Wildervanck Syndrome

Disease Overview

Wildervanck syndrome, also known as cervicooculoacoustic syndrome, is a rare genetic disorder that primarily affects females. The disorder is characterized by a skeletal condition known as Klippel-Feil syndrome (KFS); abnormalities of certain eye (ocular) movements (i.e., Duane syndrome); and/or hearing impairment that is present at birth (congenital). In individuals with KFS, there is abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Duane syndrome is characterized by limitation or absence of certain horizontal eye movements; retraction or “drawing back” of the eyeball into the eye cavity (orbit) upon attempting to look inward; and, in some people, abnormal deviation of one eye in relation to the other (strabismus). In some affected individuals, additional physical abnormalities may also be present. In most people, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically).

• View Full Report Show Less
• Print / Download as PDF

• Next section >

• < Previous section
• Next section >

Synonyms

• cervico-oculo-acoustic syndrome
• COA syndrome

• < Previous section
• Next section >

• < Previous section
• Next section >

Signs & Symptoms

Wildervanck syndrome can present with a wide range of symptoms, and not all individuals will have the same issues.  Usually, Wildervanck syndrome is characterized by three main findings (however, not everyone with Wildervanck syndrome has all three of these symptoms):

• Fusion of bones in the neck (Klippel-Feil syndrome): This means two or more bones of the spine (vertebrae) are fused together, leading to a short neck and limited movement
• Eye movement problems (Duane syndrome): This affects the ability to move the eyes properly, usually causing difficulty moving the eyes inward, outward, or both. It may affect one or both eyes and may include a narrow space between the eyelids and retraction of the eyeball into the eye socket when trying to look inward, as well as strabismus (lazy eyes) which can be one eye that deviates inward (convergent strabismus) or outward (divergent strabismus) compared to the other
• Hearing loss at birth: Hearing problems can affect one or both ears and may involve difficulty with sound transmission (conductive hearing loss) or damage to the inner ear (sensorineural hearing loss) or both

Researchers have identified three subtypes of Klippel-Feil syndrome (KFS) in Wildervanck syndrome:

• KFS type I: Extensive fusion of the neck and upper back vertebrae
• KFS type II: Fusion in one or two vertebrae in the neck or upper back, often along with malformations in half of certain vertebrae (hemivertebrae)
• KFS type III: Fusion of vertebrae in the neck, as well as vertebrae in the upper or lower back

People with KFS may have an unusually short neck. In severe cases, the head may appear to sit directly on the body. This condition can limit head and neck movement and cause a low hairline at the back of the head that may extend to the shoulders. The face might appear uneven from one side to the other (facial asymmetry) and the neck may be twisted (torticollis) with the head tilted to one side.

There is also a risk of neurological complications from unstable vertebrae in the neck, which could cause spinal cord injury either spontaneously or after minor trauma. These complications might include:

• Pain
• Unusual sensations like tingling or prickling
• Increased reflexes
• Weakness or paralysis on one side of the body (hemiplegia) or in the legs (paraplegia)

Other signs and symptoms may include:

• Additional skeletal issues such as:
  • Spina bifida, an incomplete development of the spine, which can leave part of the spinal cord exposed
  • Scoliosis: An abnormal lateral curvature of the spine
  • Sprengel deformity: A condition where the shoulder blade is higher than normal and underdeveloped, which may limit arm movement, and, in some people, there is a lump at the base of the neck due to the raised shoulder blade
• Additional eye problems including:
  • Swelling of the optic disc (the “blind spot”) in the eye (pseudopapilledema) presenting from birth for unknown reasons
  • Blepharoptosis, the dropping of the upper eyelids which narrows the space between the eyelids (palpebral aperture)
  • Partial dislocation of the lenses in both eyes
  • Cysts on the eyeballs (epibulbar dermoids and lipodermoids)
• Facial differences such as:
  • Cleft palate (incomplete closure of the roof of the mouth)

• • Preauricular skin tags or pits which are extra pieces of skin or small holes in front of the ears
• Kidney defects
• Cranial abnormalities that may include:
  • Small head (microcephaly)
  • Hydrocephalus, a condition where fluid builds up in the brain due to blocked flow or poor absorption of cerebrospinal fluid, leading to increased pressure in the brain
  • Occipital meningocele, which is a protrusion of the membranes surrounding the brain through a defect in the skull
• Gallstones, the presence of solid lumps within the gallbladder (cholelithiasis)

• Heart and vascular problems including:
  • Congenital heart defects such as:
  • Atrial or ventricular septal defects, holes in the walls that separate the chambers of the heart
  • Aortic valve fenestration which are small holes in the heart valves
  • Coronary artery aneurysms which are enlarged arteries from the heart
  • Vertebral artery dissection, a tear in the arteries of the spine
  • Other vascular malformations that may include the presence of only one coronary artery or a persistent left superior vena cava, a vein that normally disappears before birth.

