Rare Neurology News

Disease Profile

Klippel Feil syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q76.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cervical vertebral fusion

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

Klippel Feil syndrome (KFS) is a condition affecting the development of the bones in the spine. People with KFS are born with abnormal fusion of at least two spinal bones (vertebrae) in the neck. Common features may include a short neck, low hairline at the back of the head, and restricted movement of the upper spine. Some people with KFS have no symptoms. Others may have frequent headaches, back and neck pain, and other nerve issues. People with KFS are at risk for severe spinal injury. KFS can occur along with other types of birth defects, and sometimes KFS occurs as a feature of another disorder or syndrome. The cause of most cases of KFS is unknown, but sometimes it is caused by genetic alterations (mutations) in one of several different genes. This condition is diagnosed based on a clinical examination, the symptoms, and imaging studies. Treatment is symptomatic and may include medications, surgery, and/or physical therapy.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Klippel-Feil syndrome (KFS). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list also does not include every symptom or feature that has been described in this condition.

Symptoms of KFS may include:[3][4]

  • Fusion of 2 or more spinal bones in the neck (cervical vertebrae).
  • Low hairline at the back of the head
  • Short neck
  • Limited neck range of motion
  • Scoliosis (curvature of the spine)
  • Sprengel deformity (abnormality of the shoulder blade)
  • Central nervous system abnormalities (including Chiari malformation, spina bifida, or syringomyelia), and/or neurological symptoms
  • Other skeletal abnormalities (including those of the ribs, limbs and/or fingers)

People with KFS may have headaches, muscle and nerve pain, or other neurological problems. There is an increased risk for narrowing of the spine (spinal stenosis) and serious spinal injury after mild trauma. Some people with KFS have few or no symptoms.[2][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal vertebral segmentation and fusion
0005640
Cervical C2/C3 vertebral fusion
0004602
Facial asymmetry
Unsymmetrical face
Crooked face
Asymmetry of face

[ more ]

0000324
Limited neck range of motion
0000466
Low posterior hairline
Low hairline at back of neck
0002162
Short neck
Decreased length of neck
0000470
Webbed neck
Neck webbing
0000465
30%-79% of people have these symptoms
Abnormal shoulder morphology
Abnormality of the shoulder
0003043
Abnormality of the ribs
Rib abnormalities
0000772
Congenital muscular torticollis
0005988
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Scoliosis
0002650
Sprengel anomaly
High shoulder blade
0000912
5%-29% of people have these symptoms
Abnormal cranial nerve morphology
0001291
Abnormal sacrum morphology
0005107
Abnormality of limb bone morphology
Abnormal shape of limb bone
Arm and/or leg bone differences
Limb abnormality

[ more ]

0002813
Anal atresia
Absent anus
0002023
Cleft palate
Cleft roof of mouth
0000175
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Ectopic anus
Abnormal anus position
0004397
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Posterior fossa cyst
0007291
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney

[ more ]

0008678
Spina bifida
0002414
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
1%-4% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Bimanual synkinesia
Hand mirror movements
Mirror hand movements
Mirror movements

[ more ]

0001335
Mixed hearing impairment
Hearing loss, mixed
Mixed hearing loss

[ more ]

0000410
Unilateral renal agenesis
Absent kidney on one side
Missing one kidney
Single kidney

[ more ]

0000122
Percent of people who have these symptoms is not available through HPO
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears

[ more ]

0000377
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Cervicomedullary schisis
0030325
Cleft upper lip
Harelip
0000204
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Fused cervical vertebrae
Fused neck
0002949
Sensorineural hearing impairment
0000407
Variable expressivity
0003828

Cause

The exact underlying causes and mechanisms of Klippel Feil syndrome (KFS) are not well understood. Most cases of isolated KFS (meaning not associated with another syndrome) are sporadic, meaning there is no known family history or obvious genetic cause.[4] It is thought that KFS is likely caused by a combination of genetic and environmental factors.

In some people, genetic alterations (mutations) in at least three genes have been linked to KFS: GDF6GDF3 and MEOX1.[1][4]

Diagnosis

Klippel Feil syndrome (KFS) is typically diagnosed based on a clinical examination, symptoms and imaging studies (X-rays, MRI or CT scan). Additional studies may be necessary to look at other parts of the skeleton and other body systems. Some people with KFS have few or no symptoms, and are diagnosed by chance after having imaging studies for some other reason.[1][2]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for Klippel-Feil syndrome (KFS) is generally based on the symptoms. Management depends on the features and severity in each person, and may be lifelong. Some people with KFS require activity restriction, while others may require surgery. 

    Some of specialists involved in the care of someone with KFS may include:[1][2][3]

    • Neurologist
    • Neurosurgeon
    • Orthopedic surgeon
    • Pain management specialist
    • Physical therapist

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

            In-Depth Information

            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
              Klippel Feil syndrome, Autosomal dominant
              Klippel Feil syndrome, Autosomal recessive
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Klippel Feil syndrome. Click on the link to view a sample search on this topic.

              References

              1. Frikha R. Klippel-Feil syndrome: a review of the literature. Clin Dysmorphol. 2020; 29(1):35-37. https://pubmed.ncbi.nlm.nih.gov/31577545.
              2. Menger RP, Notarianni C. Klippel Feil Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2020; https://pubmed.ncbi.nlm.nih.gov/29630209.
              3. Zhou PL, Poorman GW, Wang C, Pierce KE, Bortz CA et al.. Klippel-Feil: A constellation of diagnoses, a contemporary presentation, and recent national trends.. J Craniovertebr Junction Spine. 2019; 10(3):133-138. https://pubmed.ncbi.nlm.nih.gov/31772424.
              4. Klippel-Feil Syndrome. National Organization for Rare Disorders (NORD). Updated 2019; https://rarediseases.org/rare-diseases/klippel-feil-syndrome/.
              5. Gruber J, Saleh A, Bakhsh W, Rubery PT, Mesfin A. The Prevalence of Klippel-Feil Syndrome: A Computed Tomography-Based Analysis of 2,917 Patients. Spine Deform. 2018; 6(4):448-453. https://pubmed.ncbi.nlm.nih.gov/29886918.

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