Clinical Guidance

This section summarizes findings in more than 400 individuals with a molecularly confirmed diagnosis of Kabuki syndrome (KS).

Growth

Individuals with KS typically exhibit normal growth parameters at birth.

Source: GeneReviews — "Kabuki Syndrome"

Penetrance

Penetrance for pathogenic variants in KMT2D appears to be complete; not enough information is available to make any conclusions regarding penetrance for those with pathogenic variants in KDM6A. Variable expressivity may lead to underascertainment of mildly affected individuals.

Source: GeneReviews — "Kabuki Syndrome"

Differential Diagnosis

Table 2.

Disorders to Consider in the Differential Diagnosis of Kabuki Syndrome (KS)

Disorder | Gene(s) | MOI | Clinical Features

Overlapping w/KS | Distinguishing from KS

CHARGE syndrome

| CHD7 | AD | • Cleft palate

• Congenital heart defects

• Ocular coloboma

• Growth restriction

| In CHARGE syndrome:

• Square face

• Short, wide ear w/little or no earlobe

• Prominent columella

• Broad nasal root

In KS: fingertip pads

22q11.2 deletion syndrome | See footnote 1. | AD | • Cleft palate

• Congenital heart defects

• Urinary tract anomalies

| In 22q11 deletion syndrome:

• Short narrow palpebral fissures w/hooded eyelids

• Bulbous nasal tip

• Small, C-shaped ears w/overfolded superior /or lateral helices

IRF6-related disorders2 | IRF6 | AD | • Cleft lip palate

• Lip pits

Source: GeneReviews — "Kabuki Syndrome"

Clinical Guidance

In those with joint laxity, activities that increase the risk of joint damage (e.g., bouncing on a trampoline) should be avoided.

Source: GeneReviews — "Kabuki Syndrome"

Therapies Under Investigation

Based on the function of KMT2D and KDM6A as regulators of chromatin expression , it has been hypothesized that histone deacetylase inhibitors (HDACi) could have a beneficial effect on individuals with Kabuki syndrome. created a mouse model of KS and found that treatment with HDACi normalized the structural and functional differences seen in certain brain areas in these affected mice, leading to improved neurogenesis and memory. This has yet to be tested in humans with KS, but clinical trials based on these mouse studies are in the planning phase. Since ketosis acts as an endogenous HDACi, others have hypothesized that placing individuals with KS on a ketogenic diet could improve their cognitive issues .

Source: GeneReviews — "Kabuki Syndrome"