While most individuals with Wildervanck syndrome have normal intelligence, intellectual disability has been reported in some patients. Additionally, some people with the syndrome may have short stature, and one person was diagnosed with a growth hormone deficiency.

• < Previous section
• Next section >

• < Previous section
• Next section >

Causes

In most patients, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically).

According to other researchers, Wildervanck syndrome may result from the interaction of several different genes (polygenic inheritance), possibly in combination with certain environmental factors (multifactorial inheritance) with limitation to females.

There is a report in the medical literature describing one affected person who had a small loss (deletion) of a region located at the short arm (p) of the chromosome X (the Xp26.3 region) and others have suggested that it may be caused by changes (variants) in the FGF13 gene.

Because the disorder primarily affects females, some researchers suggest that Wildervanck syndrome may be transmitted in an X-linked dominant pattern. X-linked dominant disorders are caused by a disease-causing gene variant on the X chromosome and mostly affect females. Females are affected when they have an X chromosome with the gene variant. Males with a disease-causing gene variant for an X-linked dominant disorder are more severely affected than females and often do not survive.

• < Previous section
• Next section >

• < Previous section
• Next section >

Affected populations

Since the disorder was originally described in 1952 (L.S. Wildervanck), almost 90 patients have been reported in medical literature. As mentioned above, Wildervanck syndrome primarily affects females. According to some reports, approximately one percent of females with hearing impairment may be affected by Wildervanck syndrome.

• < Previous section
• Next section >

• < Previous section
• Next section >

Disorders with Similar Symptoms

Symptoms of the following disorders may be similar to those of Wildervanck syndrome. Comparisons may be useful for a differential diagnosis:

Duane syndrome: While Duane syndrome can be a feature of Wildervanck syndrome it can occur by itself. It is an eye movement disorder present at birth (congenital) characterized by horizontal eye movement limitation, a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction) or in both directions. Duane syndrome is considered a type of strabismus and subtype of the now termed congenital cranial dysinnervation disorders (CCDDs). The CCDDs are a group of congenital neuromuscular diseases resulting from developmental errors in innervation; the abnormalities involve one or more cranial nerves/nuclei with absence of normal innervation and/or secondary aberrant innervation. Duane syndrome has been subdivided clinically into three types: type 1, type 2 and type 3.

Klippel-Feil syndrome (KFS): While it can be part of Wildervanck syndrome it can occur by itself. The disorder is present at birth (congenital), but mild cases may go undiagnosed until later during life when symptoms worsen or first become apparent. In some individuals, KFS can be associated with a variety of additional symptoms and in these cases, it is even more difficult to differentiate from Wildervanck syndrome. KFS may also occur as part of other syndromes. Researchers have determined that some cases of KFS are associated with variants of the GDF6, GDF3, MEOX1 or MYO18B genes.

Oculo-auriculo-vertebral spectrum (OAVS) refers to three rare disorders that many clinicians believe to be related to one another, and which represent the range of severity of the same disorder. As the name suggests, they involve malformations of the eyes, ears and spine. Oculo-auriculo-vertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome presents frequently as the most severe form. Hemifacial microstomia appears to be an intermediate form. The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from person to person. However, such abnormalities tend to involve the cheekbones, jaw, mouth, ears, eyes and/or bones of the spinal column (vertebrae).  In most people, only one side of the body is affected (unilateral), but in about 10% to 33% both sides of the body (bilateral) are affected.

There are additional disorders that may be characterized by skeletal, ocular, auditory, or other abnormalities like those potentially associated with Wildervanck syndrome. (For more information on such disorders, choose the exact disease name as your search term in the Rare Disease Database.)

• < Previous section
• Next section >

• < Previous section
• Next section >

Diagnosis

Wildervanck syndrome may be detected at birth or during the first year of life based upon a thorough clinical evaluation, identification of characteristic physical findings and specialized tests. Diagnostic studies may include advanced imaging techniques, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. An MRI uses a magnetic field and radio waves to form detailed cross-sectional images of certain organs and tissues. Such techniques may help to detect and characterize abnormalities of the inner ear, union or fusion of certain bones of the spinal column (e.g., cervical vertebrae), possible impingement of vertebrae on the spinal cord, or other abnormalities potentially associated with the disorder.

In addition, in some individuals with Wildervanck syndrome, exploratory surgery may be conducted to detect malformations of the middle ear (exploratory tympanotomy). Additional specialized tests may also be performed to confirm or characterize other abnormalities that may be associated with the disorder (such as certain ocular findings, congenital heart defects, renal abnormalities, etc.).

Because of publications showing a possible relationship with variants in certain genes, it may be useful to have genetic testing.

• < Previous section
• Next section >

• < Previous section
• Next section >

Standard Therapies

Treatment
The treatment of Wildervanck syndrome is directed toward the specific symptoms and physical findings that are present in each individual. Such therapies may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child’s treatment. These may include pediatricians; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); eye specialists (ophthalmologists); hearing specialists (e.g., otologists and audiologists); physicians who diagnose and treat heart abnormalities (cardiologists); surgeons and/or other health care professionals.

