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Kleefstra syndrome 2(KLEFS2)

MedGen UID:
1623903
Concept ID:
C4540395
Disease or Syndrome
Synonym: KLEFS2
 
Gene (location): KMT2C (7q36.1)
 
Monarch Initiative: MONDO:0054701
OMIM®: 617768

Definition

Kleefstra syndrome-2 (KLEFS2) is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features (summary by Koemans et al., 2017). For a discussion of genetic heterogeneity of Kleefstra syndrome, see KLEFS1 (610253). [from OMIM]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Plagiocephaly
MedGen UID:
1825944
Concept ID:
C2081594
Finding
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Abnormal facial shape
MedGen UID:
98409
Concept ID:
C0424503
Finding
An abnormal morphology (form) of the face or its components.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.

Professional guidelines

PubMed

Barili V, Ambrosini E, Uliana V, Bellini M, Vitetta G, Martorana D, Cannizzaro IR, Taiani A, De Sensi E, Caggiati P, Hilton S, Banka S, Percesepe A
Genes (Basel) 2023 Jun 10;14(6) doi: 10.3390/genes14061241. PMID: 37372421Free PMC Article

Recent clinical studies

Diagnosis

Yamada M, Suzuki H, Miya F, Kosugiyama K, Ujiie T, Tonoki H, Kosaki K
Congenit Anom (Kyoto) 2023 Jul;63(4):121-124. Epub 2023 Mar 28 doi: 10.1111/cga.12514. PMID: 36946065

Prognosis

Whitford W, Taylor J, Hayes I, Smith W, Snell RG, Lehnert K, Jacobsen JC
Mol Genet Genomic Med 2024 Jan;12(1):e2350. Epub 2023 Dec 26 doi: 10.1002/mgg3.2350. PMID: 38146907Free PMC Article

Clinical prediction guides

Whitford W, Taylor J, Hayes I, Smith W, Snell RG, Lehnert K, Jacobsen JC
Mol Genet Genomic Med 2024 Jan;12(1):e2350. Epub 2023 Dec 26 doi: 10.1002/mgg3.2350. PMID: 38146907Free PMC Article

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