Some science behind the scenes

Klippel-Feil syndrome

Klippel–Feil syndrome is a rare disease, initially reported in 1912 by Maurice Klippel and André Feil from France, characterized by the congenital fusion of any two of the seven cervical vertebrae. The syndrome occurs in a heterogeneous group of patients unified only by the presence of a congenital defect in the formation or segmentation of the cervical spine. Klippel-feil results in limited movement of the neck. Klippel–Feil syndrome is sometimes identified by shortness of the neck, but not all people with this disorder have a visibly shortened neck. Some people with the syndrome have a very low hairline. In 1919, André Feil in his PhD thesis, suggested another classification of the syndrome encompassing not only deformation of the cervical spine but also deformation of the lumbar and thoracic spine.

Numerous associated abnormalities of other organ systems may be present. This heterogeneity requires comprehensive evaluation of all patients and treatment regimes that can vary from modification of activities to extensive spinal surgeries. Furthermore, it is unclear whether Klippel–Feil syndrome is a unique disease, or if it is one part of a spectrum of congenital spinal deformities. Klippel–Feil syndrome is usually diagnosed after birth.

Although the actual occurrence for the KFS syndrome is unknown, it is estimated to occur 1 in 40,000 to 42,000 newborns worldwide. In addition, females seem to be affected slightly more often than males.

Genetics

Genetic genealogy has identified a specific location of a gene on a chromosome for Klippel-Feil Syndrome.

 Mutations in the GDF6 and GDF3 genes have been linked with the disease, however,  some people with Klippel–Feil syndrome do not have identified mutations in the GDF6 or GDF3 genes. In this case, the cause of the condition in these individuals is unknown.

GDF6 and GDF3 genes provide the body with instructions for making proteins involved in regulating the growth and maturation of bone and cartilage. These proteins actively regulate cell growth in embryonic and adult tissue. GDF6 specifically is involved in the formation of vertebral bones, among others, and establishing boundaries between bones in skeletal development while GDF3 is involved with bone and cartilage growth.

Mutations cause reductions in these functional proteins “but, it is unclear exactly how a shortage in these proteins leads to incomplete separation of the vertebrae in people with Klippel–Feil syndrome.”

When the GDF6 gene was knocked out in mice, the result was the fusion of bones

“Only by identifying the link between the genetic etiology and the phenotypic pathoanatomy of Klippel–Feil syndrome will we be able to rationalize the heterogeneity of the syndrome.”