Klippel-Feil syndrome (KFS)

Definition

Klippel-Feil syndrome is a genetically determined anomaly of the cervical spine, including a reduction in the number and fusion of vertebrae. It is clinically manifested by visually detectable neck shortening, low location of the hair growth border on the back of the head, and restricted head movements. As a rule, Klippel-Feil syndrome is combined with other congenital anomalies of the skeleton and somatic organs. Diagnosis involves various subspecialists, radiography, CT and MRI of the spine, genetic analysis, and extended examination of internal organs (heart, kidneys, lungs, brain). Conservative treatment is carried out through massage, therapeutic gymnastics, and physiotherapy. Surgical treatment is possible – cervicalization surgery.

General information

Klippel-Feil syndrome is a congenital, genetically determined cervical spine pathology consisting of fusion (synostosis) and a reduced number of vertebrae. The most typical and permanent sign of the syndrome is a pronounced shortening of the neck, which is also referred to in medical practice as short neck syndrome. In most cases, it is combined with other anomalies of the musculoskeletal system (torticollis, scoliosis, Sprengel’s disease, hypoplasia of the upper limb, syndactyly) and congenital malformations of internal organs (kidneys, cardiovascular system, lungs). Klippel-Feil syndrome is a rare disease. Its incidence is approximately 1 case per 120,000 newborn children. 

Modern clinical neurology categorizes Klippel-Feil syndrome into three types. The first type – KFS1 – is characterized by reduced cervical vertebrae. Usually, a person has seven vertebrae in the cervical region; with KFS1, there are usually 4-5. The second type – KFS2 – is the synostosis of all cervical vertebrae, their fusion with the occipital bone and upper thoracic vertebrae. The third type – KFS3 – combines the first or second type with a fusion of vertebrae in the lower thoracic and lumbar regions. Often, there are extra ribs in the cervical region and spina bifida – non-union of the vertebral arches.

Causes

Klippel-Feil syndrome is a genetically determined pathology. Sporadic cases of the syndrome occur occasionally. The anomaly is formed intrauterine, while still in the embryonic period, due to hypo- and aplasia, impaired separation of cervical segments, and delayed fusion in the process of vertebral laying. 

The most studied gene is GDF6, which is responsible for the origin of KFS1. Mutations in this gene lead to impaired synthesis of a protein involved in the formation of the bone and joint apparatus by creating a distinction between individual bones. Depending on the type, Klippel-Feil syndrome has a different mechanism of inheritance: for KFS1 and KFS3, it is autosomal dominant, and for KFS2, it is autosomal recessive.

Symptoms

The main clinical triad characterizing Klippel-Feil syndrome is a shortening of the neck, displacement of the hair growth border down the back of the neck, and impaired spine mobility in the cervical region. The severity of neck shortening may vary; in the most severe variant, earlobes reach the shoulders and the chin – the sternum, swallowing, and breathing are difficult. Wide separation of the shoulder blades and often their shortening is characteristic. There may be typical symptoms of Sprengel’s disease, such as high standing of one of the shoulder blades. In some cases, the musculature of the shoulder girdle and neck folds are abnormalities. In rare cases, there is a radicular syndrome – pain associated with compression of the cervical spinal roots.

In 50-60% of cases, Klippel-Feil syndrome is combined with scoliosis, and in 25% of cases, with a bony variant of torticollis. Short neck syndrome may be combined with upper limb anomalies (polydactyly, syndactyly, congenital amputations), foot deformities, rib malformations, dental anomalies, facial asymmetry, and hyperopia. Dystopia, aplasia, or hypoplasia of the kidneys is diagnosed in 45% of patients, and hydronephrosis and ureteral ectopia are possible. Congenital deafness is detected in 25% of patients, wolf’s mouth in 20%, and congenital heart defects in 15% (patentductus arteriosus, atrial and ventricular septal defects, congenital aortic dextroposition). Aplasia or hypoplasia of the lungs may be observed.

The nervous system can be oligophrenia (mental retardation), epilepsy, hydrocephalus, spinal hernia, microcephaly, or oculomotor disorders (strabismus, ptosis, Horner syndrome). From an early age, it is characterized by muscle weakness in the limbs and synkinesia – involuntary simultaneous movements of both hands, more often only the hands. Over time, spastic and flaccid paraparesis and tetraparesis may occur.

Diagnosis

The diagnosis is verified based on the typical triad of signs observed since birth, examination data, family history, and results of instrumental and genetic studies. Klippel-Feil syndrome with a detailed indication of associated anomalies can only be established through the joint work of many specialized specialists: neurologist, orthopedist, geneticist, cardiologist, nephrologist, pulmonologist, and ophthalmologist.

First of all, radiography of the cervical spine in 2 projections is performed. In KFS1, radiographs in most cases show complete synostosis of 4-5 vertebrae into a single poorly differentiated conglomerate. In some cases, there are narrow light strips between the vertebrae, corresponding to underdeveloped discs, indicating partial synostosis, which, as the child grows, leads to curvature of the spine. Klippel-Feil type II syndrome is radiologically characterized by a combination of synostosis of the seven cervical vertebrae with atlas assimilation and fusion of the upper thoracic vertebrae. To rule out KFS3, thoracic and lumbar spine radiography is performed.

CT of the spine provides more complete information on bony anomalies. However, its use in early childhood is limited due to the accompanying radiation exposure. If necessary, a spine MRI may be performed to assess the condition of soft tissue structures of the affected area (roots, spinal cord). Klippel-Feil syndrome should be differentiated from congenital muscular torticollis and spinal tuberculosis.

The diagnostic algorithm also includes an examination of internal organs: neurosonography, brain MRI, abdominal ultrasound, cardiac ultrasound, ECG, renal ultrasound or CT scan, excretory urography, and chest radiography. Genetic counseling with genealogical tree analysis and DNA testing is provided.

Treatment of Klippel-Feil syndrome

Conservative therapeutic measures aimed at preventing the development of spinal deformities and increasing the volume of movement in the neck are carried out mainly. Massage of the cervical and collar zone, shoulder girdle, and upper extremities is performed. Regular physical therapy sessions are recommended. It is possible to use physiotherapy. If indicated, symptomatic treatment of disorders in the work of somatic organs is carried out. In radicular pain, prescribe analgesics and wear a Shantz collar.

Persistent pain syndrome due to root compression by the upper ribs is an indication of surgery. The surgical intervention is performed according to the Bonol technique and represents the so-called cervicalization by resection of the upper four ribs. Access is through a paravertebral incision parallel to the inner edge of the scapula. The operation is performed in 2 stages, separately on each side.

All these treatment options are available in more than 770 hospitals (https://doctor.global/results/diseases/klippel-feil-syndrome-kfs). For example, Cervical fusion can be performed in these countries for following approximate prices:

Turkey $6.0 K in 31 clinics

China $18.8 K in 9 clinics

Germany $20.1 K in 43 clinics

Israel $22.8 K in 17 clinics

United States $30.2 K – 132.9 K in 19 clinics.

Prognosis

Klippel-Feil syndrome itself has a favorable vital prognosis. The presence of malformations of somatic organs significantly complicates the situation and may cause premature death. In functional terms, the prognosis is unfavorable; despite conservative measures, patients still have a marked restriction of head movements, the degree of which depends on the type and severity of the syndrome. The course of the disease may be aggravated by degenerative changes occurring in the spine.