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Klippel-Feil syndrome 1, autosomal dominant(KFS1)

MedGen UID:
396196
Concept ID:
C1861689
Disease or Syndrome
Synonyms: CERVICAL VERTEBRAL FUSION, AUTOSOMAL DOMINANT; KFS1
 
Gene (location): GDF6 (8q22.1)
 
Monarch Initiative: MONDO:0007306
OMIM®: 118100

Definition

Klippel-Feil syndrome is a bone disorder characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae). The vertebral fusion is present from birth. Three major features result from this vertebral fusion: a short neck, the resulting appearance of a low hairline at the back of the head, and a limited range of motion in the neck. Most affected people have one or two of these characteristic features. Less than half of all individuals with Klippel-Feil syndrome have all three classic features of this condition.

In some cases, Klippel-Feil syndrome occurs as a feature of another disorder or syndrome, such as Wildervanck syndrome or hemifacial microsomia. In these instances, affected individuals have the signs and symptoms of both Klippel-Feil syndrome and the additional disorder.

In people with Klippel-Feil syndrome, the fused vertebrae can limit the range of movement of the neck and back as well as lead to chronic headaches and muscle pain in the neck and back that range in severity. People with minimal bone involvement often have fewer problems compared to individuals with several vertebrae affected. The shortened neck can cause a slight difference in the size and shape of the right and left sides of the face (facial asymmetry). Trauma to the spine, such as a fall or car accident, can aggravate problems in the fused area. Fusion of the vertebrae can lead to nerve damage in the head, neck, or back. Over time, individuals with Klippel-Feil syndrome can develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Rarely, spinal nerve abnormalities may cause abnormal sensations or involuntary movements in people with Klippel-Feil syndrome. Affected individuals may develop a painful joint disorder called osteoarthritis around the areas of fused bone or experience painful involuntary tensing of the neck muscles (cervical dystonia). In addition to the fused cervical bones, people with this condition may have abnormalities in other vertebrae. Many people with Klippel-Feil syndrome have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; fusion of additional vertebrae below the neck may also occur.

People with Klippel-Feil syndrome may have a wide variety of other features in addition to their spine abnormalities. Some people with this condition have hearing difficulties, eye abnormalities, an opening in the roof of the mouth (cleft palate), genitourinary problems such as abnormal kidneys or reproductive organs, heart abnormalities, or lung defects that can cause breathing problems. Affected individuals may have other skeletal defects including arms or legs of unequal length (limb length discrepancy), which can result in misalignment of the hips or knees. Additionally, the shoulder blades may be underdeveloped so that they sit abnormally high on the back, a condition called Sprengel deformity. Rarely, structural brain abnormalities or a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect) can occur in people with Klippel-Feil syndrome. [from MedlinePlus Genetics]

Clinical features

From HPO
Abnormality of the kidney
MedGen UID:
78593
Concept ID:
C0266292
Congenital Abnormality
An abnormality of the kidney.
Unilateral renal agenesis
MedGen UID:
75607
Concept ID:
C0266294
Congenital Abnormality
A unilateral form of agenesis of the kidney.
Abnormal limb bone morphology
MedGen UID:
904271
Concept ID:
C4082761
Anatomical Abnormality
Any abnormality of bones of the arms or legs.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Anatomical Abnormality
Any structural anomaly of the heart and blood vessels.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Mixed hearing impairment
MedGen UID:
102336
Concept ID:
C0155552
Disease or Syndrome
A type of hearing loss resulting from a combination of conductive hearing impairment and sensorineural hearing impairment.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Bimanual synkinesia
MedGen UID:
473166
Concept ID:
C0454455
Disease or Syndrome
Involuntary movements of one hand that accompany and mirror intentional movements of the opposite hand.
Abnormality of the nervous system
MedGen UID:
105425
Concept ID:
C0497552
Congenital Abnormality
An abnormality of the nervous system.
Posterior fossa cyst
MedGen UID:
341753
Concept ID:
C1857353
Finding
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
Cervicomedullary schisis
MedGen UID:
868119
Concept ID:
C4022510
Anatomical Abnormality
Fissure within the spinal cord of the neck.
Klippel-Feil syndrome
MedGen UID:
9645
Concept ID:
C0022738
Disease or Syndrome
Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). Genetic Heterogeneity of Klippel-Feil Syndrome Additional forms of KFS include autosomal recessive KFS2 (214300), caused by mutation in the MEOX1 gene (600147) on chromosome 17q21, autosomal dominant KFS3 (613702), caused by mutation in the GDF3 gene (606522) on chromosome 12p13, and autosomal recessive KFS4 (616549), caused by mutation in the MYO18B gene (607295) on chromosome 22q12. See also MURCS association (601076), in which Klippel-Feil anomaly is associated with urogenital anomalies.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Congenital elevation of scapula
MedGen UID:
56291
Concept ID:
C0152438
Congenital Abnormality
A congenital skeletal deformity characterized by the elevation of one scapula (thus, one scapula is located superior to the other).
Abnormal rib morphology
MedGen UID:
330763
Concept ID:
C1842083
Anatomical Abnormality
An anomaly of the rib.
Abnormal vertebral segmentation and fusion
MedGen UID:
870713
Concept ID:
C4025167
Anatomical Abnormality
Congenital muscular torticollis
MedGen UID:
86902
Concept ID:
C0079352
Congenital Abnormality
A congenital form of torticollis resulting from shortening of the sternocleidomastoid muscle and leading to a limited range of motion in both rotation and lateral bending.
Webbed neck
MedGen UID:
113154
Concept ID:
C0221217
Congenital Abnormality
Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Low posterior hairline
MedGen UID:
383755
Concept ID:
C1855728
Finding
Hair on the neck extends more inferiorly than usual.
Limited neck range of motion
MedGen UID:
395202
Concept ID:
C1859212
Finding
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Recent clinical studies

Diagnosis

Da Broi M, Nouri A, Patet G, Paun L, Bartoli A, Molliqaj G, Schaller K, Tessitore E
J Med Case Rep 2023 Dec 23;17(1):528. doi: 10.1186/s13256-023-04263-8. PMID: 38135884Free PMC Article
Giampietro PF, Armstrong L, Stoddard A, Blank RD, Livingston J, Raggio CL, Rasmussen K, Pickart M, Lorier R, Turner A, Sund S, Sobrera N, Neptune E, Sweetser D, Santiago-Cornier A, Broeckel U
Am J Med Genet A 2015 Jan;167A(1):95-102. Epub 2014 Oct 27 doi: 10.1002/ajmg.a.36799. PMID: 25348728

Clinical prediction guides

Pfeiffer RA, Rott HD, Angerstein W
Genet Couns 1990;1(2):133-40. PMID: 2080998