Spondylocostal dysostosis

Last updated
Jarcho-Levin Syndrome
Ajr std2 ap.png
Radiograph depicting typical skeletal features of Jarcho-Levin syndrome, subtype spondylothoracic dysplasia. Note fanlike configuration of the ribs, with extensive posterior fusion, along with multiple vertebral segmentation defects.
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

Spondylocostal dysostosis, also known as Jarcho-Levin syndrome (JLS), is a rare, heritable axial skeleton growth disorder. It is characterized by widespread and sometimes severe malformations of the vertebral column and ribs, shortened thorax, and moderate to severe scoliosis and kyphosis. Individuals with Jarcho-Levin typically appear to have a short trunk and neck, with arms appearing relatively long in comparison, and a slightly protuberant abdomen. Severely affected individuals may have life-threatening pulmonary complications due to deformities of the thorax. The syndrome was first described by Saul Jarcho and Paul M. Levin at Johns Hopkins University in 1938. [1]

Contents

Genetics

Types include:

Type OMIM GeneLocus
SCDO1 277300 DLL3 19q13
SCDO2 608681 MESP2 15q26.1
SCDO3 609813 LFNG 7p22
SCDO4 122600 GDF6 8q22.1

Diagnosis

Subtypes and characteristics

In 1968, Dr. David Rimoin and colleagues in Baltimore first distinguished between the two major presentations of Jarcho-Levin. [2] Both conditions were characterized as failures of proper vertebral segmentation. However, the condition within the family described in their article appeared to be inherited in an autosomal dominant fashion and had a less severe course than that reported by other investigators. They specified their condition as spondylocostal dysplasia, which has since become known as spondylocostal dysostosis. The subtype of Jarcho-Levin with which they contrasted their reported cases to is now known as spondylothoracic dysplasia.

Spondylothoracic dysplasia

Spondylothoracic dysplasia, or STD, has been repeatedly described as an autosomal recessively inherited condition that results in a characteristic fan-like configuration of the ribs with minimal intrinsic rib anomalies. Infants born with this condition typically died early in life due to recurrent respiratory infections and pneumonia due to their restricted thorax. [3] [4] [5] Recently, a report [6] has documented that actual mortality associated with STD is only about 50%, with many survivors leading healthy, independent lives.

Spondylocostal dysostosis

Characteristic radiograph from child with Jarcho-Levin syndrome, spondylocostal dysostosis subtype Ajmg scd ap.jpg
Characteristic radiograph from child with Jarcho-Levin syndrome, spondylocostal dysostosis subtype

In contrast to STD, the subtype spondylocostal dysostosis, or SCD features intrinsic rib anomalies, in addition to vertebral anomalies. Intrinsic rib anomalies include defects such as bifurcation, broadening and fusion that are not directly related to the vertebral anomalies (such as in STD, where extensive posterior rib fusion occurs due to segmentation defects and extreme shortening of the thoracic vertebral column). [6] In both subtypes, the pulmonary restriction may result in pulmonary hypertension, and have other potential cardiac implications. [7]

Management

Prognosis

Babies born with Jarcho-Levin may be very healthy and grow up to lead normal lives. [6] However, many individuals with Jarcho-Levin suffer from problems of respiratory insufficiency secondary to volume-restricted thoraces. These individuals will often develop pulmonary complications and die in infancy or early childhood. [1] [8] [9] [10] [11] The disparity in outcomes of those with the syndrome is related to the fact that Jarcho-Levin actually encompasses two or more distinct syndromes, each with its own range of prognoses. The syndromes currently recognized as subtypes of Jarcho-Levin are termed spondylothoracic dysplasia and spondylocostal dysostosis. The disease is related to the SRRT gene. [12]

Epidemiology

As of 2017 about 20 cases of Spondylocostal dysostosis have been reported in literature. [13]

