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Branchiootorenal syndrome 1(BOR1)

MedGen UID:
1632634
Concept ID:
C4551702
Disease or Syndrome
Synonym: EYA1-Related Branchiootorenal Spectrum Disorders
 
Genes (locations): EYA1 (8q13.3); SIX1 (14q23.1)
 
Monarch Initiative: MONDO:0007236
OMIM®: 113650

Disease characteristics

Excerpted from the GeneReview: Branchiootorenal Spectrum Disorder
Branchiootorenal spectrum disorder (BORSD) is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial fistulae and cysts, and renal malformations ranging from mild renal hypoplasia to bilateral renal agenesis. Some individuals progress to end-stage renal disease (ESRD) later in life. Extreme variability can be observed in the presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality from right side to left side in an affected individual and also among individuals in the same family. [from GeneReviews]
Authors:
Richard JH Smith   view full author information

Additional descriptions

From OMIM
Branchiootorenal syndrome is an autosomal dominant disorder characterized by sensorineural, conductive, or mixed hearing loss, structural defects of the outer, middle, and inner ear, branchial fistulas or cysts, and renal abnormalities ranging from mild hypoplasia to complete absence. Reduced penetrance and variable expressivity has been observed (Fraser et al., 1978). Genetic Heterogeneity of Branchiootorenal Syndrome See also BOR2 (610896), caused by mutation in the SIX5 gene (600963) on chromosome 19q13. Sanchez-Valle et al. (2010) stated that approximately 40% of patients with BOR have mutations in the EYA1 gene and 5% have mutations in the SIX5 gene. See also branchiootic (BO) syndrome-1 (BOS1; 602588) and the otofaciocervical syndrome (OFC; 166780), allelic disorders showing overlapping phenotypes but without renal anomalies. See also 600257 for a discussion of the BOR-Duane-hydrocephalus contiguous gene syndrome as described by Vincent et al. (1994). Although Melnick et al. (1978) maintained that the BOR syndrome is distinct from the BO syndrome because in the latter condition renal anomaly is absent and deafness is not a constant feature, Cremers and Fikkers-van Noord (1980) concluded that the 2 syndromes are in fact a single entity.  http://www.omim.org/entry/113650
From MedlinePlus Genetics
"Renal" refers to the kidneys; BOR syndrome (but not BO syndrome) causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively.

"Oto-" and "-otic" refer to the ear; most people with BOR/BO syndrome have hearing loss and other ear abnormalities. The hearing loss can be sensorineural, meaning it is caused by abnormalities in the inner ear; conductive, meaning it results from changes in the small bones in the middle ear; or mixed, meaning it is caused by a combination of inner ear and middle ear abnormalities. Some affected people have tiny holes in the skin or extra bits of tissue just in front of the ear. These are called preauricular pits and preauricular tags, respectively.

Branchiootorenal (BOR) syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition vary widely, even among members of the same family. Branchiootic (BO) syndrome includes many of the same features as BOR syndrome, but affected individuals do not have kidney abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders).

"Branchio-" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with BOR/BO syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected people have abnormal holes or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause health problems if they become infected, so they are often removed surgically.  https://medlineplus.gov/genetics/condition/branchiootorenal-branchiootic-syndrome

