• Register
  • Login
  • Bookmark this page!
Skip Navigation LinksHome Page    >    Tests during the pregnancy    >    Irregularities or Defects in the Structure of the Vertebrae
 
 
Pregnancy links...
Health links...
Genetics links...
Medical links...
Autism links...
Other links...
 

Irregularities or Defects in the Structure of the Vertebrae


Types

Many variations may occur in the structure of the vertebrae, and it is important to distinguish between these:
  • Usually the defect is restricted to a single vertebra without other abnormalities. It is important to differentiate between the different types of defect:
    • Defects involving a triangular rather than quadratic vertebra (hemivertebra) or an abnormal, butterfly-shaped structure, etc., are common.

    • Annular (ring-shaped) vertebral defect.



  • Less commonly the defects involve a number of vertebrae and there may be defects in other organs as well. There are a number of major types of varying severity:
    • Spondylocostal dysostosis

    • Spondylothoracic dysplasia

    • If there are defects in other organs as well, genetic syndromes, chromosomal problems and other causes must also be considered.

Clinical signs

A defect limited to only one vertebra without other abnormalities:
  • A hemivertebra or butterfly-shaped vertebra, etc., may lead to lordosis - this condition can be corrected relatively effectively. These defects can occur as a result of disruption in intrauterine development or from genetic causes. Sometimes there is an association with other defects including those of the kidney and thumb, heart defects, congenital anal atresia (blockage), and congenital intestinal atresia. The combination of these is called the VACTER (Vertebral, Anal, Cardiovascular, Tracheoesophageal, Radial) association and it is more common in twin pregnancies.

  • An annular vertebral defect, where the vertebra is narrow, may -choke- and interfere with the development of the spinal cord running inside it. These cases are more difficult to correct surgically, especially if the stenosis (narrowing) of the ring is severe, in which case the pressure on the spinal cord is high.

Defects in a large number of vertebrae and/or the presence of defects in other organs as well. Here the problem is more complex, and there are a number of major types of varying severity:
  • Spondylocostal dysostosis - this manifests as a focal disorder of the vertebrae only and many vertebrae have an abnormal structure. It is accompanied by a shortening and marked lordosis of the trunk. Over the years there is a stiffening of the trunk, probably because of reduced mobility, which is usually a result of backache. There are mutations in the genes responsible for intrauterine development, which cease acting after birth. This means that the condition does not progress.

  • Spondylothoracic dysplasia - this is a more severe type of defect in the structure of the vertebrae that is accompanied by very severe disruption of the growth of the trunk. The defect here is in genes that are expressed after birth as well, therefore there is worsening and progression over the years. Here, there may also be defects in other organs, such as the kidneys, urinary bladder and the structure of the brain, and other associated abnormalities including congenital anal atresia, cleft palate, etc. These children usually die during infancy because of their small chest and resulting respiratory failure.

  • It is less common to find defects in other organs, but in such cases genetic, chromosomal and other syndromes should be considered. The clinical manifestations and implications depend on the specific syndromes. There are also focal disorders in a number of vertebrae that are transmitted by autosomal dominant inheritance - these are usually less severe.

Inheritance pattern

When the defect is restricted to a single vertebra, the condition is usually not hereditary.

When the problem involves a number of vertebrae and/or defects in other organs, the heredity depends on the specific condition.

In spondylocostal dysostosis, the pattern of inheritance is autosomal dominant.

In spondylothoracic dysplasia, the pattern of inheritance is autosomal recessive.

When there are defects in other organs, the pattern of inheritance depends on the specific syndrome.

Penetrance

  • When the defect is restricted to only one vertebra - unknown.

  • When there are abnormalities in a number of vertebrae and/or the presence of defects in other organs as well, the penetrance depends on the specific syndrome. In spondylocostal dysostosis and spondylothoracic dysplasia the penetrance is usually complete.
    When there are defects in other organs, the degree of expression depends on the specific syndrome.

