Phenotype characterization and natural history of spondylothoracic dysplasia syndrome: A series of 27 new cases

Abstract

Spondylothoracic dysplasia (STD, MIM#277300) is an autosomal recessive disorder with high prevalence in the Puerto Rican population. It is generally regarded as a lethal condition. Since Jarcho and Levin described it in 1938, it has been referred to as spondylocostal dysplasia, costovertebral dysplasia, Jarcho-Levin syndrome and STD. We have prospectively characterized 27 patients with STD by detailed physical examination, pedigree analysis, thoracic CT scans, and pulmonary function tests (PFTs). Diagnoses were established using spinal radiographs and 3-D reconstructive CT scans to demonstrate fusion of the ribs at the costo-vertebral junction with a fan-like (crab-like) configuration of the thorax. Vertebral segmentation and formation defects were seen throughout the spine with a decrease in the number of vertebral bodies. Characteristic vertebral shape consisted of a decrease in antero-posterior diameter and an increase in lateral length, giving the vertebra a sickle shape. Eight out of 18 prospectively follow patients died within the first 6 months of life, a 44% mortality rate. Cause of death was respiratory insufficiency secondary to pneumonia and pulmonary restriction. This is an important finding since the vast majority of STD syndrome patients cited in the medical literature have died in the newborn and early childhood periods. Age of the remaining patients ranged from 4 months to 47 years. This represents the largest collection of patients with STD reported and it has allowed us to determine a detailed phenotype. Given 56% survival at 6 months, we show that STD is not a lethal syndrome.

Abnormal vertebral segmentation and the notch signaling pathway in man

“…Fusion of the ribs is present posteriorly at their vertebral origin, but otherwise they are usually neatly aligned and packed tightly together. This condition has been well characterized in a recent study (Cornier et al, 2004). Infant mortality is approximately 50% due to restrictive respiratory insufficiency, although the availability of pediatric intensive care greatly improves the prognosis.…”

“…1) neatly describes the appearance. In addition, in horizontal section on CT scanning, the vertebral bodies conform to a "sickle cell" shape (Cornier et al, 2004). Studies of the ultrastructure at necropsy are scarce.…”

Syndromes and Diseases Associated with the Notch Signalling Pathway

“…This is sometimes referred to as the 'tramline' sign. STD has been well delineated from a clinical point of view (Cornier et al, 2004). Most reported cases are Puerto Rican but, although rare, it has been seen globally.…”

Segmentation anomalies of the vertebras and ribs: One expression of the primary developmental field

“…But this nomenclature has become very confusing because of the inconsistent way in which these terms have been used. Moreover, some authors, as Cornier et al [2004], postulate that it is not clear whether the intrinsic pathology of these anomalies is related to the embryonic sclerotomes that form bone tissue (dysplasia) or to the mesoderm itself, in which case the term ''dysostosis'' would be more appropriate. In recent years, a large body of knowledge has emerged from evolutionary developmental biology, epidemiology, and animal and human molecular genetics that may help to identify the different entities and, consequently, should not be ignored in clinical studies [Opitz and Gilbert, 1982;Davidson, 1991;Opitz, 1993Opitz, , 2002Wallin et al, 1993;, 1998aMartínez-Frías, 1994a, 1995, 1996aDavidson et al, 1995;Gilbert et al, 1996;Wei and Sulik, 1996;Dunwoodie et al, 1997;Tribioli and Lufkin, 1999;Turnpenny et al, 1999Turnpenny et al, , 2003Brand-Saberi and Christ, 2000;Bulman et al, 2000;Bannykh et al, 2003;Wellik and Capecchi, 2003].…”