Spondylocostal Dysplasia Research Articles

Spondylocostal dysplasia: a rare cause of respiratory distress in term neonates

Jarcho-Levin syndrome (JLS) also known as spondylocostal dysplasia is a rare congenital dysplastic disorder involving ribs and vertebrae. It as an autosomal recessive form of inheritance however dominant forms have also been reported. Multiple genes have been postulated to be causative, however exact genetic basis is not known. Infants usually present at birth with respiratory distress and have varying degree of thoracic and vertebral anomalies. We present a case of term male infant with a clinical diagnosis of JLS. The infant presented at birth with distress with no significant antenatal risk factors. On examination he was found to have a short neck, short trunk, accessory nipple with asymmetrical chest wall. X-ray suggested absent ribs (2-8) on left side with hemivertebrae (T3-T8). The baby was managed conservatively and is being followed up with neonatologists, orthopaedicians and pediatric surgeons.

Sleep‐disordered breathing and its management in children with rare skeletal dysplasias

Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia.

Spondylocostal Dysplasia in a 7-Year-Old Sri Lankan Girl Causing Restrictive Lung Disease: A Case Report and Review of the Literature

Spondylocostal dysplasia (SCD) is a rare costovertebral malformation characterised by short-trunk short stature. It is a recessively inherited disorder, and commonly identified disease-causing mutations are in DLL3 gene. The reported prevalence is 1 : 200,000 worldwide, and none was reported from Sri Lanka. We report a 7-year-old Sri Lankan girl with spondylocostal dysplasia presenting with short stature and scoliosis. Disproportionate short stature was noted with short upper segment and small thoracic cavity. Skeletal survey revealed fused vertebra involving T5-T6, T9-T10, and L3-L4. Butterfly vertebrae were noted in T2, T4, T6, and T9. Diagnosis of SCD was made based on classic radiological features including vertebral fusion and rib abnormalities. Spirometry was performed due to small thoracic cavity which showed results compatible with moderate to severe restrictive lung disease. The child did not report respiratory difficulties or recurrent chest infections up to the presentation. She was referred to an orthopaedic team which recommended conservative management with close follow-up. In conclusion, spondylocostal dysplasia should be considered in short-trunk short stature with rib abnormalities in the absence of limb shortening. Appropriate treatment and follow-up for restrictive lung disease would determine the long-term outcome.

Jarcho-Levin Syndrome: Two Consecutive Cases in the Same Family

Jarcho-Levin Syndrome was first defined in 1938 by Saul Jarcho and Paul Levin. In the medical literature Jarcho-Levin Syndrome has a variety of synonyms such as Spondylocostal dysplasia/Dysostosis, Spondylocostal Dysostosis (SCD), Spondylothoracic dysplasia/Dysostosis and costovertebral dysplasia. For years the SCD and a similar disorder, spondylothoracic dysplasia, were considered the same disorder and referred as Jarcho-Levin Syndrome. Today we know that these two disorders are different clinical entities with different causes and that the term Jarcho-Levin Syndrome should be reserved for individuals with Spondylocostal dysplasia. Affected individuals with SCD have various abnormalities in the development of the spine and ribs. Due to these abnormalities they are more prone to develop thoracic insufficiency syndrome which may eventually lead to early neonatal death. In the current case report we describe two consecutive cases with SCD in the same family. In the case of a strong clinical suspicion from the findings of the ultrasound scan we should proceed to a molecular genetic diagnosis of a mutation in DLL3, MESP2, LFNG and HES7 gene by sequencing the entire coding area of the fetal Deoxyribonucleic acid (DNA).

Prenatally Diagnosed and Surviving Patient with Jarcho-Levin Syndrome: Case Report with Literature Review

Jarcho-Levin syndrome is a congenital disorder characterized by several vertebral and costal anomalies. Other abnormalities have also been described, including neural tube defects, Arnold-Chiari malformation, renal/urinary tract abnormalities, hydrocephalus, hydroureteronephrosis, and meningomyelocele. We describe a spondylocostal dysplasia form of Jarcho-Levin syndrome that was prenatally diagnosed at 11 weeks of gestation and surviving. Although the patient had sporadic-type Jarcho- Levin syndrome, with normal karyotype and no family history of disease, the assessment of inheritance patterns and genetic counseling for the parents was important to inform them about the potential risks.

Growing spinal systems and early onset deformities: is hyperkhyphosis a contraindication?

