AR = autosomal recessive; SCDO = spondylocostal dysostosis

Genes are listed in alphabetic order.

See Table A. Genes and Databases for chromosome locus and protein.

The percentages in column two are estimates based on published reports [Authors, personal communication].

See Molecular Genetics for information on variants detected in these genes.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Bulman et al [2000], Bonafé et al [2003], Turnpenny et al [2003]

One individual with a deletion of exons 2-4 (detected by an in-house-designed MLPA kit) and one individual with a whole-gene deletion (detected by array CGH and confirmed by in-house-designed MLPA) [Authors, personal communication]

Three reported families and an additional four unreported individuals [P Turnpenny, personal communication]

No deletions or duplications involving HES7, LFNG, MESP2, or RIPPLY2 have been identified in individuals with autosomal recessive SCDO [Authors, personal communication].

Three known families with MESP2-related SCDO [Whittock et al 2004b; Authors, unpublished data]

Six families with TBX6-related SCDO have been reported [Lefebvre et al 2017; P Turnpenny, personal communication].

Large TBX6 deletions/duplications have not been reported in individuals with autosomal recessive SCDO. Heterozygous TBX6 deletions, sometimes in trans with a hypomorphic allele, have been reported in individuals with congenital scoliosis and müllerian aplasia or renal malformations (see Genetically Related Disorders) [Sandbacka et al 2013, Wu et al 2015, Li et al 2022].

One individual with an SCDO-like phenotype including multiple regional segmentation defects of the vertebrae and multiple intervertebral fusions of laminae, in addition to dysmorphic features and cleft palate, was homozygous for a DMRT2 start-loss variant [Bouman et al 2018]. With severe left-sided rib cage deficiency, the infant died at age nine days; to date, it is not known whether DMRT2-related SCDO is a distinct entity.