Alport Syndrome
Alport syndrome is characterized by renal, cochlear, and ocular involvement. The
main manifestation is glomerular nephropathy with hematuria, progressing to endstage renal disease. Eye abnormalities include anterior lenticonus, maculopathy,corneal endothelial vesicles, and recurrent corneal erosion. The hearing loss
develops gradually and is usually detectable during late childhood or earlyadolescence.
Prevalence of Alport syndrome is estimated at 1/50 000.
Alport syndrome is caused by mutations in COL4A3, COL4A4, and COL4A5 genes.
The disease is known to be inherited in an X-linked, autosomal recessive orautosomal dominant pattern.
Indications for genetic testing:
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2.
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4.

Confirmation of clinical diagnosis
Carrier testing for at-risk relatives
Genetic counseling
Prenatal diagnosis for known familial mutation

Aminoglycoside-Induced Deafness
Aminoglycosides are a group of pharmacologic agents that have been shown tohave toxic effects to the cochleovestibular system.
Cochlear toxicity can result in sensorineural hearing loss and dysequilibrium.
Hearing loss is bilateral and severe to profound, occurring within a few days toweeks after administration of any amount of an aminoglycoside antibiotic such as
gentamycin, tobramycin, amikacin, kanamycin, or streptomycin.
Predisposition to aminoglycoside, caused by aminoglycoside exposure is known
to be associated with pathogenic variants in the MT-RNR1 gene. Nonsyndromic
mitochondrial hearing loss and deafness is transmitted by maternal inheritance.
Indications for genetic testing:
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2.
3.
4.
5.

Determination of molecular genetic basis of nonsyndromic sensorineural
hearing loss
Define etiology of hearing loss after aminoglycoside therapy
Detection the carrier status of individuals with family history of maternallyinherited hearing loss with or without aminoglycoside therapy
Detection the carrier status of relatives with a known mutation
Genetic counselingBranchiootorenal Syndrome
Branchiootorenal (BOR) syndrome is characterized by malformations of the outer,middle, and inner ear associated with conductive, sensorineural, or mixed hearing
impairment, branchial arch anomalies (branchial clefts, fistulae, cysts), and renal
abnormalities. Renal malformations may include urinary tree malformation, renal
hypoplasia or agenesis, renal dysplasia, renal cysts. In some cases, end-stage
renal disease develops later in life.
BOR manifests wide clinical heterogeneity between affected individuals. Estimatedprevalence of the disease is 1/40,000.
BOR syndrome is transmitted in an autosomal dominant manner.
Indications for genetic testing:
1.
2.
3.

Confirmation of clinical diagnosis
Genetic counseling
Prenatal diagnosis for known familial mutation

Branchiootorenal Syndrome NGS-based test
details
NGS-based test covers the entire coding region of EYA1, SIX1, SIX5genes associated withbranchiootorenal syndrome.
Testing is available both with genotyping service (includes genotyping, electronic
copy of the results report) and diagnostic package service (includes DNA
extraction, detection of genetic variations, confirmation of disease associatedvariants by Sanger sequencing, biological and clinical interpretation of diseaseassociated variants, the results report by registered mail).
Turnaround Time:
Genotyping service
8 weeks
Diagnostic package service
12 weeks
Specimen Requirements:
2-4 ml of blood with anticoagulant EDTA
Send blood samples at room temperature. Blood samples can be preserved at
2-8°C before shipping. Blood samples are recommended not to freeze and not tostore longer than one week.
4 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
Send DNA samples at room temperature or frozen. To avoid sample loss andcontamination, please use 0,5-2,0 ml screw cap tubes, tubes with safe lock lid or
wrap the caps of each microtube with parafilm.
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose
gel as a single band, showing no degradation, alongside with a quantitative DNAmarker.

Jervell and Lange-Nielson Syndrome
Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital
profound bilateral sensorineural hearing loss and prolonged QT interval withventricular tachyarrhythmias. Cardiac events, which are primarily triggered bystress and exercise, may result in syncope or sudden death. 50% of individuals
become symptomatic before age of 3. Iron-deficient anemia and elevated levels ofgastrin are also frequent symptoms of JLNS.
JLNS is inherited in an autosomal recessive manner.
An estimated prevalence of disorder is 1.6 to 6 per 1 million. In Norway andSweden there are a higher prevalence, up to 1:200,000.
Indications for genetic testing:
1.
2.
3.
4.

Confirmation of clinical diagnosis
Testing of family members of the affected individuals
Carrier status detection of known mutation
Genetic counseling

Pendred Syndrome
Pendred syndrome is an autosomal recessive condition characterized by bilateral
sensorineural hearing impairment, vestibular and cochlear abnormalities, temporalbone abnormalities and goiter. Considerable phenotypic variability is found even
within the same family. Sensorineural hearing lossis usually congenital, severe toprofound and non-progressive. However, hearing loss may be later onset andprogressive in some patients.
Pendred syndrome, as well as nonsyndromic hearing loss and deafness(DFNB4) show similar phenotypic spectrum. DFNB4 is characterized bynonsyndromic sensorineural hearing loss, vestibular dysfunction, enlarged
vestibular aqueduct but normal thyroid function.
Indications for genetic testing:
1.
2.
3.

