New Insights into Kleefstra Syndrome: Report of Two Novel Cases with Previously Unreported Features and Literature Review

Ciaccio, Claudia; Scuvera, Giulietta; Tucci, Arianna; Gentilin, Barbara; Baccarin, Marco; Marchisio, Paola; Avignone, Sabrina; Milani, Donatella

doi:10.1159/000494532

Cited by 27 publications

(28 citation statements)

References 20 publications

(58 reference statements)

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“…Kleefstra syndrome is caused by the either a deletion or a mutation of the EHMT1 gene. Approximately 20% to 30% of patients have hearing loss . Ayyash et al and Tug et al reported Kleefstra syndrome in patients aged 5 and 12 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Kleefstra syndrome is caused by a subtelomeric chromosomal abnormality resulting in either a heterozygous microdeletion in chromosomal region 9q34.3 or by a mutation in the euchromatin histone methyltransferase1 ( EHMT1 ) gene . It is inherited in an autosomal‐dominant manner, but almost all reported cases have occurred de novo.…”

Section: Introductionmentioning

confidence: 99%

“…Additional clinical features include congenital heart anomalies, urogenital defects, epilepsy, sleep disturbance, behavioral and psychiatric disorders, and obesity. Hearing loss occurs in approximately 20% to 30% of affected patients . The audiometric findings in Kleefstra syndrome include sensorineuronal and conductive hearing losses .…”

Section: Introductionmentioning

confidence: 99%

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Otopathology in Kleefstra Syndrome: A Case Report

et al. 2019

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Kleefstra syndrome is a rare neurogenetic disorder caused by a subtelomeric 9q34.3 deletion or by an intragenic mutation of the euchromatin histone methyl transferase 1 gene (EHMT1). Approximately 20% to 30% of individuals have hearing loss. The left temporal bone of one subject with hearing loss was studied using light microscopy. There were several abnormalities including dysostosis of the stapes without fixation, enlarged vestibular aqueduct, anomalies of the organ of Corti in the basal turn, cyst formation in the stria vascularis, and dysmorphia of the cochlear modiolus and the vestibular labyrinth. This is the first published description of the otopathology in Kleefstra syndrome. Laryngoscope, 130:2028–2033, 2020

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Otopathology in Kleefstra Syndrome: A Case Report

et al. 2019

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“…As more and more studies on the neurological aspects of the MDEM emerge, reports on other brain malformations are revealed. Searching the literature for OB hypoplasia/aplasia in these conditions unveiled a large number of studies involving CHARGE syndrome (Lin et al, 1990;Harvey et al, 1991;Pinto et al, 2005), but only a couple of human reports on RSTS and KLFS (Ajmone et al, 2018;Ciaccio et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Olfactory Malformations in Mendelian Disorders of the Epigenetic Machinery

Aleo

Cinnante

Avignone

et al. 2020

Front. Cell Dev. Biol.

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Usually overlooked by physicians, olfactory abnormalities are not uncommon. Olfactory malformations have recently been reported in an emerging group of genetic disorders called Mendelian Disorders of the Epigenetic Machinery (MDEM). This study aims to determine the prevalence of olfactory malformations in a heterogeneous group of subjects with MDEM. We reviewed the clinical data of 35 patients, 20 females and 15 males, with a mean age of 9.52 years (SD 4.99). All patients had a MDEM and an already available high-resolution brain MRI scan. Two experienced neuroradiologists reviewed the MR images, noting abnormalities and classifying olfactory malformations. Main findings included Corpus Callosum, Cerebellar vermis, and olfactory defects. The latter were found in 11/35 cases (31.4%), of which 7/11 had Rubinstein-Taybi syndrome (RSTS), 2/11 had CHARGE syndrome, 1/11 had Kleefstra syndrome (KLFS), and 1/11 had Weaver syndrome (WVS). The irregularities mainly concerned the olfactory bulbs and were bilateral in 9/11 patients. With over 30% of our sample having an olfactory malformation, this study reveals a possible new diagnostic marker for MDEM and links the epigenetic machinery to the development of the olfactory bulbs.

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“…However, previously reported cases were associated with other structural chromosomal abnormalities in addition to the deletion [45][46][47] . The DNA analysis was considered depending on ultrasound assessment result in prenatal cases [45][46][47][48][49][50] or visible clinical characteristics in postnatal cases [51][52][53][54] .…”

Section: Congenital Heart Malformationsmentioning

confidence: 99%

MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV

Stefekova¹,

Capkova²,

Capkova³

et al. 2022

BIOMED PAP

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The aim of this retrospective study was to determine the detection rate of the pathogenic copy number variants (CNVs) in a cohort of 33 foetuses -32 with CHD (congenital heart defects) and 1 with kidney defect, after exclusion of common aneuploidies (trisomy 13, 18, 21, and monosomy X) by karyotyping, Multiplex ligation -dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA). We also assess the effectivity of MLPA as a method of the first tier for quick and inexpensive detection of mutations, causing congenital malformations in foetuses. Methods. MLPA with probe mixes P070, P036 -Telomere 3 and 5, P245 -microdeletions, P250 -DiGeorge syndrome, and P311 -CHD (Congenital heart defects) was performed in 33 samples of amniotic fluid and chorionic villi. CMA was performed in 10 relevant cases. Results. Pathogenic CNVs were found in 5 samples: microdeletions in region 22q11.2 (≈2 Mb) in two foetuses, one distal microdeletion of the 22q11.2 region containing genes LZTR1, CRKL, AIFM3 and SNAP29 (≈416 kb) in the foetus with bilateral renal agenesis, 8p23.1 (3.8 Mb) microdeletion syndrome and microdeletion in area 9q34.3 (1.7 Mb, Kleefstra syndrome). MLPA as an initial screening method revealed unambiguously pathogenic CNVs in 15.2 % of samples. Conclusion.Our study suggests that MLPA and CMA are a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease. Determination of the cause of the abnormality is crucial for genetic counselling and further management of the pregnancy.

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New Insights into Kleefstra Syndrome: Report of Two Novel Cases with Previously Unreported Features and Literature Review

Cited by 27 publications

References 20 publications

Otopathology in Kleefstra Syndrome: A Case Report

Otopathology in Kleefstra Syndrome: A Case Report

Olfactory Malformations in Mendelian Disorders of the Epigenetic Machinery

MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV

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