Sr. No.Name of Author/sYearNumber of cases reportedBrief description
1Elier JL and Morton JM19701Diastematomyelia occurred in association Jarcho–Levin syndrome in an infant born to a woman who abused lysergic acid diethylamide during pregnancy
2Reyes et al.19891Diastematomyelia (type I split cord malformation) as a component of Jarcho–Levin syndrome
3Giacoia GP et al.19911Jarcho–Levin syndrome associated with spina bifida and diastematomyelia (type I split cord malformation)
4Duru S et al.19992First case of 2-year-old girl, spondylocostal dysostosis with lipomyelomeningocele, and polythelia on the right side. Second case of 6-month-old girl, spondylocostal dysostosis with myelomeningocele and hydrocephalus
5Etus et al.20031Case report of Jarcho–Levin syndrome with diastematomyelia (type I split cord malformation) in a 7-year-old girl
6Nadkarni, TD et al.200522 patients with segmental costovertebral malformation, a form of spondylocostal dysostosis, associated with tethering of the conus to a lipomyelomeningocoele.
7Vázquez-López, ME et al.20051Preterm-newborn girl, irregular ribs, Misalignment of vertebral bodies with hemivertebrae at dorsal level.
8Yi S et al.20061Spondylocostal dysostosis with intrathoracic myelomeningocele
9Rosa RFM et al.20093Patient 1: white girl, 22 months old, born with a lumbar meningomyelocele. Patient 2: white girl, 22 months old, spina bifida occulta at L5/S1. Patient 3: white girl, nine days old, with thoracolombar meningocele.
10Sparrow DB et al.20081Caucasian Mediterranean child with hydrocephalus and myelomeningocele, shortened thorax, ectopic and stenotic anus, and talipes associated with SCDO-4
11Çetinkaya M et al.20081Male child born at 40 weeks of gestation with lumbosacral myelomeningocele.
12Kansal R et al.20111One and half year old male child of Jarcho–Levin syndrome with spina bifida and diastematomyelia (type I split cord malformation)
13Dizostozis ES et al.201312-year-old female, with double nipples on the right side and type I split cord malformation and tethered cord
14Anjankar SD et al.201418-month-old male child with lipomyelomeningocele with rib cage defect on left side
15Rafid Alaskary201725 days old neonate with hydrocephalus and spina bifida with absence of 7 ribs in the left side of the chest wall with vertebral deformity and scoliosis. Second case 20 days old female with [14] myelomeningocele, hydrocephalus, absence ribs, vertebral deformity.

Terminology

"Type 1" is also known as "Jarcho-Levin syndrome", or "JLS".

While clinicians almost unanimously refer to the syndrome as "Jarcho-Levin", reports have variously labelled or referred to the condition as all of the following: Hereditary malformations of the vertebral bodies, [1] hereditary multiple hemivertebrae, [8] syndrome of bizarre vertebral anomalies, [3] spondylocostal dysplasia, [2] spondylothoracic dysplasia, [4] costovertebral anomalies, [15] costovertebral dysplasia, [16] spondylothoracic dysplasia, [17] occipito-facial-cervico-thoracic-abdomino-digital dysplasia [18] (deemed "ridiculously long" and "unwarranted" by OMIM), [19] and spondylocostal dysostosis. [20]

A closely related condition termed "Costovertebral segmentation defect with mesomelia and peculiar facies", or Covesdem syndrome, was first described in 1978 in India. [21]

Related Research Articles

Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. Oligohydramnios is the decrease in amniotic fluid volume sufficient to cause deformations in morphogenesis of the baby.

<span class="mw-page-title-main">Ellis–Van Creveld syndrome</span> Medical condition

Ellis–Van Creveld syndrome is a rare genetic disorder of the skeletal dysplasia type.

<span class="mw-page-title-main">Alagille syndrome</span> Medical condition

Alagille syndrome (ALGS) is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 30,000 to 1 in every 40,000 live births. It is named after the French pediatrician Daniel Alagille, who first described the condition in 1969.

<span class="mw-page-title-main">Klippel–Feil syndrome</span> Congenital condition characterised by fusion of two or more vertebrae in the neck

Klippel–Feil syndrome (KFS), also known as cervical vertebral fusion syndrome, is a rare congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck. It results in a limited ability to move the neck and shortness of the neck, resulting in the appearance of a low hairline.

<span class="mw-page-title-main">Microtia</span> Medical condition

Microtia is a congenital deformity where the auricle is underdeveloped. A completely undeveloped pinna is referred to as anotia. Because microtia and anotia have the same origin, it can be referred to as microtia-anotia. Microtia can be unilateral or bilateral. Microtia occurs in 1 out of about 8,000–10,000 births. In unilateral microtia, the right ear is most commonly affected. It may occur as a complication of taking Accutane (isotretinoin) during pregnancy.

<span class="mw-page-title-main">Popliteal pterygium syndrome</span> Medical condition

Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the popliteal web syndrome and, more inclusively, the facio-genito-popliteal syndrome. The term PPS was coined by Gorlin et al. in 1968 on the basis of the most unusual anomaly, the popliteal pterygium.

Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condition occurs in the womb. Congenital vertebral anomalies include alterations of the shape and number of vertebrae.

<span class="mw-page-title-main">Robinow syndrome</span> Rare genetic disorder characterized by a fetal face

Robinow syndrome is an extremely rare genetic disorder characterized by short-limbed dwarfism, abnormalities in the head, face, and external genitalia, as well as vertebral segmentation. The disorder was first described in 1969 by human geneticist Meinhard Robinow, along with physicians Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.