Clinical features

From HPO
Polycystic kidney disease
MedGen UID:
9639
Concept ID:
C0022680
Disease or Syndrome
The presence of multiple cysts in both kidneys.
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Renal malrotation
MedGen UID:
68662
Concept ID:
C0238210
Congenital Abnormality
An abnormality of the normal developmental rotation of the kidney leading to an abnormal orientation of the kidney.
Unilateral renal agenesis
MedGen UID:
75607
Concept ID:
C0266294
Congenital Abnormality
A unilateral form of agenesis of the kidney.
Abnormal renal collecting system morphology
MedGen UID:
342720
Concept ID:
C1851303
Anatomical Abnormality
An abnormality of the renal collecting system.
Renal dysplasia
MedGen UID:
760690
Concept ID:
C3536714
Congenital Abnormality
The presence of developmental dysplasia of the kidney.
Renal steatosis
MedGen UID:
867423
Concept ID:
C4021796
Disease or Syndrome
Abnormal fat accumulation in the kidneys.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Cholesteatoma
MedGen UID:
3043
Concept ID:
C0008373
Disease or Syndrome
Cholesteatoma is a benign but potentially destructive growth consisting of keratinizing epithelium located in the middle ear and/or mastoid process. In cholesteatoma, a skin cyst grows into the middle ear and mastoid. The cyst is not cancerous but can erode tissue and cause destruction of the ear.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Mixed hearing impairment
MedGen UID:
102336
Concept ID:
C0155552
Disease or Syndrome
A type of hearing loss resulting from a combination of conductive hearing impairment and sensorineural hearing impairment.
Stenosis of the external auditory canal
MedGen UID:
140758
Concept ID:
C0395837
Finding
An abnormal narrowing of the external auditory canal.
Cupped ear
MedGen UID:
335186
Concept ID:
C1845447
Congenital Abnormality
Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).
Enlarged vestibular aqueduct syndrome
MedGen UID:
355050
Concept ID:
C1863752
Finding
Increased size of the vestibular aqueduct.
Dilatated internal auditory canal
MedGen UID:
382996
Concept ID:
C2676973
Finding
The presence of a dilated inner part of external acoustic meatus.
Hypoplasia of the cochlea
MedGen UID:
436824
Concept ID:
C2676974
Finding
Developmental hypoplasia of the cochlea.
Incomplete partition of the cochlea type II
MedGen UID:
892450
Concept ID:
C4025857
Finding
With incomplete partition II, the cochlea consists of 1.5 turns; the apical and middle cochlea turns are undifferentiated and form a cystic apex. The vestibule is normal while the vestibular aqueduct is always enlarged. Developmental arrest occurs at the seventh week of gestation.
Gustatory lacrimation
MedGen UID:
396279
Concept ID:
C1862052
Finding
Gustatory lacrimation results from an aberrant innervation of fibers from the seventh cranial nerve to the pterygopalatine ganglion which are destined originally for the submandibular ganglion. This aberrant innervation leads to uncontrollable tearing while eating or in anticipation of a meal.
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
Abnormal cerebral morphology
MedGen UID:
867394
Concept ID:
C4021762
Anatomical Abnormality
Any structural abnormality of the telencephalon, which is also known as the cerebrum.
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Branchial cyst
MedGen UID:
2342
Concept ID:
C0006131
Congenital Abnormality
A branchial cyst is a remnant of embryonic development resulting from a failure of obliteration of a branchial cleft and consists of a subcutaneous cystic mass. Cysts are located anterior or posterior to the ear or in the submandibular region.
Lacrimal duct stenosis
MedGen UID:
116054
Concept ID:
C0238300
Finding
Narrowing of a tear duct (lacrimal duct).
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Increased overbite
MedGen UID:
539656
Concept ID:
C0266063
Disease or Syndrome
Maxillary teeth cover the mandibular teeth when biting to an increased degree. The feature is defined as a vertical overlap of the maxillary incisors over the mandibular incisors that exceeds 2 mm.
Branchial fistula
MedGen UID:
107802
Concept ID:
C0546968
Congenital Abnormality
A congenital fistula in the neck resulting from incomplete closure of a branchial cleft.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Lacrimal duct aplasia
MedGen UID:
870330
Concept ID:
C4024773
Congenital Abnormality
A congenital defect resulting in absence of the lacrimal duct.
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Preauricular pit
MedGen UID:
120587
Concept ID:
C0266610
Congenital Abnormality
Small indentation anterior to the insertion of the ear.
Preauricular skin tag
MedGen UID:
395989
Concept ID:
C1860816
Finding
A rudimentary tag of skin often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear).
Euthyroid goiter
MedGen UID:
86230
Concept ID:
C0302859
Disease or Syndrome
DICER1 tumor predisposition (DICER1) is characterized by an increased risk for pleuropulmonary blastoma (PPB), pulmonary cysts, thyroid gland neoplasia (multinodular goiter, adenomas, and/or thyroid cancer), ovarian tumors (Sertoli-Leydig cell tumor, gynandroblastoma, and sarcoma), and cystic nephroma. Less commonly observed tumors include ciliary body medulloepithelioma, nasal chondromesenchymal hamartoma, embryonal rhabdomyosarcoma, pituitary blastoma, pineoblastoma, central nervous system (CNS) sarcoma, other CNS tumors, and presacral malignant teratoid tumor. The majority of tumors occur in individuals younger than age 40 years. PPB typically presents in infants and children younger than age six years. Ovarian sex cord-stromal tumors are most often diagnosed before age 40 years. Cystic nephroma generally presents in young children but has also been reported in adolescents. Additional clinical features that may be seen include macrocephaly, ocular abnormalities, structural anomalies of the kidney and collecting system, and dental anomalies (bulbous crowns).
Lacrimation abnormality
MedGen UID:
867427
Concept ID:
C4021801
Anatomical Abnormality
Abnormality of tear production.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

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