© 2016            

By Keith S. Wexler, MBA, Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, 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

Case Study:

A 32 year old patient who had told her OB/GYN on her medical intake form that she was of Caucasian ancestry was found to be a carrier of Joubert Syndrome Type 2 on a Microarray screening test. The OB/GYN is using Microarray screening on many of his patients as a way to help identify rare autosomal recessive diseases early in pregnancy so that there is time to also screen the partner.

The patient’s partner also described himself as being of Caucasian ancestry. When the Joubert testing on the partner was performed, he was also found to be a carrier of Joubert Syndrome Type 2.

After the patient and her partner were found to be carriers of Joubert Syndrome Type 2, they both contacted their families. After further research, both the patient and her partner discovered that they were of Ashkenazi Jewish ancestry.

  • Joubert Syndrome Type 2 (Cerebelloculorenal Syndrome) is an Ashkenazi Jewish inherited disease with a carrier frequency of (1 in 110) and affects (1 in 48,000) pregnancies.
  • Joubert Syndrome Type 2 (Cerebelloculorenal Syndrome) : Autosomal recessive inheritance (25% if both parents are gene carriers) has been described.
  • Joubert Syndrome Type 2 (Cerebelloculorenal Syndrome) is characterized by decreased muscle tone and coordination, abnormal eye movements and breathing patterns, possible developmental delay and/or seizures, kidney and liver problems.

The patient and her partner were referred to our office for an amniocentesis to confirm or rule out a baby with Joubert Syndrome Type 2.

Amniocentesis was performed and the baby was found to be unaffected with the disease, but was found to be a carrier of a single mutation for Joubert Syndrome Type 2.

*The Ashkenazi Jewish Screen is available in a variety of Panels:

  • Basic Panel – 3 Diseases
  • Expanded Panel – 8 Diseases
  • *Full Panel – 18 Diseases – (One company is running a 3 part Ashkenazi panel that has up to 39 diseases)

*The Full Panel is now also part of many Microarray Panels that can test for over 100 diseases.

The Jewish population is the United States as of 2012 was 6,543,820 making up 2.1% of the entire U.S. population (1).

The Ashkenazi Jewish Inherited Disease Panel was created to help screen for specific ethnic inherited diseases. Preconceptional testing is suggested to help identify or rule-out the parents as being carriers.

(1) US Census Bureau, Statistical Abstract of the United States, 2012

AnalysisPrior to the Microarray screening panels, many of which are screening for over 100 autosomal recessive diseases, this patient and her partner would not have known that they were “silent” carriers of the Joubert Syndrome Type 2 until they delivered a child that was affected with the disease.

It is unlikely that a 33 year old patient would have chosen to have an amniocentesis if all of her Non Invasive Prenatal Testing [NIPT] results came back as “Low Risk”.

The dilemma for healthcare providers is that even if the patient had chosen to have an amniocentesis due to a high risk result on a screening test, testing for Joubert Syndrome Type 2 would not have been included since there was no family history of Joubert Syndrome Type 2 nor did the patient nor her partner know that they were carriers.

Microarray helped unlock a risk for an “ethnic disease” that would not have been detected only a few years ago.

As we head forward in the brave new world of Non Invasive Prenatal Testing and Microarray, we will be performing more chromosome, microdeletion and/or microarray problem focused amniocentesis, rather than amniocentesis traditionally based upon a mother’s maternal age related risk.

However, as with any screening test, that means that women of all ages who are detected as being carriers for rare diseases will have the weigh the risks, benefits and limitations of invasive testing.