<span class="mw-page-title-main">Majewski's polydactyly syndrome</span> Medical condition

Majewski's polydactyly syndrome, also known as polydactyly with neonatal chondrodystrophy type I, short rib-polydactyly syndrome type II, and shorts rib-polydactyly syndrome, is a lethal form of neonatal dwarfism characterized by osteochondrodysplasia with a narrow thorax, polysyndactyly, disproportionately short tibiae, thorax dysplasia, hypoplastic lungs and respiratory insufficiency. Associated anomalies include protruding abdomen, brachydactyly, peculiar faces, hypoplastic epiglottis, cardiovascular defects, renal cysts, and also genital anomalies. Death occurs before or at birth.

<span class="mw-page-title-main">DLL3</span> Protein-coding gene in the species Homo sapiens

Delta-like 3 (Drosophila), also known as DLL3, is a protein which in humans is encoded by the DLL3 gene. Two transcript variants encoding distinct isoforms have been identified for this gene.

<span class="mw-page-title-main">Oculodentodigital dysplasia</span> Medical condition

Oculodentodigital syndrome is an extremely rare genetic condition that typically results in small eyes, underdeveloped teeth, and syndactyly and malformation of the fourth and fifth fingers. It is considered a kind of ectodermal dysplasia.

<span class="mw-page-title-main">Frontonasal dysplasia</span> Medical condition

Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

<span class="mw-page-title-main">Fibrochondrogenesis</span> Medical condition

Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.

<span class="mw-page-title-main">Miller syndrome</span> Medical condition

Miller syndrome, also known as Genée–Wiedemann syndrome, Wildervanck–Smith syndrome or postaxial acrofacial dysostosis, is an extremely rare genetic condition that manifests as craniofacial, limb and eye deformities. It is caused by a mutation in the DHODH gene. The incidence of the condition is not known, and nothing is known about its pathogenesis.

<span class="mw-page-title-main">Fryns syndrome</span> Medical condition

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period. Fryns (1987) reviewed the syndrome.

<span class="mw-page-title-main">MESP2</span> Protein-coding gene in the species Homo sapiens

Mesoderm posterior protein 2 (MESP2), also known as class C basic helix-loop-helix protein 6 (bHLHc6), is a protein that in humans is encoded by the MESP2 gene.

<span class="mw-page-title-main">HES7 gene</span> Protein-coding gene in humans

(HES7) or bHLHb37 is protein coding mammalian gene found on chromosome 17 in humans. HES7 is a member of the Hairy and Enhancer of Split families of Basic helix-loop-helix proteins. The gene product is a transcription factor and is expressed cyclically in the presomitic mesoderm as part of the Notch signalling pathway. HES7 is involved in the segmentation of somites from the presomitic mesoderm in vertebrates. The HES7 gene is self-regulated by a negative feedback loop in which the gene product can bind to its own promoter. This causes the gene to be expressed in an oscillatory manner. The HES7 protein also represses expression of Lunatic Fringe (LFNG) thereby both directly and indirectly regulating the Notch signalling pathway. Mutations in HES7 can result in deformities of the spine, ribs and heart. Spondylocostal dysostosis is a common disease caused by mutations in the HES7 gene. The inheritance pattern of Spondylocostal dysostosis is autosomal recessive.

<span class="mw-page-title-main">Pascual-Castroviejo syndrome type 1</span> Medical condition

Pascual-Castroviejo syndrome type 1 is a rare autosomal recessive condition characterized by facial dysmorphism, cognitive impairment and skeletal anomalies.

