular defects [Zollino et al, 2015, Koolen et al, 2016]. …”

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confidence: 99%

Koolen-de Vries Syndrome: Clinical Report of an Adult and Literature Review

Ciaccio

Dordoni

Ritelli

et al. 2016

Cytogenet Genome Res

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Koolen-de Vries syndrome (KdS) is a rare genetic condition characterized by typical facial dysmorphisms, cardiac and renal defects, skeletal anomalies, developmental delay, and intellectual disability of variable level. It is caused by a 440-680-kb deletion in the 17q21.31 region, encompassing CRHR1, MAPT, IMP5, STH, and KANSL1, or by an intragenic KANSL1 mutation. The majority of the patients reported are pediatric or young adults, and long-term studies able to define the prognosis of the disease are lacking. Here, we report a patient in the fourth decade misdiagnosed in the past as classical Ehlers-Danlos syndrome for the presence of generalized joint hypermobility, who carried a 546-kb deletion in 17q21.31, and compare his phenotype with those of the few KdS adults (aged >18 years) described so far. We observed a favorable prognosis of epilepsy and cardiovascular signs and reduction of joint hypermobility with age, thus providing insight into the natural history of the disorder.

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IntragenicKANSL1mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype–phenotype correlations in a large cohort of patients

Cited by 46 publications

References 15 publications

Genetic causes of optic nerve hypoplasia

Genetic causes of optic nerve hypoplasia

The epileptology of Koolen‐de Vries syndrome: Electro‐clinico‐radiologic findings in 31 patients

Koolen-de Vries Syndrome: Clinical Report of an Adult and Literature Review

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