Materials and methods We retrospectively reviewed 16 paediatric patients affected by kyphotic spinal deformity (T3-T12 kyphosys > 60°) surgically treated with Growing Rod or VEPTR-like systems from 2006 to 2011. There were 8 males and 8 females, with a mean age of 7 years (range, 4 to 11). The aetiology was: idiopathic scoliosis (5 cases), kyphosis in Morquio disease (1) and in Pott disease (1), congenital scoliosis (3), trisomy 8 (1), Escobar syndrome (1), Prader Willi (1), spondylocostal dysplasia (1), arthrogryposis (2). Dual growing rod was implanted in 9 cases, VEPTR in 9 (always rib to spine construct). Pre-operative main thoracic scoliosis averaged 64° (range, 10° to 100°), lumbar scoliosis 55° and thoracic kyphosis 71° (60° to 90°), 67° in patients treated with growing rod and 77° for those treated with VEPTR.

Jarcho-Levin syndrome with diastematomyelia : A case report and review of literature

Jarcho–Levin syndrome (JLS) is a type of segmental costovertebral malformation. It is a congenital disorder characterized by a variety of vertebral and costal anomalies. Only four cases of Jarcho–Levin syndrome with diastematomyelia have been reported in the literature. We report the fifth case of Jarcho–Levin syndrome with diastematomyelia and review the literature. A one-and-half-year-old male child born of full-term normal delivery was brought with complaints of progressively increasing weakness in lower limbs with inability to stand since 1 month. Radiological examination revealed irregular fusion of ribs, spina bifida, and diastematomyelia at L2–L3 vertebral level. The patient underwent L1 to L3 laminectomy. A large bony spur was identified and excised with microrongeurs. Spondylocostal dysplasia may be associated with diastematomyelia or other surgically correctable occult intraspinal anomalies which may be diagnosed in early asymptomatic stage by magnetic resonance image screening of spine.

Vertical Expandable Prosthetic Titanium Rib as Treatment of Thoracic Insufficiency Syndrome in Spondylocostal Dysplasia

Spondylocostal dysplasia (SCD) constitutes a heterogeneous patient group with multiple vertebral formations and segmentation defects of the entire spine, with asymmetric rib malformations. Respiratory failure has been reported in spondylocostal dysplasia secondary to thoracic insufficiency syndrome. The vertical expandable prosthetic titanium rib (VEPTR) reconstructs the chest wall to address the thoracic insufficiency seen in this patient population. The purpose of this study is to evaluate spinal deformity correction and respiratory function outcomes in a spondylocostal dysplasia population treated with VEPTR. A cohort of 20 patients with spondylocostal dysplasia and 2-year follow-up were evaluated from a multicenter IDE study of 214 patients who had surgery with the VEPTR device. Data collected included gender, nonskeletal malformations, age at surgery, number of procedures, estimated blood loss, length of stay, and surgical time. Clinical and radiographic parameters were collected, and respiratory function was assessed. In 14 of 20 patients (70%), spinal deformity was controlled evidenced by a decrease of the initial Cobb coronal angle at last follow-up. Fourteen patients (70%) maintained their oxygen level throughout treatment. At preoperative and last evaluation, assisted ventilation rating (AVR) scores showed that 5 patients improved their level of ventilation and 14 patients maintained their AVR level at room air. One patient decreased his level from supplemental oxygen to night ventilation. Mean thoracic spinal length (growth) by year was 0.82 cm. No mortality occurred in this group of patients. VEPTR implantation in SCD allows continued thoracic spine growth while controlling progressive spine deformity. The improved AVR ratings after surgery suggest a beneficial effect on the natural history of TIS in this population. Mortality and complication rate seem acceptable in this high-risk population of SCD patients. Therapeutic study, Level IV, (case series, no comparison group).

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to FLNB mutations

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to <i>FLNB</i> mutations

Rokitanskys Erstbeschreibung einer spondylokostalen Dysplasie

The bicentenary of Carl Rokitansky's birth prompted us to evaluate his less well-known work related to osteopathology. Of various articles containing humoropathological interpretations of osseous diseases, one work should be highlighted. It is, to the best of our knowledge, the first description of a spondylocostal dysplasia, re-discovered many years later, precisely described and accompanied by an excellent illustration.

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

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.

Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm.

