Kleefstra Syndrome

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Disease Ontology 12 DOID:0060352 MeSH 44 C563043 NCIt 50 C129976

KEGG 37 H00907 SNOMED-CT via HPO 69 204878001 204888000 34911001 197811007 236423003 42399005 43064006 25273001 13649004 271611007 109504005 22810007 194021007 22006008 15253005 103276001 15188001 343087000 95828007 21186006 708670007 246799009 253207002 5639000 248004009 61372001 5507002 84328007 130968006 162294008 229721007 29164008 62415009 128613002 246545002 313307000 84757009 91175000 398151007 398152000 224958001 5102002 414915002 414916001 253549006 30288003 86299006 72352009 7305005 249808002 397932003 14760008 225595004 16331000 235595009 698065002 367403001 230145002 267036007 278849000 53888004 609225004 50956007 72042002 111266001 64217002 95434006 249310005 237836003 95441000 16000003 40700009 102594003 44808001 698247007 414403008 52515009 more UMLS 73 C0795833 C0795834

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 261494Disease definitionKleefstra syndrome (KS) is a genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay and a distinctive facial appearance with a spectrum of additional clinical features.EpidemiologyThe prevalence is unknown. To date, 114 cases have been described.Clinical descriptionPatients with KS have a distinctive facial appearance comprised of brachy-microcephaly, midface hypoplasia, unusual eyebrow shape, synophyrs, cupid bow upper lip, full everted lower lip, protruding tongue and prognathism. With age, facial features become coarser and dental anomalies, like retention of primary dentition, are seen. Birth weight is normal but half of children go on to suffer from obesity. Childhood hypotonia causes motor delay but most children walk independently by age 2 or 3. Most patients have moderate to severe intellectual disability with expressive speech delay and little speech development (nonverbal communication is possible). Additional features include congenital heart malformations (interauricular communication, ventricular septal defects, bicuspid aortic valve, pulmonary valve stenosis (see these terms)), genital defects in males (hypospadias, cryptorchidism, micropenis), renal defects (hydronephrosis, chronic renal insufficiency, renal cysts, vesico-ureteral reflux), epilepsy, recurrent infections, severe constipation and hearing problems. In adolescence/adulthood behavioral problems (aggressive/emotional outbursts, attention deficit problems, self-mutilation and severe sleep disturbances) can begin. Autistic-like behavior can be noted earlier in some children. Recurrent pulmonary infections, overweight and behavioral problems seem to be reported more often in those with KS due to a point mutation, whereas microcephaly, short stature, respiratory complications and tracheomalacia are more frequently seen in those with KS due to a 9q34 microdeletion.EtiologyKS is caused by either a point mutation in the euchromatic histone-lysine N-methyltransferase 1 (EHMT1) gene (rarely) or by a microdeletion in the chromosome region 9q34.3 (seen in >85% of cases), leading to the loss of the entire gene. This gene encodes an enzyme that modifies histone function and is essential for normal development. Larger deletions (>1mb) are associated with more severe symptoms.Diagnostic methodsDiagnosis of KS is determined by the presence of the characteristic clinical features and molecular genetic testing. A microarray detects any duplications/deletions. Fluorescent in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) can then be used to detect the specific 9q34.3 deletion seen in KS. Sequencing of the entire coding region of the EHMT1 gene can detect sequence variants.Differential diagnosisDifferential diagnoses include Down, Pitt-Hopkins, Smith-Magenis, Rett and 2q23.1 microdeletion syndromes (see these terms).Antenatal diagnosisAntenatal diagnosis is offered to unaffected parents of a child with KS as they have a higher risk of having another child with this disorder.Genetic counselingMost reported cases have been de novo but familial recurrence has been seen. KS has a theoretical autosomal dominant transmission, but the majority of patients do not reproduce.Management and treatmentTreatment requires a multidisciplinary team, specializing in patients with intellectual deficiencies. Special education and vocational training along with speech therapy, physical and occupational therapy and sensory integration therapy are recommended from an early age. Standard treatment is necessary for those with renal, cardiac and urologic issues and for hearing loss. Psychiatric care along with behavioral intervention therapy may be needed. Cardiac screening (for the presence of arrhythmias) as well as intestinal and renal/urologic monitoring is recommended. Medical follow-up is life-long.PrognosisThe prognosis of KS is variable but in most cases it is not a life-threatening disease.Visit the Orphanet disease page for more resources.

MalaCards based summary : Kleefstra Syndrome, also known as chromosome 9q deletion syndrome, is related to kleefstra syndrome due to a point mutation and hypoplastic left heart syndrome, and has symptoms including seizures An important gene associated with Kleefstra Syndrome is EHMT1 (Euchromatic Histone Lysine Methyltransferase 1), and among its related pathways/superpathways are Lysine degradation and PKMTs methylate histone lysines. Affiliated tissues include tongue, eye and heart, and related phenotypes are malar flattening and hypertelorism

Disease Ontology : ¹² A syndrome characterized by childhood hypotonia, a distinctive facial appearance, speech impediments and developmental disability, as well as epilepsy, congenital and urogenetic defects, microcephaly, corpulence, and psychiatric disorders. It is caused either by a microdeletion in the chromosome region 9q34.3 or by a point mutation in the EHMT1 gene located in that region.

Genetics Home Reference : ²⁵ Kleefstra syndrome is a disorder that involves many parts of the body. Characteristic features of Kleefstra syndrome include developmental delay and intellectual disability, severely limited or absent speech, and weak muscle tone (hypotonia). Affected individuals also have an unusually small head size (microcephaly) and a wide, short skull (brachycephaly). Distinctive facial features include eyebrows that grow together in the middle (synophrys), widely spaced eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), nostrils that open to the front rather than downward (anteverted nares), a protruding jaw (prognathism), rolled out (everted) lips, and a large tongue (macroglossia). Affected individuals may have a high birth weight and childhood obesity.

Wikipedia : ⁷⁶ 9q34 deletion syndrome, also known as Kleefstra syndrome, is a rare genetic disorder. Terminal deletions... more...

GeneReviews: NBK47079

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased shRNA abundance (Z-score < -2)	GR00366-A-10	9.23	KMT2C
2	Decreased shRNA abundance (Z-score < -2)	GR00366-A-139	9.23	NOTCH1
3	Decreased shRNA abundance (Z-score < -2)	GR00366-A-165	9.23	KMT2C
4	Decreased shRNA abundance (Z-score < -2)	GR00366-A-22	9.23	KMT2C
5	Decreased shRNA abundance (Z-score < -2)	GR00366-A-28	9.23	KMT2C NOTCH1
6	Decreased shRNA abundance (Z-score < -2)	GR00366-A-65	9.23	NOTCH1
7	Decreased shRNA abundance (Z-score < -2)	GR00366-A-75	9.23	NOTCH1

Search Clinical Trials , NIH Clinical Center for Kleefstra Syndrome

Search GEO for disease gene expression data for Kleefstra Syndrome.