This introductory information is not intended to replace a consultation with a healthcare provider. Please see NSGC.org or Find a Genetic Service - Find Genetic Clinics (acmg.net) to locate a Genetics healthcare provider near you.
Syndromic Hearing Loss occurs with other symptoms of medical importance. There are more than 400 syndromes that have been identified that include hearing loss.
Autosomal Dominant
Stickler Syndrome
Stickler Syndrome - GeneReviews® - NCBI Bookshelf (nih.gov)
- Hearing loss may be conductive, sensorineural, or mixed and may be progressive.
- Facial features may include small jaw (micrognathia) with cleft palate (Pierre Robin sequence), and flattened midface.
- The eyes and some forms of Stickler may have severe and progressive near-sightedness (myopia), cataracts, glaucoma, and retinal detachment.
- Other findings may include bone/joint disorders, early adult-onset arthritis, hyperflexibility, and middle ear bone (ossicular) malformations.
- Changes in six genes are known; all are related to altered expression of a collagen/connective tissue gene.
- Types IV, V, and VI are less common and are inherited as autosomal recessive conditions.
More about Stickler Syndrome
Waardenburg Syndrome
Waardenburg Syndrome - NORD (National Organization for Rare Disorders) (rarediseases.org)
- There are four broad types of Waardenburg syndrome with types I and II being the most common.
- Hearing loss is sensorineural and may be in one (unilateral) or both (bilateral) ears.
- Features may show pigmentary changes including premature graying hair, white forelock, two different-colored eyes (heterochromia irides, usually bright blue and brown eyes), and partial albinism.
- Facial features may include fused eyebrows (synophrys), widely spaced eyes (hypertelorism seen in Type I), high nasal bridge, and under-developed nose tip (hypoplastic alae nasi).
More about Waardenburg Syndrome
Branchio-Oto-Renal (BOR) Syndrome
- Hearing loss is conductive, sensorineural, or mixed.
- Ears commonly have structural changes in the outer, middle, or inner ear, and may show enlarged vestibular aqueducts.
- Face may have cysts (or pits), often in front of the ears (preauricular).
- Neck may have a cyst or sinus (branchial cleft).
- Renal (kidney) problems may be non-existent, mild, or even life threatening.
- Changes in at least two genes have been found to cause BOR Syndrome, with other genes being controversial.
More about Branchio-Oto-Renal Syndrome
CHARGE Syndrome
CHD7 Disorder - GeneReviews® - NCBI Bookshelf (nih.gov)
- Hearing loss may be conductive, sensorineural, or mixed and range from mild to profound.
- Four unique findings aiding in diagnosis are coloboma, choanal atresia, cranial nerve problems, and unusually shaped ears.
- CHARGE is mnemonic for
Colobomas (missing portion of the eye),
Heart defects,
Atresia (narrowing) of the choanae (the opening of the skull to the nose),
Retardation of growth and development,
Genital abnormalities, and
Ear changes.
- Changes in the CHD7 gene cause most cases.
More about CHARGE Syndrome
Treacher-Collins Syndrome
Treacher Collins Syndrome - GeneReviews® - NCBI Bookshelf (nih.gov)
- Hearing loss is conductive
- Striking facial features include under-developed cheek bones (malar hypoplasia), absent/malformed outer ears, absent (atresia) or narrow (stenosis) ear canals, skin tags in front of the ear (preauricular), notching (coloboma of the lower eyelids and absence of lower eyelashes)
- Occasional features include cleft palate or cleft lip and choanal (the opening of the skull to the nose) narrowing or blockage
- Changes in three genes are known to cause Treacher-Collins
More about Treacher-Collins Syndrome
Neurofibromatosis Type II (NFII)
Neurofibromatosis 2 - GeneReviews® - NCBI Bookshelf (nih.gov)
- Hearing loss is progressive, sensorineural sometimes resulting in deafness
- Both sides (bilateral) vestibular schwannomas (tumor) develop by 30 years of age.
- Other tumors may also grow
- Cataracts rarely cause vision problems but can aid in diagnosis
- Only one gene, NF2, is known to cause Neurofibromatosis Type II.
More about Neurofibromatosis Type II
Autosomal Recessive
Usher Syndrome
What Is Usher Syndrome? Symptoms & Treatment | NIDCD (nih.gov)
- Usher Syndrome is the most common type of autosomal recessive syndromic hearing loss.
- Usher Syndrome results in combined hearing and vision loss. However, not all variants in Usher Syndrome genes lead to both hearing loss and vision loss. Some pathogenic variants may result in only hearing or only vision loss.
