Clinical Guidance

The vast majority of pathogenic variants are loss-of-function variants. No specific genotype/phenotype correlations have been reported, with the exception of those who have a larger 16q24.3 deletion. 16q24.3 deletions. Individuals with a 16q24.3 deletion have the findings of KBG syndrome listed previously in addition to intellectual disability and autism spectrum disorder (although the increased frequency of autism spectrum diagnoses in this cohort may be a result of ascertainment bias) [, , , ].

Source: GeneReviews — "KBG Syndrome"

Diagnostic Criteria

While no consensus clinical diagnostic criteria for KBG syndrome have been published, several authors have suggested diagnostic criteria .

Suggestive Findings

KBG syndrome should be suspected in a proband with developmental delay/ cognitive impairment or significant behavioral issues who has [, , , ]:

• At least two of the findings highlighted by an asterisk (*); OR

• One finding highlighted by an asterisk and at least two additional findings.

Craniofacial features

• *Macrodontia (mesiodistal width of permanent central incisors ≥10 mm in males, ≥9.7 mm in females) , especially of the upper central incisors

• *Characteristic facial appearance (See .)

• Conductive hearing loss and/or chronic/recurrent otitis media

• Palatal abnormalities

• Hair anomalies (e.g., low hairline, coarse hair)

Skeletal features

Source: GeneReviews — "KBG Syndrome"

Differential Diagnosis

Table 2.

Disorders to Consider in the Differential Diagnosis of KBG Syndrome

DiffDx Disorder | Gene(s) | MOI | Clinical Features of Disorder

Overlapping w/KBG syndrome | Distinguishing from KBG syndrome

Cornelia de Lange syndrome

| NIPBL

SMC1A

HDAC8

SMC3

RAD21

| ADXL | • Facial features

• DD

• Growth restriction

• Hearing loss

• Cryptorchidism

| Typically:

• Head circumference small

• ID more severe

Silver-Russell syndrome

| See footnote 1. | See footnote 1. | • Facial features

• DD

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with KBG syndrome, the evaluations summarized (if they have not already been completed) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis of KBG Syndrome

Source: GeneReviews — "KBG Syndrome"

Clinical Guidance

Because of the risk of hearing loss, ototoxic drugs should be avoided.

Source: GeneReviews — "KBG Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "KBG Syndrome"

Surveillance Guidelines

Routine monitoring for the following should be considered:

• Hearing, to assess for hearing loss

• Vision, if ophthalmologic issues are present

• Growth and pubertal status, to assess for short stature, growth velocity, and advanced or premature puberty

• Regular developmental assessments to evaluate cognition and learning

Source: GeneReviews — "KBG Syndrome"