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 ... 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). Clarke et al. (1998) proposed a classification system for KFS in which an autosomal recessive form is characterized by the most rostral fusion at C1 and the presence of severe associated anomalies, including short neck, cardiac defects, and craniofacial anomalies. For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Lubs et al. (1963) reported a family in which 2 of 11 sibs had fusion of vertebrae C5-6; a third sib had narrowing of the interspace. The parents were probably consanguineous.
Juberg and Gershanik (1976) reported ... Lubs et al. (1963) reported a family in which 2 of 11 sibs had fusion of vertebrae C5-6; a third sib had narrowing of the interspace. The parents were probably consanguineous. Juberg and Gershanik (1976) reported a patient with KFS born of consanguineous parents. She had short neck, restricted cervical movement, and low posterior hairline. Radiographic examination showed C1 anomalies and fusion of C2-3 and C3-4. She also had hearing loss. Chemke et al. (1980) described absent ulna and ulnar ray bilaterally in a female infant with KFS. The parents, Iraqi Jews, were not known to be consanguineous. Congenital absence of the ulna is rare; it may occur with the Cornelia de Lange syndrome (122470). In a large kindred, da-Silva (1982) reported 4 sibships with a total of 7 females and 5 males with Klippel-Feil syndrome. Each had unaffected, first-cousin parents. The degree of vertebral fusion was variable: 6 patients had massive fusion of several cervical vertebrae and 2 had cervical, upper thoracic, and lumbar fusions. Fragoso et al. (1982) described an 8-year-old girl who, in addition to KFS, had frontonasal dysplasia, Sprengel deformity (184400), widely spaced nipples, and postaxial polydactyly of the left foot. Facial features included flat facies, low anterior and posterior hairlines, hypertelorism, high-arched palate, and low-set ears. She had a short neck with limited movements. Clarke et al. (1998) reported a family in which the proband displayed the classic KFS triad of vertebral fusion, very short neck, and low hairline associated with fusion of C1-4 and C5-7. Fusion of spinous processes C1-4 was present at birth and did not progress in the following year to include the vertebral bodies. Other features included cleft palate, large pointed ears, and cardiac ventriculoseptal defect. The maternal grandmother had cleft lip and palate without vertebral fusion and a maternal uncle was reported to have had a very short neck. The authors suggested autosomal recessive inheritance with variable expression. Erol et al. (2004) reported a 7-year-old girl of Turkish origin with Klippel-Feil syndrome and Poland anomaly (173800). She had the typical triad of KFS, including very short neck, low occipital hairline, and reduced bilateral neck movements. Radiographic examination showed fusion of C1 and C2 vertebrae. She also had absence of the right pectoralis muscle, hypoplastic right breast, hypoplastic costochondral junctions, and hypoplastic sternum consistent with Poland anomaly. She had no cardiac, vascular, or renal anomalies. Erol et al. (2004) noted that a child with features of KFS, Poland anomaly, and Moebius syndrome (157900) had been reported by Issaivanan et al. (2002), who postulated a disruption in the subclavian artery supply.
In a large consanguineous Saudi family segregating autosomal recessive Klippel-Feil syndrome mapping to chromosome 17q21.31, Mohamed et al. (2013) analyzed the candidate gene MEOX1 and identified a homozygous 1-bp deletion (600147.0001) that segregated fully with the disease and ... In a large consanguineous Saudi family segregating autosomal recessive Klippel-Feil syndrome mapping to chromosome 17q21.31, Mohamed et al. (2013) analyzed the candidate gene MEOX1 and identified a homozygous 1-bp deletion (600147.0001) that segregated fully with the disease and was not found in 210 Saudi controls. Sequencing of the MEOX1 gene in affected sibs from an unrelated consanguineous family revealed homozygosity for a nonsense mutation (600147.0002).