SNP Shot: Genomic Insights

Klippel-Feil syndrome (KFS) is a congenital skeletal condition characterized by the fusion of two or more vertebrae in the neck, present at birth. This fusion leads to a combination of features, most commonly a short neck, a hairline that appears low at the back of the head, and restricted neck movement. However, many individuals with KFS exhibit only one or two of these signs, and less than half display all three.

The fused vertebrae in KFS can limit neck and back mobility and cause chronic headaches and muscle pain of varying intensity in the neck and back. Individuals with fewer fused vertebrae generally experience fewer complications compared to those with more extensive fusion. Facial asymmetry, a slight difference in the size and shape of the face's sides, can also result from the shortened neck. Spinal trauma, like falls or accidents, can worsen existing problems in the fused area. Nerve damage in the head, neck, or back can occur due to vertebral fusion. Spinal stenosis, the narrowing of the spinal canal in the neck, may develop over time, potentially compressing and damaging the spinal cord. Less commonly, nerve abnormalities may result in unusual sensations or involuntary movements. Osteoarthritis, a painful joint condition, can develop around the fused vertebrae, or individuals may experience cervical dystonia, characterized by painful, involuntary neck muscle contractions. Besides the cervical fusion, other vertebral abnormalities are possible. Scoliosis, an abnormal curvature of the spine, is common in KFS due to vertebral malformation, and fusion may extend to vertebrae below the neck.

Beyond spine-related issues, KFS can present with diverse other features. Hearing impairment, eye abnormalities, cleft palate, genitourinary problems (such as kidney or reproductive organ abnormalities), heart defects, and lung defects leading to breathing difficulties are observed in some individuals. Other skeletal defects, like limb length discrepancies causing hip or knee misalignment, can also occur. Sprengel deformity, where shoulder blades are underdeveloped and abnormally high on the back, is another possible finding. Rarely, structural brain abnormalities or neural tube defects can occur.

Sometimes, KFS is part of a larger syndrome, such as Wildervanck syndrome or hemifacial microsomia. In these cases, individuals exhibit symptoms of both KFS and the co-occurring disorder.

Inheritance:

KFS caused by mutations in the GDF6 or GDF3 genes follows an autosomal dominant inheritance pattern. This means only one copy of the mutated gene is sufficient to cause the condition. Conversely, mutations in the MEOX1 gene result in autosomal recessive KFS. In autosomal recessive inheritance, both copies of the gene must be mutated for the condition to manifest. Parents of individuals with autosomal recessive KFS each carry one copy of the mutated gene but typically do not show symptoms of the syndrome. When KFS is part of a larger syndrome, its inheritance pattern follows that of the underlying syndrome.