Information on the following diseases can be found in the Related Disorders section of this report:

• Thanatophoric Dysplasia

Jarcho-Levin Syndrome is characterized by multiple skeletal deformities caused by fused and/or malformed vertebrae, small, malformed or missing ribs, and a chest cavity that is to small for the infant’s lungs especially as the lungs grow. There is incomplete development (dysplasia) of one side of certain vertebrae (hemivertebrae), fusion of certain ribs, and/or other rib malformations. Consequently the infant is subject to repeated and severe infections of the lungs (pneumonia).

As a result of these developmental problems, the neck, trunk and torso appear to be short so that patients are considered to be of “short stature” or dwarfs. The fingers are usually webbed (syndactyly), elongated and permanently bent (camptodactyly).

In addition, symptoms may include a broad forehead, a wide nasal bridge, nostrils that are tipped forward (anteverted nares), upwardly slanted eyelids, and an enlarged posterior skull. Occasionally distention of the stomach and pelvis may occur due to an obstruction of the bladder. Undescended testicles, absent external genitalia, a double uterus, closed or absent anal and bladder openings, a single umbilical artery, and defects of the brain may also be present.

SCDO2 is milder than SCDO1 in that not all vertebrae are affected.
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There are two forms of Jarcho-Levin syndrome that are transmitted as autosomal recessive genetic traits. SCDO1 is caused by an abnormality in the DLL3 gene located on chromosome 19 at 19q13. SCDO2 is caused by an abnormality in the MESP2 gene located on chromosome 15 at 15q26.1.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 19q13” refers to band 13 on the long arm of chromosome 19. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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Jarcho-Levin Syndrome is a very rare disorder that affects males and females in equal numbers. There seems to be a higher incidence of this disorder in people with Spanish heritage.

Some of the symptoms of the following disorder may be similar to those of Jarcho-Levin Syndrome:

Thanatophoric Dysplasia is a progressive genetic disorder that is characterized by severe growth deficiencies, a large head (hydrocephalus), a low nasal bridge, and small face. There may also be a small thorax with short ribs, short flattened vertebrae, obstruction of the kidney (hydronephrosis), and a closed or absent anus (atresia).

Diagnosis
Jarcho-Levin syndrome is diagnosed by the presence of abnormalities in the spine, back and chest that are present at birth. Diagnosis can sometimes be made prenatally by ultrasound examination.

Treatment
Treatment of Jarcho-Levin syndrome is sympathetic and supportive. Genetic counseling may be of benefit for families of people with this disorder.
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In 2004, the FDA approved a humanitarian device exemption (HDE) for an implantable metal rod device, usually referred to as the titanium rib, to correct chest wall instability in pediatric patients aged six months to vertebral stability (14 years in girls, 16 years in boys) with thoracic insufficiency syndrome caused by severe deformities of the chest, spine and ribs.

An HDE is a means of offering approval to a device that will be of benefit in diagnosing or treating fewer than 4,000 persons in the USA in any year.

The approval was based on studies led by Dr. Robert Campbell who may be reached at:

Robert Campbell, M.D.
Santa Rosa Children's Hospital
519 West Houston Street
San Antonio, TX 78207
Tel: (210) 704-2988
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McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Spondylocostal Dysostosis, Autosomal Recessive 1, SCDO1. Entry Number; 277300: Last Edit Date; 8/26/2004.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Spondylocostal Dysostosis, Autosomal Recessive 2, SCDO2. Entry Number; 608681: Last Edit Date; 6/4/2004.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Costovertebral Segmentation Anomalies. Entry Number; 122600: Last Edit Date; 3/17/2004.

TEXTBOOK
Jones KL. Ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. W. B. Saunders Co., Philadelphia, PA; 1997:598.

JOURNAL ARTICLES
Whittock NV, Sparrow DB, Wouters MA, et al. Mutated MESP2 causes spondylocostal dysostosis. Am J Hum Genet. 2004;74:1249-54.

Teli M, Hosalkar H, Gill I, et al. Spondylocostal dysostosis: thirteen new cases treated by conservative and surgical means. Spine. 2004;29:1447-51.

Cornier AS, Ramirez N, Arroyo S, et al. Phenotype characterizations and natural history of spondylothoracic dysplasia syndrome: a series of 27 new cases. Am J Med Genet. 2004;128A:120-26.

Kauffmann E, Roman H, Barau G, et al. Case Report: a prenatal case of Jarcho-Levin syndrome diagnosed during the first trimester of pregnancy. Prenat Diagn. 2003;23:163-65.

Tubbs RS, Wellons JC3rd, Blount JP, et al. Jarcho-Levin syndrome. Pediatr Neurosurg. 2002;36:279.

FROM THE INTERNET
Letts RM, Jawadi AH, Congenital Spinal Deformity. emedicine. Last Updated: September 16, 2004. 32pp.
www.emedicine.com/orthoped/topic618.htm

Jarcho-Levin Syndrome. Orphanet. January 2004. 1pp.
www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2311

The Titanium Rib Project. nd. multiple.
http://www.titaniumribproject.8m.com/