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Jarcho-Levin Syndrome

Last updated Oct. 17, 2018

Approved by: Maulik P. Purohit MD, MPH

Jarcho-Levin Syndrome (JLS) is a genetic disorder characterized by abnormalities in the development of bones in the vertebral column and ribs, such that these deformations in the torso, give a characteristic “crab-like” or “fan-like” appearance to the bones. This condition is more prevalent among the Puerto Rican population.


What are the other Names for this Condition? (Also known as/Synonyms)

  • Short Trunk Dwarfism
  • Spondylocostal Dysostosis
  • Spondylothoracic Dysplasia

What is Jarcho-Levin Syndrome? (Definition/Background Information)

  • Jarcho-Levin Syndrome (JLS) is a genetic disorder characterized by abnormalities in the development of bones in the vertebral column and ribs, such that these deformations in the torso, give a characteristic “crab-like” or “fan-like” appearance to the bones. This condition is more prevalent among the Puerto Rican population
  • Jarcho-Levin Syndrome is manifested before or after birth, with malformations of the ribcage and spine, a short trunk, short neck, and distinctive facial features. Although the legs and arms are normal in size, the affected individuals have a short stature. The characteristic features of JLS aid in its diagnosis as well
  • The skeletal abnormalities can cause improper development and crowding of internal organs, leading to complications such as breathing difficulties, pneumonia, and hernia
  • Mutations(s) in the DLL3, MESP2, and LFNG genes cause Jarcho-Levin Syndrome. These genes are involved in the regulation of the Notch signaling pathway (a cell signaling system), which regulates boundaries during embryonic development, including the separation of vertebrae from each other
  • Treatment for the condition mostly involves providing relief from the symptoms and preventing any complications from developing. The treatment measures may include medications for infections and surgery for bone deformities
  • Presently, there are no methods or guidelines to prevent Jarcho-Levin Syndrome from occurring. Genetic counseling may aid prospective parents with a family history of this syndrome, to make suitable informed decisions
  • The outcome of Jarcho-Levin Syndrome is determined by the severity of symptoms. Individuals with the disorder may lead healthy lives, if the symptoms are mild. However, if lung abnormalities cause respiratory insufficiency, then the prognosis may be poor. In such cases, the affected children may succumb to the condition

Who gets Jarcho-Levin Syndrome? (Age and Sex Distribution)

  • Jarcho-Levin Syndrome is an inherited disorder affecting one in 200,000 individuals. JLS is typically manifested during gestation or soon after birth
  • The condition occurs worldwide. However, individuals of Spanish and Puerto Rican descent are known to have an increased susceptibility to the syndrome, with an incidence rate of one in 12,000
  • Both male and female genders may be equally affected by this disorder

What are the Risk Factors for Jarcho-Levin Syndrome? (Predisposing Factors)

Jarcho-Levin Syndrome is an inherited disorder. The following are some known risk factors for JLS:

  • A family history of the disorder
  • Puerto Rican ancestry: People belonging to this ethnic group and ancestry are more susceptible to this condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Jarcho-Levin Syndrome? (Etiology)

Jarcho-Levin Syndrome is caused by mutation(s) in the MESP2, DLL3, and LFNG genes.

Involvement of the MESP2 gene:

  • Under normal circumstances, this gene codes for a transcription factor called MESP2 protein. A transcription factor binds to DNA and regulates expression of specific genes
  • The MESP2 protein regulates expression of some genes in the Notch signaling pathway by blocking the NOTCH1 protein
  • This pathway is involved in a complex process known as somite segmentation. This process separates the future vertebrae in the developing embryonic tissue
  • A mutation in MESP2 gene causes aberrant protein, interfering with defining boundaries for vertebrae via somite segmentation. This causes the bones to fuse during development

Involvement of the DLL3 gene:

  • Similar to MESP2, the DLL3 gene is also involved in the Notch pathway during embryonic development
  • The DLL3 gene codes for a protein that binds NOTCH1 protein, marking it for destruction
  • The destruction of NOTCH1 protein allows somite segmentation and definition of boundaries between future vertebrae to occur normally
  • A mutation in the DLL3 gene causes abnormalities in the protein function, leading to non-destruction of NOTCH1 protein. This leads to the fusion of bones in the developing embryonic tissue

Involvement of the LFNG gene: 

  • The LFNG gene is a member of a family of genes known as “fringe gene family”. The genes in this family code for enzymes (known as glycosyltransferases) involved in the Notch pathway, similar to MESP2 and DLL3 genes
  • When mutated, the specific enzyme coded by LFNG is abnormal, leading to aberrant signaling in the Notch pathway
  • This causes obscuring of boundaries between future vertebrae in the developing embryo, causing fusion of bones

All three genes responsible for Jarcho-Levin Syndrome are inherited in an autosomal recessive pattern. In this type of inheritance, an individual must possess both copies of the causative gene in the defective form in every cell of his/her body for the condition to manifest itself. An affected individual inherits one defective copy from each parent. The parents are carriers of the condition and are generally not affected.