A loss-of-function mutation in the mouse delta-like3 (Dll3) gene has been generated following gene targeting, and results in severe axial skeletal defects. These defects, which consist of highly disorganised vertebrae and costal defects, are similar to those associated with the Dll3-dependent pudgy mutant in mouse and with spondylocostal dysplasia (MIM 277300) in humans. This study demonstrates that Dll3(neo) and Dll3(pu) are functionally equivalent alleles with respect to the skeletal dysplasia, and we suggest that the three human DLL3 mutations associated with spondylocostal dysplasia are also functionally equivalent to the Dll3(neo) null allele. Our phenotypic analysis of Dll3(neo)/Dll3(neo) mutants shows that the developmental origins of the skeletal defects lie in delayed and irregular somite formation, which results in the perturbation of anteroposterior somite polarity. As the expression of Lfng, Hes1, Hes5 and Hey1 is disrupted in the presomitic mesoderm, we suggest that the somitic aberrations are founded in the disruption of the segmentation clock that intrinsically oscillates within presomitic mesoderm.

Diverse requirements for Notch signalling in mammals.

The Notch signalling pathway has a central role in a wide variety of developmental processes and it is not therefore surprising that mutations in components of this pathway can cause dramatic human genetic disorders. One developmental process in which the Notch pathway is involved at multiple levels is somitogenesis, the mechanism by which the embryo is divided into segments that ultimately form structures such as the axial skeleton and skeletal muscle of the trunk. We are investigating the human genetic disorder spondylocostal dysplasia (SCD), which is a group of malsegmentation syndromes that occur when this process is disrupted. Mutations in the Notch ligand DELTA-LIKE 3 (DLL3) are responsible for cases of autosomal recessive SCD type I (SCDO1), and we are using information derived from these mutations to study the structure of the DLL3 protein. To aid in elucidation of the underlying developmental defect in SCDO1, we have generated a mouse model by targeted deletion of the Dll3 gene (Dunwoodie et al., 2002). These mice show segmentation defects similar to those seen in SCDO1. In addition, these mice have a distinct set of neural defects that may be useful in future neurological assessment of affected individuals. Finally, since not all cases of SCD are due to mutation of DLL3, we are investigating various genes to find other candidates involved in this genetic disease.

Mapping of the autosomal recessive (AR) craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation of genetic heterogeneity for mild AR spondylocostal dysplasia

We report on a four-generation inbred family including 10 individuals affected with a form of craniotubular dysplasia (CTD). All affected patients were born to consanguineous healthy parents; this finding, together with the equal sex ratio among affected individuals and the occurrence of only normal individuals among their offspring, indicates that the disease in this family is an autosomal recessive (AR) trait. Taking into account the segregation pattern of the disease in the family and the radiological characteristics of two young CTD patients, the most likely diagnosis for the defect is AR craniometaphyseal dysplasia (CMD). CMD is a CTD, with both autosomal dominant (AD) and recessive forms. The description of the present genealogy confirms the AR pattern of inheritance of some cases of CMD and contributes to a better delineation of the clinical spectrum of AR CMD, suggesting a more pronounced diaphyseal involvement in the AR compared with the AD CMD. Through genomewide scanning, we mapped the AR CMD to a 7 cM interval, between D6S302 and D6S1639, at 6q21-22 region. We have also excluded the positional candidate COL10A1 gene as being the responsible for this disorder. Curiously, a form of AR spondylocostal dysplasia (SD) also segregates in the family, including one affected individual with both conditions. The gene DLL3, mapped to 19q13 region, was recently found to be responsible for one form of AR SD; however, we did not find evidence of linkage between this 19q region and the SD segregating in our family, thus implying in genetic heterogeneity for AR SD.

Chromosome 18q22.2-->qter deletion and a congenital anomaly syndrome with multiple vertebral segmentation defects.

Multiple vertebral segmentation defects occur in a group of conditions variably associated with anomalies of other organ systems. This report describes a female child in whom a deletion of chromosome...

Spondylocostal dysplasia and neural tube defects.

Spondylocostal dysplasia (Jarcho-Levin syndrome) comprises multiple malformations of the vertebrae and ribs coupled with a characteristic clinical picture of short neck, scoliosis, short trunk, and deformity of the rib cage. We describe a patient with the syndrome who also had spina bifida and diastematomyelia. We surmise that this association is not coincidental. Additional evidence is needed to support the hypothesis that spondylocostal dysplasia and neural tube defects are aetiologically related.