Confirmation of clinical diagnosis
Carrier status detection of known mutation
Genetic counselingSensorineural Hearing Loss
Hereditary sensorineural hearing loss (SNHL) includes syndromic and nonsyndromic forms. The syndromic forms of SNHL include Usher syndrome, Pendredsyndrome, Waardenburg syndrome, Jervell and Lange-Nielsen syndromes, etc.
Most cases of SNHL are nonsyndromic. SNHL can follow a pattern of autosomal
dominant, autosomal recessive, x-linked recessive, or mitochondrial inheritance.
Indications for genetic testing:
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2.
3.
4.
5.
6.
7.
8.

Confirmation of clinical diagnosis
Determination of molecular genetic basis both of nonsyndromic and/orsyndromic SNHLDistinguish different forms of nonsyndromic hearing loss and deafness
Define etiology of hearing loss after aminoglycoside therapy
Detection the carrier status of individuals with family history of maternallyinherited hearing loss with or without aminoglycoside therapy
Detection the carrier status of relatives with a known mutation
Genetic counseling
Prenatal diagnosis

Stickler Syndrome
Stickler syndrome is a group of hereditary conditions affecting connective tissue.
Stickler syndrome is characterized by ocular findings, distinctive facialabnormalities, hearing loss, skeletal abnormalities, and joint problems.
Eye findings may include high myopia, cataract, vitreoretinal or chorioretinaldegeneration, and retinal detachment. Hearing loss can be both conductive andsensorineural. Affected individuals have a characteristic flattened facial appearance
caused by midfacial underdevelopment and cleft palate.
Stickler syndrome is inherited in an autosomal dominant or autosomal recessive
manner. Stickler syndrome affects approximately 7,500 to 9,000 newborns.
Indications for genetic testing:
1.
2.
3.

Confirmation of clinical diagnosis
Carrier testing for at-risk family members
Genetic counseling

Treacher Collins Syndrome
Treacher Collins syndrome (TCS) is a congenital disorder characterized bycraniofacial deformities, external ear abnormalities, and eye anomalies. The mostcharacteristic features of TCS are micrognathia, conductive hearing loss, coloboma
of the lower eyelid, and absence of the lower eyelashes. Less common signs
include cleft palate and unilateral or bilateral choanal stenosis or atresia.
TCS affects an estimated 1 in 50,000 people. The disorder has an autosomaldominant pattern of inheritance. Approximately 1% of TCS is inherited in an
autosomal recessive manner.
Indications for genetic testing:
1.
2.
3.

Confirmation of clinical diagnosis
Carrier testing for at-risk family members
Genetic counseling

Waardenburg Syndrome
Waardenburg syndrome (WS) is a group of genetic conditions characterized bysensorineural hearing loss and pigmentary abnormalities of the iris, hair, and skin,along with dystopia canthorum. Hearing loss is congenital, typically nonprogressive, either unilateral or bilateral, and sensorineural.
The classic sign of hair pigmentation anomaly with WS is white forelock appearing
typically in the teen years. Ocular pigmentary manifestations may include completeor segmental heterochromia or hypoplastic or brilliant blue irides.
Waardenburg syndrome affects an estimated 1 in 20,000-40,000 people.
Four types of WS can be distinguished by physical characteristics and genetic
cause. Types I and III are inherited in an autosomal dominant manner, types II andIV are autosomal recessive.
Indications for genetic testing:
1.
2.
3.

Confirmation of clinical diagnosis
Carrier testing for at-risk relatives
Genetic counselingZellweger Spectrum Disorders
Zellweger spectrum of peroxisome biogenesis disorders comprises Zellweger
syndrome,neonatal adrenoleukodystrophy (NALD), and infantile Refsum
disease. These three diseases have overlapping clinical phenotypes. Zellweger
syndrome is considered to be the most severe form, NALD intermediate, andinfantile Refsum disease the least severe.
Onset of manifestations is usually in the newborn period or later in childhood andincludes hypotonia, seizures, distinctive craniofacial features (flattened facies, large
anterior fontanelle, widely split sutures, and broad nasal bridge), feeding difficulties,and liver dysfunction. Older children experience sensorineural hearing loss, retinal
dystrophy and developmental delays. Affected individuals may also have skeletal
abnormalities, adrenal insufficiency, episodes of hemorrhage and intracranial
bleeding, and coagulopathy.
The Zellweger spectrum disorders are inherited in an autosomal recessive
manner. The Zellweger spectrum disorders are estimated to occur in 1 in 50,000
individuals.
Indications for genetic testing:
1.
2.
3.
4.

Confirmation of clinical diagnosis
Carrier status detection of known mutation
Prenatal diagnosis for known familial mutation
Genetic counseling