© 2018, GENASSIST, Inc.

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

Background: On February 23, 2017 the American College of OB/GYN (ACOG) issued a guideline recommending that all healthcare providers should – “Offer All Women Pre Pregnancy Genetic Screening – Testing Partners May Be Considered As Well”.

There are between 4,000 and 20,000 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.

This is a follow-up to September 25, 2015 release: ACOG Release First Ever Guidance on Pregnancy in Women With Genetic Conditions.

Analysis: The healthcare provider is faced with the responsibility of recommending testing which may detect patients who are carriers of 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 even which diseases should be tested for except for those already with recommended (e.g. Cystic Fibrosis, Fragile X, SMA 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 be expected as the number of diseases tested for in a panel increases the greater percentage of “variants of uncertain clinical significance” will increase.

Spinal Muscular Atrophy is a muscle-wasting disease with a carrier frequency of (1 in 40 to 1 in 80) and affects

(1 in 10,000) pregnancies. It is due to a deficiency of a protein caused by a defect (mutation in the Survival Motor Neuron –

SMN gene) on Chromosome #5.

Deletions of another gene on Chromosome #5 (Neuronal Apoptosis Inhibitory Protein- NAIP gene) may place a role in modifying the severity of the disease.

Spinal Muscular Atrophy: Can be inherited in an autosomal recessive manner (25% if both parents are gene carriers). X linked inheritance has also been described. 50% of males will be affected, 50% of females will be carriers.


  • Spinal Muscular Atrophy Type 1: Is the number one genetic disease causing fatality in children under two years of age. Is usually characterized by muscle weakness, weak cry, respiratory and feeding problems.
  • Spinal Muscular Atrophy Type 2: Is usually characterized by onset between ages 7 to 18 months with milder symptoms than Type 1. Lifespan is also decreased with earlier onset of symptoms having a worse prognosis.
  • Spinal Muscular Atrophy Type 3: Is usually characterized by muscle weakness but children can usually stand and walk. Lifespan is often normal.
  • Spinal Muscular Atrophy Type 4: Is usually characterized by adult-onset with muscle weakness and normal lifespan.

*The Spinal Muscular Atrophy carrier screen is available preconconceptionally and prenatally in a variety of panels by different laboratories. Carrier testing can lower the likelihood of the disease but does not rule out the carrier state completely.

There are other types of Spinal Muscular Atrophy caused by mutations in genes other than the Survival Motor Neuron genes on Chromosome #5.