Sporadic occurrence of spondylocostal dysplasia and mesocardia in a Japanese girl

American Journal of Medical GeneticsVolume 37, Issue 3 p. 427-428 Letter to the Editor Sporadic occurrence of spondylocostal dysplasia and mesocardia in a Japanese girl Takehiko Ohzeki M.D., Corresponding Author Takehiko Ohzeki M.D. Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanDepartment of Pediatrics, Tottori University School of Medicine, Yonago, 683, JapanSearch for more papers by this authorMasahiro Shiraishi, Masahiro Shiraishi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorYoshihiro Matsumoto, Yoshihiro Matsumoto Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorJunji Takagi, Junji Takagi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHiroko Motozumi, Hiroko Motozumi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKeiichi Hanaki, Keiichi Hanaki Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorNobuo Ishitani, Nobuo Ishitani Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHiroko Matsuda-Ohtahara, Hiroko Matsuda-Ohtahara Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHirofumi Okuda, Hirofumi Okuda Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorTadataka Hoshika, Tadataka Hoshika Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorYoshihiro Ogihara, Yoshihiro Ogihara Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKazuo Shiraki, Kazuo Shiraki Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKichizo Yamamoto, Kichizo Yamamoto Department of Orthopedics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this author Takehiko Ohzeki M.D., Corresponding Author Takehiko Ohzeki M.D. Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanDepartment of Pediatrics, Tottori University School of Medicine, Yonago, 683, JapanSearch for more papers by this authorMasahiro Shiraishi, Masahiro Shiraishi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorYoshihiro Matsumoto, Yoshihiro Matsumoto Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorJunji Takagi, Junji Takagi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHiroko Motozumi, Hiroko Motozumi Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKeiichi Hanaki, Keiichi Hanaki Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorNobuo Ishitani, Nobuo Ishitani Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHiroko Matsuda-Ohtahara, Hiroko Matsuda-Ohtahara Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorHirofumi Okuda, Hirofumi Okuda Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorTadataka Hoshika, Tadataka Hoshika Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorYoshihiro Ogihara, Yoshihiro Ogihara Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKazuo Shiraki, Kazuo Shiraki Department of Pediatrics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this authorKichizo Yamamoto, Kichizo Yamamoto Department of Orthopedics, Tottori University School of Medicine, Yonago, JapanSearch for more papers by this author First published: November 1990 https://doi.org/10.1002/ajmg.1320370326Citations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume37, Issue3November 1990Pages 427-428 RelatedInformation

ANTENATAL DIAGNOSIS OF LUNG HYPOPLASIA

Evaluating the fetal lung is a component of the ultrasonic assessment of newborn viability. We have combined subjective ultrasonic visualization of the lung with quantitative parameters including the ratio of cross sectional areas of the heart and thorax, average rib spacing (midaxillary line), relative lung reflectivity, and the occurrence and pattern of diaphragmatic movement. We have been able to recognize pulmonary hypoplasia antenatally in 21 cases, 18 through 35 weeks gestational age (3-renal agenesis, 3-renal dysgenesis, prune belly S., 3 nonimmune and 1 immune hydrops, 2-prolonged ROM, triploidy, trisomy 13, chromototrophic dwarves). We have also seen lesser degrees of hypoplasia with spondylocostal dysplasia, massive pulmonary replacement with adenomatoid malformation, 2 sequestrations, and one case of increased lung volume with decreased reflectivity later found to have laryngeal atresia.Lung hypoplasia can be diagnosed antenatally. Detection of severe hypoplasia contraindicates decompressive intra-fetal procedures or operative delivery.

Spondylo-costal dysplasia. A further report--review of 14 cases.

Fourteen patients with spondylo-costal dysplasia were analysed. 3 of them presented without obvious associated anomalies "pure" spondylo-costal dysplasias; 2 had several components consistent with Vater (Vacterl)-Association; 2 showed malformations which are often encountered in Vater (Vacterl)-Association; 4 presented with minor malformations; 3 had major associated malformations rarely seen in Vater (Vacterl)-Association. Thoracic spine and costal malsegmentation can be sporadically observed in other "errors in septation complex" (axial mesodermal dysplasia) including severe myelomeningocoele and diastematomyelia.

Spondylo-costal dysplasia--severe and moderate types (report of 8 cases).

SUMMARYEight cases of spondylo‐costal dysplasia, three of severe and five of moderate types are described. In the author's opinion spondylocostal dysplasia represents a group of genetically different diseases characterised radiologically by malsegmentation of the spine and dysplastic/hypoplastic changes of the ribs.Spondylo‐costal dysplasia is a relatively common finding in severe forms of myelomenuigocoele.