- Type I
- Profound, sensorineural hearing loss present at birth (congenital)
- Little or no benefit from hearing aid use
- Vision loss is due to retinitis pigmentosa (RP) beginning with night-blindness by age 10 with loss of peripheral vision “tunnel vision.” Complete loss of vision is expected.
- Severe balance (vestibular) dysfunction problems
- Caused by multiple recessive gene pairs
Usher Syndrome Type I - GeneReviews® - NCBI Bookshelf (nih.gov)
- Type II
- Moderate to severe hearing loss present at birth (congenital)
- Downward-sloping, sensorineural hearing loss
- Vision loss is due to retinitis pigmentosa (RP) beginning with night-blindness after age 10 with loss of peripheral vision “tunnel vision”. Many people continue to have a small area of vision throughout their lives.
- No balance (vestibular) problems
- Caused by multiple recessive gene pairs
Usher Syndrome Type II - GeneReviews® - NCBI Bookshelf (nih.gov)
- Type III
- Normal hearing at birth
- Later onset of progressive, sensorineural hearing loss
- Vision loss is due to retinitis pigmentosa (RP) beginning with night-blindness with loss of peripheral vision “tunnel vision”. Onset and severity of vision loss varies
- Variable balance (vestibular) problem
- Caused by one recessive gene pair
Pendred Syndrome
Pendred Syndrome/Nonsyndromic Enlarged Vestibular Aqueduct - GeneReviews® - NCBI Bookshelf (nih.gov)
- One of the most common types of recessive syndromic hearing loss
- In most cases, hearing loss is sensorineural and may be progressive.
- Enlarged vestibular aqueduct is usually seen.
- Other inner ear malformations (Mondini malformation) may be present.
- Balance dysfunction is present in most cases.
- May be an associated enlarged thyroid gland (goiter)
More information about Pendred Syndrome from NIDCD
Jervell and Lange-Nielson Syndrome (JL-N)
Jervell and Lange-Nielsen (JLN) Syndrome - GeneReviews® - NCBI Bookshelf (nih.gov)
- Third most common type of recessive syndromic hearing loss
- Bilateral, profound sensorineural hearing loss is present at birth (congenital).
- The other major finding in JL-N is an abnormal heart rhythm (long Q-T), which could lead to fainting spells and possible sudden death.
- Abnormal heart rhythms may be successfully treated with medications.
- Mutations in two gene pairs are known to cause the condition.
More information about Jervell and Lange-Nielsen Syndrome
X-Linked (Sex-Linked)
Alport Syndrome
Alport Syndrome - GeneReviews® - NCBI Bookshelf (nih.gov)
- Hearing loss is progressive and sensorineural.
- Other features include kidney problems (nephritis), near-sightedness (myopia), or cataracts which typically do not cause vision loss.
- May be X-linked (due to an altered gene on the X chromosome), autosomal recessive or autosomal dominant depending on which gene is involved and the specific pathogenic variant or variants
More about Alport Syndrome
X-Linked Congenital Stapes Fixation with Perilymph Gusher
- Hearing loss in males is mixed and may be progressive.
- Female carriers may have mild, mixed or sensorineural hearing loss.
- Risk of further hearing loss if middle ear surgery is performed to correct the stapes fixation because the surgery may result in sudden loss of inner ear fluid (perilymph)
More about X-linked Congenital Stapes Fixation with Perilymph Gusher
Mitochondrial
Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)
- Some cases present with profound sensorineural hearing loss.
- Highly variable symptoms may include intermittent vomiting, limb weakness, stroke-like episodes, partial paralysis, partial blindness, seizures, migraine-like headaches, diabetes, short stature, heart problems and kidney problems.
www.ncbi.nlm.nih.gov/books/NBK1233/
Maternally Inherited Diabetes and Deafness (MIDD)
- Onset of hearing loss and diabetes type II is in mid-adulthood
- Hearing loss is sensorineural and often found in the high frequencies.
More about Maternally Inherited Diabetes and Deafness
Kearns-Sayre Syndrome (KSS)
- Onset of bilateral and sensorineural hearing loss generally before age 20
- Other findings include unsteady gait (ataxia), short stature, delayed puberty, progressive paralysis of the eye muscles (ophthalmoplegia), and progressive blindness (retinopathy).
More about Kearns-Sayre Syndrome
Myoclonic Epilepsy and Ragged Red Fibers (MERRF)
- Hearing loss is sensorineural of varying degree
- Other findings include unsteady gait (ataxia), epilepsy, and possible blindness (optic atrophy)
More about Myoclonic Epilepsy with Ragged-Red Fibers