Because some affected individuals with abnormal union or fusion of certain cervical vertebrae may have an increased risk of neurological complications, they should be regularly monitored by physicians. In addition, they should avoid activities that may lead to trauma or injury to cervical vertebrae.

In some individuals with Wildervanck syndrome, treatment measures may include surgical repair of certain abnormalities. For example, middle ear surgery may be recommended for some individuals with conductive hearing loss. Ocular surgery may help to improve or correct impairment of certain eye movements. In addition, for those with cervical spinal cord compression, surgery may be conducted to correct such compression or associated vertebral instability. Surgical measures may also be recommended for other skeletal, ocular, auditory, cardiac, or other abnormalities potentially associated with Wildervanck syndrome. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptomsand other factors.

In addition, some affected individuals with hearing impairment may benefit from the use of specialized hearing aids. Other treatment for Wildervanck syndrome is symptomatic and supportive.

In some children, early intervention may be important in ensuring that child with Wildervanck syndrome reaches their potential. Special services that may be beneficial include special education, physical therapy and/or other medical, social, and/or vocational services. Genetic counseling may be helpful for individuals with Wildervanck syndrome and their families.

• < Previous section
• Next section >

• < Previous section
• Next section >

Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

• < Previous section
• Next section >

• < Previous section
• Next section >

References

JOURNAL ARTICLES
Chima-Galán MDC, Sánchez-Beltrán NA, García-Ortiz L. Wildervanck syndrome: clinical case report. Arch Argent Pediatr. 2023 Jun 1;121(3):e202202624. English, Spanish.  https://www.sap.org.ar/docs/publicaciones/archivosarg/2023/v121n3a04e.pdf

Abu-Amero KK, Kondkar AA, Alorainy IA, et al. Xq26.3 microdeletion in a male with Wildervanck Syndrome. Ophthalmic Genet. 2014;35(1):18-24. doi:10.3109/13816810.2013.766218

Kumar A, Sahu A, Shetty S, Vijayalakshmi P. Wildervanck syndrome associated with cleft palate and short stature. Indian J Ophthalmol. 2010 Jul-Aug;58(4):323-5.

Dirik E, Yis U, Dirik MA, Cakmakçi H, Men S. Vertebral artery dissection in a patient with Wildervanck syndrome. Pediatr Neurol. 2008 Sep;39(3):218-20.

Oe K, Mori K, Konno T, Yoneda T, Ueyama K, Yamagishi M. Ruptured aneurysm of the sinus of Valsalva with Wildervanck syndrome (cervico-oculo-acoustic syndrome), blepharoptosis and short stature: case report. Circ J. 2007 Sep;71(9):1485-7.

Tubbs RS, Oakes WJ, Blount JP. Isolated atlantal stenosis in a patient with idiopathic growth hormone deficiency, and Klippel-Feil and Duane’s syndromes. Childs Nerv Syst. 2005 May;21(5):421-4. Epub 2004 May 7.

Balci S, Oguz KK, Firat MM, Boduroglu K. Cervical diastematomyelia in cervico-oculo-acoustic (Wildervanck) syndrome: MRI findings. Clin Dysmorphol. 2002 Apr;11(2):125-8.

Imaizumi K. [Wildervanck (cervico-oculo-acoustic) syndrome]. Ryoikibetsu Shokogun Shirizu. 2001;(33):361-2.

Smith SD, et al. Single gene influences on radiologically-detectable malformations of the inner ear. J Commun Disord. 1998;31:391-408.

Wang Y, et al. Wildervanck or cervico-oculo-acoustic syndrome. Lin Chuang Erh Pi Yen Hou Ko Tsa Chih. 1997;11:499-501.

Kumar A, et al. Wildervanck syndrome. Australas Radiol. 1996;40:160-161.

Johnson NA, et al. Wildervanck’s syndrome presenting as hemiparesthesia. Mil Med. 1995;160:208-211.

Kose G, et al. Cholelithiasis in cervico-oculo-acoustic (Wildervanck’s) syndrome. Acta Paediatr. 1993;82:890-891.

Gupte G, et al. Wildervanck syndrome (cervico-oculo-acoustic syndrome). J Postgrad Med. 1992;38:180-182.

Hughes PJ, et al. Wildervanck or cervico-oculo-acoustic syndrome and MRI findings. J Neurol Neurosurg Psychiatry. 1991;54:503-504.

Corsello G, et al. Cervico-oculo-acusticus (Wildervanck’s) syndrome: a clinical variant of Klippel-Feil sequence? Klin Padiatr. 1990;202:176-179.

• < Previous section
• Next section >

• < Previous section

Programs & Resources

• Assistance Programs
• Patient Organizations
• More Information

RareCare^® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Learn more about Patient Assistance Programs >

• < Previous section