© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, CIO – 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

Autism Spectrum Disorders – Pigmented Nodular Adrenocortical Disease is characterized by:

  • Bilateral adrenal cortical hyperplasia
  • *Cushing Syndrome
  • Hear impairment
  • Occasional Autism Spectrum Disorder behaviors

*Cushing Syndrome is a hormonal disorder caused by prolonged exposure to elevated levels of cortisol produced by the adrenal glands. It can be caused by excess production of cortisol from the adrenal glands or by administration of high levels of cortisol.

Cushing Syndrome symptoms can include:

  • High blood pressure
  • Bone loss
  • Type 2 diabetes
  • Weight gain
  • Stretch marks
  • Increased body hair
  • Bruising

Mutations in the PDE8B gene NSD1 on chromosome 5q13 or PD11A gene on chromosome 2q31 or the PRKAR1A gene on chromosome 17q23-24 have been described with the disorder.

Pigmented Nodular Adrenocortical Disease is believed to be inherited in an autosomal dominant manner (50%).

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. Pigmented Nodular Adrenocortical Disease) 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.

Resources:https://csrf.net/