Melnick-Fraser Syndrome

At a glance

It is a rare genetic disorder characterized by distinctive malformations of the head and facial area, with skin lesions and abnormalities of the eyes. It is characterized by a triad of symptoms that includes: (1) brachial fistulae or cysts; (2) Ear malformations; and (3) Kidney malformations (hypoplasia or agenesis). The clinical diagnostic is confirmed by the presence of bilateral renal dysplasia, Mendini-type cochlear malformation (hypoplasia of cochlear apex on CT scan), bilateral prehelical pits, and bilateral branchial cleft fistulas.

Synonyms

Branchio-Oto-Renal (BOR) Syndrome; Heusinger’s Syndrome.

History

This medical condition was first described in 1864 by Heusinger who identified an association of branchial cleft fistulae, preauricular pits, and hearing impairment in children. Subsequently, in 1975, John C. Melnick and Frank C. Fraser (b. 1920), a Canadian geneticist, described the BOR Syndrome as a specific entity with an autosomal dominant inheritance pattern.

Incidence

It is a rare medical condition that affects 1:40,000 live births in the general population. It is reported that approximately 2% of the affected children are profoundly deaf.

Genetic inheritance

Autosomal dominant; gene located on 8q13.3.

Pathophysiology

Not clearly defined, probably caused in great part by mutation of human EYA1 gene homologue of the Drosophila “eyes absent” gene (EYA). This gene is expressed in all areas of the developing inner ear and in the metanephric cells of the developing kidney, early in fetal development.

Diagnosis

Clinically evocated by pits or ear tags in front of the outer ear, branchial fistulas, branchial cysts, hearing loss, and abnormal development of the kidneys (polycystic or dysplasia). Prenatal diagnosis is possible.

Clinical aspects

This bipolar disease involves head and neck with auricular pits (77%); deafness that is perceptive, conductive, or mixed (89%); narrow auditory canal; and branchial cleft or cysts (63%). Cleft palate or uvula, facial paresis, microphthalmia, and absent nasolacrimal duct can be observed. Occasional deep prognathism. Genitourinary tract is the second pole of the disease (66%), ranging from minor dysplasia (double ureters, hydronephrosis, polycystic kidneys, supernumerary, ectopic, or small kidneys) to bilateral renal agenesis.

Precautions before anesthesia

Evaluate deafness (clinical, auditory evoked potentials, ear, nose, throat investigations). Evaluate renal function (clinical; echography/CT scan; scintigraphy; laboratory blood and urinary investigations, including urea and electrolytes).

Anesthetic considerations

Comprehension and cooperation of the patient is not always evident in case of deafness. Prognathism may make direct laryngoscopy and tracheal intubation difficult. In a case report of two siblings affected with BOR Syndrome and undergoing anesthesia, significant bradycardia during the sevoflurane general anesthesia was observed. Bradycardia occurred spontaneously at induction, maintenance, and ...