ORPHA: 2311; DO: 0112362;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q26.1 | Spondylocostal dysostosis 2, autosomal recessive | 608681 | Autosomal recessive | 3 | MESP2 | 605195 |
A number sign (#) is used with this entry because autosomal recessive spondylocostal dysostosis-2 (SCDO2) is caused by homozygous or compound heterozygous mutation in the MESP2 gene (605195) on chromosome 15q26.
Spondylocostal dysostosis is a term given to a heterogeneous group of disorders characterized by abnormal vertebral segmentation. For a general phenotypic description and a discussion of genetic heterogeneity of the disorder, see SCDO1 (277300).
Whittock et al. (2004) studied a consanguineous Lebanese Arab family in which 2 offspring were affected with spondylocostal dysostosis. Affected individuals presented with truncal shortening and short necks but no other abnormalities. On radiologic examination, thoracic vertebrae bore a resemblance to those seen in spondylocostal dysostosis due to mutated DLL3, but the lumbar vertebrae appeared more angular and irregular. The vertebral morphology, with regional differences throughout the spine, was well demonstrated by magnetic resonance imaging.
Cornier et al. (2004) described a detailed phenotype for SCDO based on a series of 27 Puerto Rican patients. Eight of 18 prospectively followed patients (44%) died within 6 months from respiratory failure due to pneumonia and pulmonary restriction; the ages of the remaining patients ranged from 4 months to 47 years. Cornier et al. (2004) noted that beyond the 6-month period, all of their patients survived with minimal medical complications and that they had normal intelligence and a good independent quality of life.
The transmission pattern of SCDO2 in the family reported by Whittock et al. (2004) was consistent with autosomal recessive inheritance.
Whittock et al. (2004) demonstrated homozygosity for a 4-bp duplication mutation in the MESP2 gene (605195.0001) in affected members of a consanguineous Lebanese Arab family with spondylocostal dysostosis.
In 11 Puerto Rican probands with spondylocostal dysostosis, Cornier et al. (2008) identified 3 different biallelic mutations in the MESP2 gene (605195.0002-605195.0004). Ten of the probands had been reported by Cornier et al. (2004). The most common allele was E103X (605195.0002), consistent with a founder effect in this population.
Cornier et al. (2004, 2008) noted that the prevalence of spondylocostal dysostosis is very high in Puerto Rico, comprising 49% of the cases reported in the literature. In the study by Cornier et al. (2004), 91% of 27 Puerto Rican patients were from small towns in the northwest part of Puerto Rico.
Cornier, A. S., Ramirez, N., Arroyo, S., Acevedo, J., Garcia, L., Carlo, S., Korf, B. Phenotype characterization and natural history of spondylothoracic dysplasia syndrome: a series of 27 new cases. Am. J. Med. Genet. 128A: 120-126, 2004. [PubMed: 15214000] [Full Text: https://doi.org/10.1002/ajmg.a.30011]
Cornier, A. S., Staehling-Hampton, K., Delventhal, K. M., Saga, Y., Caubet, J.-F., Sasaki, N., Ellard, S., Young, E., Ramirez, N., Carlo, S. E., Torres, J., Emans, J. B., Turnpenny, P. D., Pourquie, O. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am. J. Hum. Genet. 82: 1334-1341, 2008. [PubMed: 18485326] [Full Text: https://doi.org/10.1016/j.ajhg.2008.04.014]
Whittock, N. V., Sparrow, D. B., Wouters, M. A., Sillence, D., Ellard, S., Dunwoodie, S. L., Turnpenny, P. D. Mutated MESP2 causes spondylocostal dysostosis in humans. Am. J. Hum. Genet. 74: 1249-1254, 2004. [PubMed: 15122512] [Full Text: https://doi.org/10.1086/421053]