References

  1. 1 2 3 Jarcho, S.; Levin, P.M. (1938). "Hereditary malformation of the vertebral bodies". Bull Johns Hopkins Hosp. 62: 216–226.
  2. 1 2 Rimoin, D.L.; Fletcher, B.D.; McKusick, V.A. (1968). "Spondylocostal dysplasia. A dominantly inherited form of short-trunked dwarfism". Am J Med. 45 (6): 948–953. doi:10.1016/0002-9343(68)90193-9. PMID   5722643.
  3. 1 2 Lavy, N.W.; Palmer, C.G.; Merritt, A.D. (1966). "A syndrome of bizarre vertebral anomalies". J Pediatr. 69 (6): 1121–1125. doi:10.1016/S0022-3476(66)80304-9. PMID   5953839.
  4. 1 2 Moseley, J.E.; Bonforte, R.J. (May 1, 1969). "Spondylothoracic Dysplasia--a Syndrome Of Congenital Anomalies". American Journal of Roentgenology. 106 (1): 166–169. doi:10.2214/ajr.106.1.166. PMID   5769299.
  5. ↑ Pochaczevsky, R.; Ratner, H.; Perles, D.; Kassner, G.; Naysan, P. (1971). "Spondylothoracic dysplasia". Radiology. 98 (1): 53–8. doi:10.1148/98.1.53. PMID   5541431.
  6. 1 2 3 Cornier, A.S.; Ramirez, N.; Arroyo, S.; Acevedo, J.; Garcia, L.; Carlo, S.; Korf, B. (2004). "Phenotype characterization and natural history of spondylothoracic dysplasia syndrome: A series of 27 new cases". American Journal of Medical Genetics. 128 (2): 120–126. doi:10.1002/ajmg.a.30011. PMID   15214000. S2CID   25629794.
  7. ↑ Turnpenny, Peter, D., BSc, MB, ChB, FRCP, FRCPCH, FRCPath, Elizabeth Young, BSc, PhD; ICVS (International Consortium for Vertebral Anomalies and Scoliosis). "Spondylocostal Dysostosis: Autosomal Recessive", WEB, post 8/29/2009, last updated on 1/17/2013. See outside link.
  8. 1 2 Van Der Sar, A. (1952). "Hereditary Multiple Hemivertebrae". Documenta de Medicina Geographica et Tropica.
  9. ↑ Poor, M.A.; Alberti, O.J.R.; Griscom, N.T.; Driscoll, S.G.; Holmes, L.B. (1983). "Nonskeletal malformations in one of three siblings with Jarcho-Levin syndrome of vertebral anomalies". The Journal of Pediatrics. 103 (2): 270–272. doi:10.1016/S0022-3476(83)80365-5. PMID   6875723 . Retrieved 2007-12-15.
  10. ↑ Karnes, P.S.; Day, D.; Berry, S.A.; Pierpont, M.E.M. (1991). "Jarcho-Levin syndrome: four new cases and classification of subtypes". American Journal of Medical Genetics. 40 (3): 264–270. doi:10.1002/ajmg.1320400304. PMID   1951427 . Retrieved 2007-12-15.
  11. ↑ Giacoia, G.P.; Say, B. (1991). "Spondylocostal dysplasia and neural tube defects". Journal of Medical Genetics. 28 (1): 51–3. doi:10.1136/jmg.28.1.51. PMC   1016749 . PMID   1999834 . Retrieved 2007-12-15.
  12. ↑ "SRRT serrate, RNA effector molecule [Homo sapiens (Human)] – Gene – NCBI".
  13. ↑ Anjankar SD, Subodh R (2014). "Spondylocostal dysostosis with lipomyelomeningocele: Case report and review of the literature". J Pediatr Neurosci. 9 (3): 249–52. doi: 10.4103/1817-1745.147580 . PMC   4302546 . PMID   25624929.
  14. ↑ "Yahoo". Yahoo. Retrieved 2019-05-04.
  15. ↑ Norum, R.A.; McKusick, V.A. (1969). "Costovertebral anomalies with apparent recessive inheritance". Birth Defects Original Article Series. 18: 326–329.
  16. ↑ Cantu, J.M.; Urrusti, J.; Rosales, G.; Roms, A. (1944). "Evidence for autosomal recessive inheritance of costovertebral dysplasia". Clinical Genetics. 2 (3): 149–154. doi:10.1111/j.1399-0004.1971.tb00270.x. PMID   5111758. S2CID   42036057.
  17. ↑ Castroviejo, I.P.; Rodriguez-Costa, T.; Castillo, F. (1973). "Spondylo-thoracic dysplasia in three sisters". Dev Med Child Neurol. 15 (3): 348–354. doi:10.1111/j.1469-8749.1973.tb04891.x. PMID   4718686. S2CID   11914535.
  18. ↑ Perez-Comas, A.; Garcia-Castro, J.M. (1974). "Occipito-facial-cervico-thoracic-abdomino-digital dysplasia; Jarcho-Levin syndrome of vertebral anomalies. Report of six cases and review of the literature". J Pediatr. 85 (3): 388–391. doi:10.1016/S0022-3476(74)80126-5. PMID   4372555.
  19. ↑ "OMIM Entry – #277300 – Spondylocostal Dysostosis 1, Autosomal Recessive; SCDO1" . Retrieved 21 January 2019.
  20. ↑ Franceschini, P.; Grassi, E.; Fabris, C.; Bogetti, G.; Randaccio, M. (1974). "The autosomal recessive form of spondylocostal dysostosis". Radiology. 112 (3): 673–675. doi:10.1148/112.3.673. PMID   4843303.
  21. ↑ Wadia, R.S.; Shirole, D.B.; Dikshit, M.S. (1978). "Recessively inherited costovertebral segmentation defect with mesomelia and peculiar facies (Covesdem syndrome): A new genetic entity?". British Medical Journal. 15 (2): 123–127. doi:10.1136/jmg.15.2.123. PMC   1013660 . PMID   641945.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.