Tag Archives: #genetictesting

Reproductive Medicine – Canavan Disease

© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, Business Development Director, Life Sciences, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital


  • Microarray: Computerized analytic system for looking for specific DNA fragments associated with specific diseases (e.g. Spinal Muscular Atrophy or Tay Sachs).

Canavan Disease is a common Ashkenazi Jewish inherited disease with a carrier frequency of (1 in 40) and affects (1 in 6400) pregnancies.

Canavan Disease: Autosomal recessive inheritance (25% if both parents are gene carriers) has been described.

Canavan Disease is a fatal metabolic blood disease usually detected by age 18 months and is characterized by brain deterioration.

It is estimated that there are between 4,000 and 20,000 diseases (with over 7000 rare genetic diseases) and several companies are offering screening panels for the carrier state of several hundred conditions and the possible predisposition for various cancers including some hematologic and neurologic malignancies.

Rare Disease affects 1 in 2000 people. 7% of the population will be affected with a rare disease in the lifetime.

Rare Genetic Disease affects 1 in 200,000 people. The registry established that there are an average of 4200 cases per Rare Disease. National Organization of Rare Diseases established 1983 by Abbey Meyers and others got Orphan Drug Act passed 1983.

Analysis: One of the greatest dilemmas facing the healthcare provider is when a family presents with a positive family history of a very rare genetic disease and/or syndrome (e.g. Canavan Syndrome) and the family wants to know from the healthcare provider:

  • Whether the disease and/or syndrome is inherited (autosomal dominant manner (50%), autosomal recessive (25% if both parents are gene carriers) or sex (X) linked (50% of males will be affected, 50% of females will be carriers), multifactorial (interaction of multiple genes with the environment, both genetic and non-genetic factors)?
  • Whether the disease and/or syndrome is sporadic (due to a new mutation) and might or might not reoccur in a family?
  • Whether the disease is caused by a Microdeletion?
  • Whether there is testing for the disease and/or syndrome?
  • If there is testing, is prenatal diagnosis and/or Preimplantation Genetic Diagnosis (PGD) available?

Furthermore, if screening and/or testing is available, the healthcare provider has the responsibility of deciding whether to recommend testing which may or may not detect patients who are carriers or affected with one or more disorders.

If a test returns as “carrier” most conditions identified will require testing the partner since the majority of the conditions tested for are inherited in an autosomal recessive manner [inheritance of one disease causing (deleterious) gene from each parent].

Since not all screening laboratories are contracted with insurance companies and panels currently offered may screen from 3 to 250 diseases, the healthcare provider will need to decide which tests to order and which laboratory to use.

However, the ACOG guideline does not set up a specific pre pregnancy panel nor recommend how many diseases or which diseases should be tested for except for those already recommended [e.g. Cystic Fibrosis, Fragile X, Spinal Muscular Atrophy (SMA), some “ethnic” panels, etc.].

Some laboratories are now offering “customized” panels developed by the healthcare provider in consultation with the laboratory based on the individual’s personal and family history and background.

With the increasing availability of such panels and the reduction in the cost, the demand for larger panels and the need for interpretation of laboratory results for the healthcare provider and the patient will continue to increase.

Likewise, it can also be expected as the number of diseases tested for increases, a greater percentage of “variants of uncertain clinical significance” will also increase.

Interpretation, explanation and additional recommendations for monitoring and follow-up of the individual screened and other family members will also be required.

Reproductive Medicine – 22q11.2 Deletion Syndrome (DiGeorge Syndrome)

© 2018, GENASSIST, Inc.           

By Keith S. Wexler, MBA, CFO, Business Development Director Life Sciences, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background:  We saw a 36 year old female with one healthy child at approximately 10 weeks gestation who tested “High Risk”(1 in 20) for a having a child with 22q11.2 Deletion Syndrome.

Prior to Maternal Fetal DNA screening tests or microarray in pregnancy, the only way that a patient would know if they had child with a microdeletion was at delivery with an “affected” child.

DiGeorge Syndrome (22q11.2 Deletion Syndrome): Is characterized by heart problems, kidney problems, and/or immune system problems, movement problems and seizures. This syndrome is caused by a loss or rearrangement of a small portion of the long arm of chromosome #22 [22q11.2].

  • Approximate Incidence – 1 in 2,000 births.

The 22q11.2 Deletion Syndrome has several names attributed to it because of the variability of the presentation. The syndrome has also been called Velocardiofacial Syndrome describing involvement of the palate, heart and face, Shprintzen Syndrome or DiGeorge Syndrome.


