© 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

Noonan Syndrome is sometimes referred to as male Turner Syndrome.

Noonan Syndrome is often diagnosed at birth or in early childhood.

Noonan Syndrome findings are variable but may include:

  • Webbed neck
  • Short stature
  • Low posterior hairline
  • Posteriorly rotated low set ears
  • Pectus excavatum
  • Blood disorders
  • Heart defects (often pulmonary stenosis and/or hypertrophic cardiomyopathy)
  • Kyphoscoliosis
  • Epicanthal folds
  • Widely spaced eyes (hypertelorism)
  • Cystic hygroma

Noonan Syndrome is inherited in an autosomal dominant manner and mutations in multiple genes have been described. *Up to 50% of individuals with Noonan Syndrome have a new mutation which causes the syndrome.

*Prenatal diagnosis may be an option if the mutation is known. Up to 25% of individual with Noonan Syndrome will Not be diagnosed with molecular testing.

The remainder of Noonan Syndrome cases are inherited from a parent who may manifest more severe or milder findings.

Males are more commonly affected than females.

Up to 1/3 of individuals with Noonan Syndrome may have problems suggestive of Austistic-like behaviors including:

  • Speech problems
  • Motor problems
  • Hearing loss
  • Learning problems
  • Attention problems

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.

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. Noonan 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 there is testing for the disease and/or syndrome

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.

[*A recent study, that is ongoing, has suggested a possible relationship between maternal age (35 years or older) and/or paternal age (greater than 40 years) and autism and/or autism spectrum disorder(s) in a child. Reference: Israel & Mt. Sinai, NY. *Some recent studies have suggested risk may be as high as 1:50 to 1:80.]