Kleefstra Syndrome

Submicroscopic and subtelomeric deletions of the q region of chromosome 9 that result in severe intellectual disability, epilepsy, heart defects, BRACHYCEPHALY or MICROCEPHALY; MACROGLOSSIA and other craniofacial abnormalities. The symptoms are caused by deletion or mutation of the EHMT1 gene. OMIM: 610253

Also Known As:

Networked: 40 relevant articles (0 outcomes, 3 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Autism Spectrum Disorder
2.	Coffin-Siris syndrome
3.	Intellectual Disability (Idiocy)
4.	Neurodevelopmental Disorders
5.	Inborn Genetic Diseases (Disease, Hereditary)

Experts

1.	van Bokhoven, Hans: 10 articles (10/2019 - 07/2012)
2.	Kleefstra, Tjitske: 9 articles (10/2019 - 07/2012)
3.	Zhou, Huiqing: 6 articles (10/2019 - 07/2012)
4.	Benevento, Marco: 6 articles (01/2018 - 03/2013)
5.	Nadif Kasri, Nael: 5 articles (12/2020 - 02/2014)
6.	Frega, Monica: 4 articles (10/2019 - 01/2016)
7.	Kasri, Nael Nadif: 4 articles (01/2018 - 07/2012)
8.	Schubert, Dirk: 3 articles (12/2020 - 10/2016)
9.	Van der Zee, Catharina E E M: 3 articles (10/2017 - 03/2013)
10.	Shinkai, Yoichi: 2 articles (07/2021 - 03/2013)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Kleefstra Syndrome:

1.	Histones (Histone)IBA 03/01/2017 - "Kleefstra Syndrome (KS) (MIM# 610253) is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 (EHMT1, GLP). " 01/01/2017 - "Kleefstra syndrome (KS) (Mendelian Inheritance in Man (MIM) no. 610253), also known as 9q34 deletion syndrome, is an autosomal dominant disorder caused by haploinsufficiency of euchromatic histone methyltransferase-1 (EHMT1). " 10/01/2023 - "Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. " 01/01/2016 - "Histone Methylation by the Kleefstra Syndrome Protein EHMT1 Mediates Homeostatic Synaptic Scaling." 01/01/2020 - "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). "
2.	MethyltransferasesIBA 02/01/2022 - "We report an eight-month baby boy with Kleefstra syndrome type 2 due to a novel de novo pathogenic mutation in the KMT2C (Lysine methyltransferase 2C) gene. " 03/03/2019 - "From large-scale human DNA sequencing studies, we further propose that the lysine methyltransferase gene, KMT5B (OMIM: 610881), may fit into a category of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900), respectively. " 07/23/2021 - "Haploinsufficiency of EHMT1, which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. "
3.	Lysine (L-Lysine)FDA Link 02/01/2022 - "We report an eight-month baby boy with Kleefstra syndrome type 2 due to a novel de novo pathogenic mutation in the KMT2C (Lysine methyltransferase 2C) gene. " 03/03/2019 - "From large-scale human DNA sequencing studies, we further propose that the lysine methyltransferase gene, KMT5B (OMIM: 610881), may fit into a category of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900), respectively. " 07/23/2021 - "Haploinsufficiency of EHMT1, which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. "
4.	EnzymesIBA 05/01/2020 - "Kleefstra syndrome (KS) is an autosomal dominant disorder caused by a chromosomal deletion at 9q34.3 resulting in pathogenic variants of the gene that codes for the enzyme, euchromatin histone methyltransferase 1 (EHMT1). " 01/01/2023 - "Recent studies in humans have identified mutations in KMT2C, an enzyme responsible for modifying histone tails and depositing H3K4me1 and H3K4me3, as being associated with Kleefstra syndrome 2 and autism spectrum disorder (ASD). " 02/15/2014 - "Haploinsufficiency of Euchromatin histone methyltransferase 1 (EHMT1), a chromatin modifying enzyme, is the cause of Kleefstra syndrome (KS). "
5.	DNA (Deoxyribonucleic Acid)IBA 01/01/2022 - "We detected low-level mosaicism in sperm-derived DNA but not in blood in the father of a child with Kleefstra syndrome caused by an EHMT1 variant. " 03/03/2019 - "From large-scale human DNA sequencing studies, we further propose that the lysine methyltransferase gene, KMT5B (OMIM: 610881), may fit into a category of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900), respectively. "
6.	Biomarkers (Surrogate Marker)IBA 11/01/2016 - "Our model might offer a good platform to study the pathomechanism of Kleefstra syndrome, also for drug testing, early biomarker discovery and gene therapy studies."
7.	histone H3 trimethyl Lys4IBA 01/01/2023 - "Recent studies in humans have identified mutations in KMT2C, an enzyme responsible for modifying histone tails and depositing H3K4me1 and H3K4me3, as being associated with Kleefstra syndrome 2 and autism spectrum disorder (ASD). "
8.	Histone MethyltransferasesIBA 01/01/2018 - "Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransferases responsible for deposition of the di-methylated H3K9 (H3K9me2), the exact nature of epigenetic dysfunctions in Kleefstra syndrome remains unknown. " 12/01/2021 - "Kleefstra syndrome (KS) is a rare autosomic dominant genetic disorder caused by euchromatic histone methyltransferase 1 (EHMT1) alterations. " 12/01/2020 - "Mutations in the Euchromatic Histone Methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a rare form of intellectual disability (ID) with strong autistic traits and sensory processing deficits. " 10/30/2019 - "Kleefstra syndrome (KS) is a neurodevelopmental disorder caused by mutations in the histone methyltransferase EHMT1. " 01/01/2023 - "EHMT1 is an epigenetic factor with histone methyltransferase activity that appears mutated in Kleefstra syndrome, a neurodevelopmental genetic disorder characterized by developmental delay, intellectual disability, and autistic-like features. "
9.	EuchromatinIBA 01/01/2023 - "Multiple Mongolian spots in an individual with Kleefstra syndrome caused by a novel nonsense euchromatin histone methyltransferase 1 variant." 01/01/2022 - "As proof-of-principle, we investigated an EHMT1 (Euchromatin histone methyltransferase 1; EHMT1 c.3430C > T; p.Gln1144*) genetic variant pathogenic for Kleefstra syndrome and determined changes in gene expression during neuronal progenitor cell differentiation. " 03/01/2013 - "Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome." 02/15/2014 - "Reduced Euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice." 01/01/2018 - "A germline genetic defect affecting the euchromatin histone methyltransferase 1 (EHMT1) gene causes Kleefstra syndrome, which is associated with the typical triad of distinct facial appearance, (childhood) hypotonia, and intellectual disability. "
10.	TransferasesIBA 10/01/2023 - "Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. " 01/01/2020 - "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). " 01/01/2016 - "The underlying cause of the syndrome is a submicroscopic deletion in the chromosomal region 9q34.3 or disruption of the euchromatin histone methyl transferase 1. We describe two Hungarian Kleefstra syndrome patients, one with the classic phenotype of the syndrome, the diagnosis was confirmed by subtelomeric FISH. " 07/01/2011 - "The Kleefstra syndrome (Online Mendelian Inheritance in Man 607001) is caused by a submicroscopic 9q34.3 deletion or by intragenic euchromatin histone methyl transferase 1 (EHMT1) mutations. " 01/01/2018 - "Kleefstra Syndrome is a rare genetic disorder caused by mutations in EHMT1, Euchromatin Histone Methyl Transferase 1, or deletions encompassing EHMT1 on 9q34.3. Congenital heart defects are among the major findings in patients with 9q34.3 microdeletion/Kleefstra Syndrome along with recognizable facial appearance, developmental delay/intellectual disability including severely delayed or absent speech, hypotonia, seizures, behavioral and sleep abnormalities. "

Therapies and Procedures

1.	Deep Brain Stimulation 06/01/2015 - "Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome."
2.	Therapeutics 01/01/2023 - "This is the first report of psychotic symptoms fully remitting in response to zuclopenthixol therapy in an individual with Kleefstra syndrome. "
3.	Spinal Fusion (Spondylosyndesis) 09/01/2020 - "There is a paucity of literature describing posterior spinal fusion in the Kleefstra syndrome patient. "