Findings can include:

  • cleft palate
  • hearing, speech and learning problems
  • facial changes including small chin
  • low set ears and wide set eyes
  • delayed growth and feeding difficulties
  • poor muscle tone,
  • heart defects such as interrupted aortic arch, common outlet for aorta and pulmonary arteries, ventricular septal defect or Tetralogy of Fallot
  • frequent infections due to hypoplasia of the thymus
  • low calcium due to hypoparathyroidism
  • decreased kidney function.

Approximately 10% of 22q11.2 deletion syndrome cases are familial being inherited from a parent who might have mild symptoms or be unaware of the 22q11.2 deletion in one of their #22 chromosomes.

Approximately 90% of cases are due to a new deletion in that individual and will place each of their children at a 50% (1:2) risk of inheriting the deleted chromosome #22.

“Routine” screening for Microdeletions on all patients is controversial because of the low prevalence of these disorders and the possibility of “false positive” and “false negative” results.

However, when a patient is identified as a candidate for invasive testing i.e. Chorionic Villus Sampling (CVS) and/or amniocentesis, the addition of Microdeletions may be indicated, particularly if family history or ultrasound findings suggest an increased possibility for detection of one of these rare disorders.

Reproductive Medicine – Universal Screening vs Ethnic Screening

© 2018, GENASSIST, Inc.    

By Keith S. Wexler, MBA, CFO, Business Development Director, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Overview: The United States prides itself as a multicultural multiethnic society. The medical community attempts to classify certain disorders by ethnic origin. The racial, religious and cultural diversity among the population makes the concept of screening on the basis of “ethnicity” alone a naïve concept.

GENASSISTTM  is contacted by a carrier parent(s) or patients with a first degree family member who is found to be a carrier for a disease that is more common in a specific ethnic group using DNA/Microarray screening that can screen patients for hundreds of diseases.

Single ethnic screening tests for Sickle Cell Anemia, Alpha or Beta Thalassemia, Tay Sachs Disease, Cystic Fibrosis, Canavan Disease are being replaced by more comprehensive panels. With traditional “ethnicity” screening:

  • Black/African Americans are screened for Sickle Cell Anemia
  • Ashkenazi Jews for Tay Sachs or Canavan Disease
  • Caucasians for Cystic Fibrosis
  • Greeks/Italians for Beta Thalassemia

Yet we know that French Canadians and Cajuns have a high incidence of Tay Sachs, Saudi Arabians have a high incidence of Sickle Cell Disease and Asians and Pacific Islanders have a high incidence of Alpha Thalassemia. Also, many couples when questioned are either unsure or have no knowledge of their ethnic background or define themselves as multiracial and/or multiethnic.


Over the past 10-20 years the prohibitive costs of screening for carriers of various autosomal recessive diseases made consideration of more expanded screening untenable.

With single disease screening varying in cost from $250 to $350 per disease, patients and healthcare providers appropriately limited the number of disorders screened for or decided against the type of screening altogether.

Likewise, insurance companies have either been unwilling or reluctant to cover “ethnic screening” except for the most basic, due to the cost.

The Ashkenazi Screen that screens for 18 diseases that are the most common in the Ashkenazi Jewish population previously cost almost $6000 for the entire panel.  

Many insurance companies will only pay for a limited panel (e.g. Tay Sachs, Canavan Disease and Cystic Fibrosis etc).  Since November 2017, many insurance companies are requiring a “Pre Determination Genetic Letter” from a physician, prior to testing” to decide whether or not the insurance will pay for testing.

Patients could have the expanded panel but insurance might not pay for the additional diseases unless an affected family member with a specific disease or a known carrier was identified. Therefore, the cost of screening possible “carrier” patients was financially prohibitive for most patients.

Following the trend toward safer and more accurate Non Invasive Prenatal Testing, [NIPT] more healthcare professionals are working with Microarray companies to make “Universal” carrier screening available to their patients.

Microarray is defined as a DNA platform that uses probes to identify critical sites along the genome associated with specific diseases. These Microarray technological breakthroughs now allow patients to screen for many diseases from A (Alpha-1 Antitrypsin Deficiency) to Z (Zellweger Spectrum Disorders) for a fraction of the cost.

Analysis: Universal Microarray “ethnic” screening panels are reliable, available and cost effective.

Although we cannot screen for “everything”, the panels allow increased screening for more of the disorders that can seriously impact the health of the child.

Also, the cost of screening is now within reach of most families.  With carrier frequencies as high a 1:25, now is an appropriate time to review our approach.

GENASSIST Linear Profile Rare Genetic Diseases


GENASSIST Linear Profile Rare Genetic Diseases 



GENASSIST Linear Profile Pediatrics


GENASSIST Linear Profile Pediatrics


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