Tag Archives: #raregeneticdiseases

Weaver Syndrome

© 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

Weaver Syndrome which is very rare, also called Weaver-Smith Syndrome is characterized by:

  • Fetal & post-natal overgrowth
  • Loose skin
  • Hernias
  • Possible increased risk for neuroblastoma
  • Tall Stature
  • Autism
  • Developmental Disability

Most cases have been attributed to mutations in the EZH2 gene on chromosome 7q36.

Mutations in the NSD1 gene on chromosome 5q35.2-35.3 have been described is several overgrowth syndromes including Sotos Syndrome or Sotos-like Syndrome including Weaver Syndrome.

Weaver Syndrome is believed to be sporadic but inherited in an autosomal dominant inheritance (50%) has been described.

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. Weaver 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 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:  http://www.childgrowthfoundation.org/default.aspx?page=weaversyndrome 

Russell Silver Syndrome

© 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

Definitions:

  • Imprinting of Chromosomes – Mechanism in which genes are expressed in a manner similar to the chromosome of the parent donating the chromosome.
  • Maternal Isodisomy – Inheritance of both copies of a chromosome from a mother.
  • Methylation of Chromosomes – A process whereby the activity of a DNA sequence is changed without changing the sequence of the DNA.

Russell Silver Syndrome is considered a type of dwarfism and is characterized by:

  • Intrauterine Growth Restriction (IUGR)
  • Short stature

Intelligence is usually normal although learning problems and occasionally Autism-like behaviors may occur.

Body asymmetry may occur and children may have

  • Large head to body ratio
  • Prominent forehead
  • Mild to moderate facial changes

Some patients have maternal isodisomy of chromosome #7 (inheritance of both copies of chromosome #7 from the mother).

Other patients have shown decreased methylation of chromosome 11 affecting imprinting.

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. Russell Silver 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 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.

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.

Resources:  https://www.magicfoundation.org/Growth-Disorders/Russell-Silver-Syndrome/ 

Pigmented Nodular Adrenocortical Disease

© 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

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.

Lymphangioleiomyomatosis

© 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

Lymphangioleiomyomatosis is rare type of lung disease that is more common in women and is characterized by:

  • Learning disabilities
  • Developmental disabilities
  • Autism

Lymphangioleiomyomatosis and Tuberous Sclerosis Type I have been attributed to mutations in the TSC1 gene on chromosome 9q36 or TSC2 gene on chromosome 16p13.3.

Lymphangioleiomyomatosis is believed to be inherited in an autosomal dominant manner (50%). Tuberous Sclerosis Type 1 and Tuberous Sclerosis Type 2 are also inherited in an autosomal dominant manner.

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. Lymphangioleiomyomatosis) 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 environmental, 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://www.thelamfoundation.org/

Guanidinoacetate Methyltransferase Deficiency

© 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

Guanidinoacetate Methyltransferase Deficiency is characterized by:

  • Intellectual disability
  • Hyperactivity
  • Autism-like Behaviors
  • Seizures
  • Occasional balance problems

Mutations in the GAMT gene on chromosome 19p13.3 have been described.

Guanidinoacetate Methyltransferase Deficiency is believed to be inherited in an autosomal recessive manner (25% if both parents are gene carriers).

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. Guanidinoacetate Methyltransferase Deficiency) 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.

Resourceshttps://creatineinfo.org/gamt/ 

Contact GENASSIST™

Fill out my online form.