Identifying the Genetic Cause of Malformation Can Be Very Challenging

Our comprehensive and rapid genetic diagnostics provide you with actionable results for inherited malformation and retardation syndromes.

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  1. Malformation

Genetic Testing for Malformation and Retardation Syndromes

Our genetic testing and medical expertise provide the most effective combination to understand the underlying causes of malformation and retardation syndromes.

Symptoms related to a genetic cause

Congenital malformations (“birth defects”) remain a leading cause of infant mortality and childhood morbidity. Birth defects can be inherited, including errors of morphogenesis, epigenetic modifications on a parental germline (i.e. the effect of the environment on gene expression), or a chromosomal abnormality. The prevalence of structural birth defects varies globally1, ranging from approximately 3% to 6% of all live births. Most structural birth defects develop early in embryogenesis, during the first ten weeks of pregnancy, and the majority of these defects occur in isolation affecting only one organ system2.

Common features include a cleft in the lip or palate, abnormal facial features, limb or skeletal abnormalities, intellectual disability and delayed growth and development.

Referral reasons

  • Individuals with presentation of the most common disorder

  • Individuals with a positive family history 

  • Individuals without a positive family history but with symptoms resembling the specific disease indication

  • Individuals with a negative but suspected family history in order to perform proper genetic counseling (prenatal analyses are recommended in families with affected individuals)

Diagnostic strategy

Confirmation of a clinical diagnosis through genetic testing allows for genetic counseling and may lead to immediate medical management. For each presented case and phenotype, a full medical report will be produced including a tailored diagnostic strategy, recommendations and a differential diagnosis, if applicable.

What do we know about malformation and retardation syndromes?

Malformation and retardation syndromes are a broad group of different disorders, characterized by inborn abnormalities of the body and organ growth and development.

The majority of inborn malformations are caused by gene defects. The most prevalent defects are orofacial clefts, heart, neural tube and limb defects3. Malformations can present as part of a complex syndrome, typically caused by mutations in several genes, or they can be isolated and associated with a mutation in a single gene.

Most major malformations are non-specific to a particular syndrome, and because they display a broad spectrum of skeletal, neurological, cardiological and other clinical features, getting a correct diagnosis, including identification of any genetic component, in order to start the available treatment is challenging but essential to maximize effectiveness of any intervention.

An accurate and early syndromic diagnosis of congenital malformations is of vital importance, as late diagnosis can result in a delay in intervention and treatment of accompanying anomalies such as congenital heart defects or endocrine disorders.



Single Gene Analysis


What can CENTOGENE do for you and your patients?

CENTOGENE has identified genetic variants associated with malformation and retardation syndromes in more than 450 different genes.

CentoMD® is the world’s largest mutation database for rare diseases, 57% of which is made up of unpublished variants. We carefully curate and document all variants that have clinical relevance for related symptoms, allowing the most comprehensive diagnosis of a reproductive disease.

  1. Christianson A, Howson CP, & Modell B. March of Dimes global report on birth defects: the hidden toll of dying and disabled children. 2006. White Plains: March of Dimes.
  2. Hobbs CA, Chowdhury S, Cleves MA, Erickson S, MacLeod SL, Shaw GM, Tycko B (2014). Genetic epidemiology and nonsyndromic structural birth defects: from candidate genes to epigenetics. JAMA pediatrics, 168(4), 371-377.
  3. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Correa A (2010). Updated national birth prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Research Part A: Clinical and Molecular Teratology, 88(12), 1008-1016.

Scientific Articles on malformation and retardation syndromes

  • A Novel Genetic Syndrome

    Standard genome-scale diagnostics fail to identify a pathogenic variant in up to 50% of patients. CENTOGENE’s free-of-charge ‘research analysis’ of such cases frequently provides strong evidence for yet undescribed gene-disease associations. As a recent example, bi-allelic loss-of-function variants…

  • Disease relevance of alternative splicing

    Alternative splicing of genes usually generates several isoforms. These may code for slightly differing proteins, the disease relevance of which is often not clear. Researchers from CENTOGENE, by reporting a representative example, emphasized the resulting challenges in a recent study. They…

  • Fetal exome sequencing in a real world setting

    Fetal exome sequencing (fES) has been available for some time, but systematic analyses of the outcome are scarce. Based on a series of cases evaluated at CENTOGENE, diagnostic yield of fES was found to be impacted by (i) presence of ultra-sound abnormalities, (ii) positive family history, and (iii)…

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