Branchio-oto-renal syndrome (BOR) is an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

involving the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s, ears, and neck. It often has also been described as Melnick-Fraser syndrome.

Signs and symptoms

The signs and symptoms of branchio-oto-renal syndrome are consistent with underdeveloped (

hypoplastic Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.absent Absence may refer to: Employment * Leave of absence, a period of time away from a job * Absenteeism, the habitual pattern of absence from work or duty * Absence rate, the ratio of workers with absences to total employees Sciences and philosophy ...

kidneys with resultant chronic kidney disease or

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

. Ear anomalies include extra openings in front of the ears, extra pieces of skin in front of the ears (preauricular tags), or further malformation or absence of the outer ear ( pinna). Malformation or absence of the

middle ear The middle ear is the portion of the ear medial to the eardrum, and distal to the oval window of the cochlea (of the inner ear). The mammalian middle ear contains three ossicles, which transfer the vibrations of the eardrum into waves in the ...

is also possible, individuals can have mild to profound hearing loss. People with BOR may also have cysts or

fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...

e along the sides of their neck. In some individuals and families, renal features are completely absent. The disease may then be termed "branchio-oto syndrome" (BO syndrome)., updated, 2015,

Cause

The cause of branchio-oto-renal syndrome are mutations in genes, EYA1,

SIX1 Homeobox protein SIX1 (Sine oculis homeobox homolog 1) is a protein that in humans is encoded by the ''SIX1'' gene. Function The vertebrate SIX genes are homologs of the Drosophila 'sine oculis' (so) gene, which is expressed primarily in the ...

, and

SIX5 Homeobox protein SIX5 is a protein that in humans is encoded by the ''SIX5'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...

(approximately 40 percent of those born with this condition have a mutation in the EYA1 gene). Many different abnormalities in these genes have been identified.

Mechanism

The

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...

of branchio-oto-renal syndrome indicate it is inherited in an autosomal dominant manner with variable clinical manifestations affecting branchial, renal, and auditory development. The varying clinical expression of the disease between different families suggests that multiple loci may be involved. In 1992, using genetic linkage studies, the BOR gene is identified on chromosome 8, Subsequently, another locus on human chromosome 14 is identified, and several mutations are reported in genes EYA1, SIX1, and SIX5. Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an

autosome An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. This gene is involved in many facets of embryonic development and is important in the normal formation of many

organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...

and tissues, including the ears, and kidneys before birth.

Diagnosis

Diagnosis of BO syndrome or BOR syndrome is clinical, i.e. based on observing an appropriate combination of symptoms. Only about half of patients have a detectable genetic abnormality, mostly in the EYA1 gene, SIX1 gene or the SIX5 gene.

Treatment

The treatment of branchio-oto-renal syndrome is done per each affected area (or organ). For example, a person with hearing problems should have appropriate supports and prompt attention for any inflammation of the

ear An ear is the organ that enables hearing and, in mammals, body balance using the vestibular system. In mammals, the ear is usually described as having three parts—the outer ear, the middle ear and the inner ear. The outer ear consists of ...

. A specialist should observe any kidney problems. Surgical repair may be needed depending on the degree of a defect or problem, whether a transplant or dialysis is needed.

Epidemiology

The epidemiology of branchio-oto-renal syndrome has it with a prevalence of 1/40,000 in

Western countries The Western world, also known as the West, primarily refers to the various nations and states in the regions of Europe, North America, and Oceania.

. A 2014 review found 250 such cases in the country of Japan.

References

External links

{{Medicine Syndromes affecting hearing Autosomal dominant disorders Syndromes affecting the kidneys Rare syndromes