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Klippel-Feil Syndrome

Updated : February 22, 2024





Background

Klippel-Feil syndrome is a complex disorder characterized by improper fusion of cervical vertebrae at C2 and C3, resulting from a failure in the normal segmentation or division of the cervical spine vertebrae during the early stages of fetal development.

This syndrome is distinguished by a low hairline, facial asymmetry, restricted neck motion, and a short neck. The anomalies can cause persistent headaches, a restricted range of motion in the neck, and pain in the neck musculature.

Unlike these comparatively milder symptoms, it can also cause some severe symptoms such as:

  • Neurological deficits
  • Spinal Stenosis
  • Cervical spine instability and deformity

Individuals can also present with multiple symptoms at once.

Epidemiology

Klippel-Feil syndrome was initially documented in 1912 by Andre Feil and Maurice Klippel. This syndrome occurs in roughly 1 in 40,000 to 42,000 infants globally and is slightly more common in girls.

A 2% incidence of this condition was observed on an MRI in a global population sample of 458 individuals. In another study by Brown et.al 1400 skeletons were reviewed, and the incidence was observed to be 0.71%.

It is vital to realize that asymptomatic pediatric patients, who do not receive cervical MRI and do not present with a physical deformity, will probably go undiagnosed into their adulthood.

Anatomy

Pathophysiology

Etiology

The etiology of this syndrome is still not definite. According to several studies, it has been hypothesized that the following factors are generally responsible:

  • Genetic factors
  • Primary neural tube complications
  • Vascular disruption
  • Global fetal insult

Other complications generally accompanied by this condition include:

  • Sprengel deformity
  • Fetal alcohol syndrome
  • Goldenhar syndrome

Some familial mutations in the MEOX1, GDF3, and GDF6 genes are known to cause this condition. The GDF6 gene is involved in bone development and the GDF3 gene is involved in the formation of bones.

Additionally, the MEOX1 gene causes the production of the homeobox protein MOX1 — which regulates vertebral separation. GDF6 and GDF3 anomalies are dominantly inherited, whereas MEOX1 mutations are recessively inherited.

Genetics

Prognostic Factors

Symptoms are more common with Klippel-Feil syndrome patients who have a spinal fusion above C3. The prognosis of this disease is associated with the degree of its severity, classified by the Samartzis classification system.

Type I means a single-level congenital fusion of the cervical segment. Type II includes multiple, non-contiguous congenitally fused segments, and Type III patients have multiple, contiguous congenitally fused segments in the cervical region.

In this study, it was noted that over 8 years, only 1/3rd of patients had symptoms. Individuals with a type-I deformity presented with axial symptoms, and the those with type II and III developed radiculopathy and myelopathy.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK493157/

Klippel-Feil Syndrome

Updated : February 22, 2024




Klippel-Feil syndrome is a complex disorder characterized by improper fusion of cervical vertebrae at C2 and C3, resulting from a failure in the normal segmentation or division of the cervical spine vertebrae during the early stages of fetal development.

This syndrome is distinguished by a low hairline, facial asymmetry, restricted neck motion, and a short neck. The anomalies can cause persistent headaches, a restricted range of motion in the neck, and pain in the neck musculature.

Unlike these comparatively milder symptoms, it can also cause some severe symptoms such as:

  • Neurological deficits
  • Spinal Stenosis
  • Cervical spine instability and deformity

Individuals can also present with multiple symptoms at once.

Klippel-Feil syndrome was initially documented in 1912 by Andre Feil and Maurice Klippel. This syndrome occurs in roughly 1 in 40,000 to 42,000 infants globally and is slightly more common in girls.

A 2% incidence of this condition was observed on an MRI in a global population sample of 458 individuals. In another study by Brown et.al 1400 skeletons were reviewed, and the incidence was observed to be 0.71%.

It is vital to realize that asymptomatic pediatric patients, who do not receive cervical MRI and do not present with a physical deformity, will probably go undiagnosed into their adulthood.

The etiology of this syndrome is still not definite. According to several studies, it has been hypothesized that the following factors are generally responsible:

  • Genetic factors
  • Primary neural tube complications
  • Vascular disruption
  • Global fetal insult

Other complications generally accompanied by this condition include:

  • Sprengel deformity
  • Fetal alcohol syndrome
  • Goldenhar syndrome

Some familial mutations in the MEOX1, GDF3, and GDF6 genes are known to cause this condition. The GDF6 gene is involved in bone development and the GDF3 gene is involved in the formation of bones.

Additionally, the MEOX1 gene causes the production of the homeobox protein MOX1 — which regulates vertebral separation. GDF6 and GDF3 anomalies are dominantly inherited, whereas MEOX1 mutations are recessively inherited.

Symptoms are more common with Klippel-Feil syndrome patients who have a spinal fusion above C3. The prognosis of this disease is associated with the degree of its severity, classified by the Samartzis classification system.

Type I means a single-level congenital fusion of the cervical segment. Type II includes multiple, non-contiguous congenitally fused segments, and Type III patients have multiple, contiguous congenitally fused segments in the cervical region.

In this study, it was noted that over 8 years, only 1/3rd of patients had symptoms. Individuals with a type-I deformity presented with axial symptoms, and the those with type II and III developed radiculopathy and myelopathy.

https://www.ncbi.nlm.nih.gov/books/NBK493157/