Clinical Guidance

No clear genotype-phenotype correlation exists. Significant inter- and intrafamilial variability have been observed with the same pathogenic variants . Missense, frameshift, and splicing variants along with more complex rearrangements throughout the gene result in similar phenotypes. The majority of individuals with a deletion involving TFAP2A appear to have an abnormally prominent philtrum that may be on the spectrum of microform cleft lip . described an infant and mother with a 593-kb deletion including TFAP2A and five additional genes. Neither is reported to have any type of cleft or abnormal philtrum. Otherwise, the marked inter- and intrafamilial variability appear similar to that observed with intragenic pathogenic variants.

Source: GeneReviews — "Branchiooculofacial Syndrome"

Penetrance

BOFS has shown almost complete penetrance. Careful examination of individuals identified in a family with BOFS with a TFAP2A pathogenic variant is necessary to reveal subtle findings including premature graying (individuals may have dyed their hair), faint hair on the neck, or heterochromia of the irides.

Source: GeneReviews — "Branchiooculofacial Syndrome"

Diagnostic Criteria

There are no formal diagnostic guidelines for branchiooculofacial syndrome (BOFS) developed by consensus panels, algorithms using a hierarchy of clinical findings, or evidence-based test standards. Diagnostic criteria have been proposed (see Table I in ).

Suggestive Findings

BOFS should be suspected in probands with findings in two or three of the following categories. Branchial (cutaneous) defects. Cervical or infra- or supra-auricular skin defects:

Source: GeneReviews — "Branchiooculofacial Syndrome"

Differential Diagnosis

The branchiooculofacial syndrome phenotype is distinctive and can typically be differentiated on a clinical basis from disorders with overlapping features . Table 2. Disorders of Interest in the Differential Diagnosis of Branchiooculofacial Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with branchiooculofacial syndrome (BOFS), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Branchiooculofacial Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "Branchiooculofacial 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 — "Branchiooculofacial Syndrome"

Surveillance Guidelines

To monitor existing manifestations and the individual's response to supportive care, the evaluations summarized in are recommended. Table 5. Branchiooculofacial Syndrome: Recommended Surveillance

Source: GeneReviews — "Branchiooculofacial Syndrome"