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Table 2 Clinical features of KCDCOM-associated diseases

From: KMT2C/D COMPASS complex-associated diseases [KCDCOM-ADs]: an emerging class of congenital regulopathies

 

KABUKI syndrome [60, 61, 65]

RUBENSTEIN-TAYBI syndrome [66,67,68,69]

KLEEFSTRA syndrome [70,71,72]

Gene(s)

KMT2D (Type 1)

CBP (Type 1)

EHMT1 (Type 1*)

 

KDM6A (Type 2)

EP300 (Type 2)

KMT2C (Type 2)

Growth

Post-natal growth restriction

Post-natal growth delay with subsequent excessive weight gain during childhood

Markedly reduced linear growth and head circumference. Normal, reduced or increased weight.

Craniofacial features

Head size

Variable microcephaly

Microcephaly

Brachycephaly

Eyes

Long palpebral fissures with eversion of the lateral one-third of the lower eyelid

Down-slanting palpebral fissures, long eye lashes

Hypertelorism

Eyebrows

Arch eyebrows with notching/sparseness of the lateral portion

Highly arched eyebrows

Synophrys (long, single eye brow)

Nose

Short columella with depressed nasal tip

Broad nasal bridge, beaked nose and prominent nasal septum extending below nares

Anteverted nares, macroglossia

Mouth/Lips

Tented upper lip

Small opening of mouth

Tented cupid’s bow portion of upper lip

Palate/Jaw

High arched palate with variable cleft, tooth abnormalities

High-arched palate with micrognathia

Prognathism

Ears

Large prominent cupped ears

Low set auricles

Thick ear helices

Cognitive and behavioral features

Mild to moderate intellectual disability with relative strength in verbal comprehension and more pronounced deficiencies in perceptual and nonverbal skills. Language and speech defects with expressive (dysarthria and dyspraxia) and expressive deficits.

Typically, moderate intellectual disability, ranging from mild to profound with relative weakness in working memory. Behavior characterized by high sociability but with challenges in communication, impulsivity, distraction, anxiety, and obsessive-compulsive attributes. Patients may also have mood disorders, tics and autistic behavior (more frequently in patients with CBP mutation vs EP300 mutation).

Mild, moderate or severe intellectual disability, language and delays, autistic behaviors, disordered sleeping, aggressive/hyperactive behaviors and auto-mutilatory behaviors

Other features

Skeletal anomalies (brachymesophalangy, brachydactyly V, vertebral defects, 5th digit clinodactyly) and dermatoglyphic abnormalities (persistent fingertip pads), seizure disorders. Hypogammaglobulinemia, autoimmunity

Small opening of mouth

Skeletal features: kyphosis and scoliosis. Seizure disorders