© 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

Background: 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: Early Infantile Encephalopathy with Epilepsy (EIEE) which has a prevalence of approximately 1 in 50,000 to 1 in 100,000.

The diagnosis of Early Infantile Encephalopathy with Epilepsy (EIEE) represents a diagnostic dilemma for the clinician as the symptoms overlap several other syndromes; some more amenable to treatment than others.

The presentation of epilepsy in combination with multiple other symptoms and as a component of many syndromes with or without encephalopathy represents a diagnostic dilemma.

There are multiple panels which are available to evaluate gene mutations including STXBP1 gene mutations which might provide a definitive diagnosis.

Epilepsy panels looking at 53 or 65 genes or larger panels studying 189 genes are often ordered to include the STXBPI gene which may have as many as 85 mutations to explain the multiple symptoms and variable severity.

Included in many of the panels are mutations which help diagnose:

  • West Syndrome
  • Lennox Gaustaut Syndrome
  • Dravet Syndrome
  • Rett Syndrome or Atypical Rett Syndrome
  • Ohtahara Syndrome

Treatable disorders often confused with STXBP1 mutations may include the following and others:

  • Pyridoxine-Dependent Epilepsy
  • Biotinidase Deficiency
  • Glucose Transporter 1 Deficiency
  • Holocarboxylase Synthetase Deficiency
  • Creatine Deficiency Syndromes
  • Serine Biosynthesis Disorders

Virtually all of the cases of STXBP1 have been sporadic with no family recurrence.

The possibility of gonadal mosaicism exists posing a very small risk for recurrence