Associated features that can be demonstrated in tests performed during pregnancy

In the case of a triangular vertebral defect (hemivertebra) or butterfly-shaped defect, etc., there is sometimes an association with other defects including those of the kidney and thumb, heart defects, congenital anal atresia (blockage), and congenital intestinal atresia. The combination of these is called the VACTER association and it is more common in twin pregnancies. It is therefore important to perform ultrasound testing directed specifically at all these areas.

In spondylocostal dysostosis, there are usually no associated defects, but it is worth checking for all the VACTER association defects and those detailed above under spondylothoracic dysplasia, especially defects in the kidneys, urinary bladder and the structure of the brain, and other associated abnormalities including anal atresia, cleft palate, etc. These children usually die during infancy because of their small chest and resulting respiratory failure. In cases of multiple vertebral defects, with or without other abnormalities, chromosome analysis of amniotic fluid in the fetus or of blood in the neonate should be carried out.

In all these cases it is important to refer the couple for genetic counseling, to which they should bring all data, including the results of other tests performed during the pregnancy such as alpha-fetoprotein, nuchal translucency, detailed ultrasound findings, etc.

It is also advisable to refer the parents to a multidisciplinary clinic in a hospital for professional counseling by a geneticist, an expert in ultrasound examinations, a pediatric orthopedist, and a neonatologist, in order to collate all the data and discuss the various risks in each specific case, the method of monitoring the fetus, possible intervention if indicated, etc. The decisions taken will depend on the severity of the problem, the presence of additional findings, etc.

What is the risk of recurrence in a subsequent pregnancy?

  • When the defect is restricted to just a single vertebra, and there is only one case in the family, it is usually not hereditary, and the risk of recurrence is low.

  • When the condition involves a number of vertebrae and/or other organ defects:
    • In spondylocostal dysostosis, a parent with this condition has a 50% chance of having a child with the same condition.

    • In spondylothoracic dysplasia, parents who have had a child with this condition have a 25% risk in every pregnancy of having another affected child.

  • When there are defects in other organs, the risk of recurrence depends on the specific syndrome.

For more distant relatives, the risk can be determined within genetic counseling based on the cause of the defect in the spinal column, the pedigree, and the results of tests such as chromosome analysis, etc.

Molecular genetic information

The gene for the disease

When the defect is limited to only one vertebra, the gene is not known.

In spondylocostal dysostosis - the DLL3 gene.

In spondylothoracic dysplasia - not known at the present time.

When there are defects in other organs as well - depends on the specific syndrome.

Location

In spondylocostal dysostosis - the DLL3 gene is situated on chromosome 19p13.

In spondylothoracic dysplasia - not known at the present time.

Genetic testing

Diagnostic testing

For spondylocostal dysostosis - testing for DLL3 gene mutations.

For spondylothoracic dysplasia - not available at the present time.

Carrier testing

In spondylocostal dysostosis - carrier testing can only be performed in a family in which there is already an affected child by direct or indirect testing. If the mutation is found in the affected child, the DLL3 gene mutation test can be used. If there was an affected child in a previous pregnancy and the mutation responsible for the disease has not yet been found, genetic markers linked to the DLL3 gene on chromosome 19p13 can be used.

In spondylothoracic dysplasia - not yet possible.

Fetal testing

In spondylocostal dysostosis - if the mutation has been found in an affected child in the family, the DLL3 gene mutation test can be used. If there was an affected child in a previous pregnancy and the mutation responsible for the disease has not yet been found, genetic markers linked to the DLL3 gene on chromosome 19p13 can be used.

In spondylothoracic dysplasia - not yet possible.
 
Haven't found what you're looking for? Search for it here:   
Comments (0)





Leave a Comment
Name
Email (will not be published)
Website (optional)
Subject
Your Comment

Line and paragraph breaks are automatic.

Please type the characters you see in the picture:


All content Copyright © 2009-2011, Genetics of Pregnancy Encyclopedia Corporation. All rights reserved.