© The authors, 2019

Observation

A 19-week-old child presented with two small bilateral labial commissural pits as her primary complaint was evaluated by a multidisciplinary team consisting of pediatric, oral, dermatology consultants (Fig. 1). The lesions were more pronounced on the left side. No seromucous flow was noted around these pits. No other lesions of the same type were found in the rest of the body. The rest of the clinical examination revealed a prominent notch in the lower part of the aural helix bilaterally (Fig. 2), with a clinical anomaly, which predominately affected the right ear. The patient's maternal uncle and half-brother had a similar unilateral lesion of the right antihelix. A renal malformation was also present in a maternal uncle and in a great maternal aunt.

The child was in good general condition and had a satisfactory height-weight development.

The overall clinical picture of the child and the presence of familial abnormalities led to the suspicion of branchio-oto–renal syndrome (BOR), and a renal ultrasound was performed. A megalo-pelvis (pyelic hypotonia) was observed, with the renal pelvis measuring 3.9 mm in the anteroposterior dimension.

Fig. 1 Bilateral commissural pits without flows.

Fig. 2 Ear anomaly with marked notch on the antihelix.

Discussion

BOR syndrome is an autosomal dominant disorder most often caused by an EYA1 mutation. It is a rare disease with an incidence of 1 case in every 40,000 in Western countries [1]. EYA1 is the gene most frequently implicated in BOR syndrome. It is located on the long arm of chromosome 8 [2] and encodes for a transcriptional regulator named Ey. Point mutations and deletions, in particular, have been identified in this gene in approximately 40% of affected patients. The first case was reported by Melnick in the late 1970s [1]. In vivo studies have reported renal abnormalities and hearing disorders, similar to that observed in the human phenotype, in mice with heterozygous and homozygous EYA1 mutations [3]. SIX1 and SIX5 mutations can also cause BOR syndrome [1].

BOR syndrome is clinically diagnosed on the basis of numerous clinical criteria, which are subclassified into major and minor [4].

In the absence of a family history, either three major criteria alone or two major criteria combined with two minor criteria must be present for a clinical diagnosis. However, with a positive family history, only one major criterion is sufficient for a diagnosis.

The major criteria are as follows:

• a second branchial arch anomaly (lateral cervical swelling outside the sternocleidomastoid muscle, fistula at the anterior border of the sternocleidomastoid muscle);

• deafness;

• preauricular pits;

• auricular malformations;

• and renal abnormalities.

The minor criteria are as follows:

• abnormalities of the external auditory canal;

• middle ear abnormalities;

• inner ear abnormalities;

• preauricular tags (skin nodule);

• facial asymmetry;

• palatal abnormalities.

A complementary genomic molecular analysis can be performed to look for EYA1, SIX5, or SIX1 mutations.

The present case presented with three major criteria: labial commisural pits, auricular malformation, and renal abnormality, allowing for confirmation of BOR syndrome. The existence of familial renal and auricular abnormalities supported the diagnosis.

Differential diagnoses are branchio-oculo–facial syndrome and Goldenhar syndrome [5].

The management of this pathology is multidisciplinary. The anomalies of the second branchial arch are treated by antibiotic therapy in case of superinfections. Surgery can also be used to treat recurrent infectious episodes.

Urgent management of hearing disorder would help to avoid any problems with language learning in affected children. Treatment may be in the form of tympanoplasty or cochlear implant placement.

In addition, regular renal monitoring in warranted, and surgery may be required for treating obstructive pathologies. Renal hypoplasia and dysplasia may cause renal failure, requiring dialysis or kidney transplantation.

Conflict of interests

The authors declares that they have no conflicts of interest in relation to this article

References

All Figures

	Fig. 1 Bilateral commissural pits without flows.
In the text

	Fig. 2 Ear anomaly with marked notch on the antihelix.
In the text