Based on the number of bones involved and severity of symptoms, Jarcho-Levin Syndrome is classified into two major types:

  • Spondylocostal Dysostosis Type 1 (SCDO1): A severe form of the disorder with deformity and fusion of all vertebrae
  • Spondylocostal Dysostosis Type 2 (SCDO2): This type is milder than SCDO1, and not all vertebrae are fused or abnormal

What are the Signs and Symptoms of Jarcho-Levin Syndrome?

The following are some signs and symptoms of Jarcho-Levin Syndrome:

  • Malformation of the spinal bones
    • Outwards curving of the spine (kyphosis)
    • Inward curving of the spine (lordosis)
    • Sideways curving of the spine (scoliosis)
  • Short torso and small stature
  • Fusion and underdevelopment of ribs causing a cavity in the chest
  • Short neck; limited range of movement in the neck
  • Webbed fingers (syndactyly); camptodactyly or long and bent fingers
  • Distinctive facial features such as:
    • Broad forehead
    • Wide nasal bridge
    • Upward turned nostrils
    • Slanted eyelids
    • Enlarged skull (posterior skull enlargement)
  • Underdeveloped lungs; repeated lung infections, pneumonia
  • Distended stomach or pelvis
  • Presence of two uteri in females
  • Undescended testicles and absence of external sex organs in males
  • Abnormalities in the central nervous system
  • Cognitive difficulties

How is Jarcho-Levin Syndrome Diagnosed?

The diagnosis of Jarcho-Levin Syndrome is made on the basis of the following tests and exams:

  • Physical examination, when the characteristic features of the disorder are examined
  • An evaluation of family medical history
  • Imaging tests of the spine and vertebrae using ultrasound scans or X-ray
  • In pregnant women with a family history of the disorder, an ultrasound examination of the fetus may be conducted

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Jarcho-Levin Syndrome?

The following complications may occur in individuals with Jarcho-Levin Syndrome:

  • Respiratory problems and breathing difficulties, episodes of pneumonia
  • Hernias
  • Neural tube defects
  • A small chest which is unable to accommodate the growing lungs, leading to severe respiratory insufficiency (acute respiratory distress syndrome); such a complication is often fatal

How is Jarcho-Levin Syndrome Treated?

The treatment measures for Jarcho-Levin Syndrome may include:

  • Antibiotics for repeated lung infections
  • Use of vertical expandable prosthetic titanium rib (VEPTR): This is an implanted device that helps the bones in the chest cavity to expand and straighten, so the lungs can grow
  • Surgical repair of affected bones

How can Jarcho-Levin Syndrome be Prevented?

  • At the current time, there are no methods or guidelines available for the prevention of Jarcho-Levin Syndrome, since it is a genetic disorder
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited genetic disorders such as Jarcho-Levin Syndrome

What is the Prognosis of Jarcho-Levin Syndrome? (Outcomes/Resolutions)

  • The prognosis of Jarcho-Levin Syndrome is determined by the severity of symptoms; specifically, the extent of narrowing of the chest cavity
  • Individuals with milder form of the disorder may live up to adulthood
  • In babies born with severe fusion of rib bones, the inability of lungs to grow and fill with air may cause respiratory insufficiency, which can be fatal (usually within 15 months of birth)

Additional and Relevant Useful Information for Jarcho-Levin Syndrome:

Jarcho-Levin syndrome is also known by the following additional synonyms:

  • Costovertebral Anomalies
  • Costovertebral Dysplasia
  • Costovertebral Segmentation Anomalies
  • Hereditary Malformations of the Vertebral Bodies
  • Hereditary Multiple Hemivertebrae
  • Occipito-Facial-Cervico-Thoracic-Abdomino-Digital Dysplasia
  • SCDO1
  • SCDO2
  • Spondylothoracic Dysostosis
  • Syndrome of Bizarre Vertebral Anomalies

There are some reports of a classification based on whether the condition is autosomal recessive or autosomal dominant. While most cases of Jarcho-Levin Syndrome are inherited in an autosomal recessive manner, some types of Spondylocostal Dysostosis are inherited in an autosomal dominant manner. It has been reported that the autosomal recessive form is identifiable prenatally, has serious bone deformities, and is generally marked by high mortality rates.

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: July 10, 2017
Last updated: Oct. 17, 2018