Klippel-Feil syndrome associated with situs inversus: description of a new case and exclusion of GDF1, GDF3 and GDF6 as causal genes.

Objective: Klippel-Feil syndrome is characterized by faulty segmentation of two or more cervical vertebrae and, in its most severe form, consists of massive cervical vertebral fusion, short neck, low posterior hairline, and limitation of head movement. Several cases associating Klippel-Feil syndrome with situs inversus totalis have been reported. In the present study, we describe the clinical features of a novel case of Klippel-Feil syndrome associated with situs inversus totalis and searched for mutations in GDF1, GDF3 and GDF6 genes, which were recently implicated in the development of skeletal and visceral anomalies.

Methods: A case of Klippel-Feil syndrome associated with situs inversus totalis underwent a full clinical examination including X-ray of cervical spine and thorax, abdominal ultrasound, and computerized tomography scanning of thorax and abdomen. PCR amplification and automated nucleotide sequencing of coding exons and intron-exon junctions of GDF1, GDF3, and GDF6 genes were performed in genomic DNA.

Results: No molecular alterations were found in GDF1, GDF3 and GDF6 genes in this patient.

Conclusion: An additional patient associating Klippel-Feil syndrome and situs inversus totalis is reported. Mutations in GDF1, GDF3, and GDF6 genes were excluded as the cause of this unusual clinical association.