Tag Archives: #ultrasoundmarkers

Reproductive Medicine – First Trimester Aneuploidy Screening – Part 1

© 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

OVERVIEW: We have known for years that children with chromosomal abnormalities and some structural abnormalities may demonstrate subtle differences on clinical examination. Likewise, the mother’s age at conception, and the mode of conception [i.e. Invitro Fertilization (IVF) and the use of frozen eggs] can affect the calculated risk for a child with a chromosomal abnormality.

Just as the ethnic background can affect the likelihood of specific disorders (i.e. Cystic Fibrosis, Sickle Cell Anemia, Tay Sachs, Thalassemia etc) these differences can affect the ultrasound findings (e.g. biochemical blood results and fetal nasal bone).

Even with Maternal Fetal DNA testing, “ultrasound markers” will continue to be useful for early fetuses at “risk” in addition to screening for aneuploidy:

  • Crown Rump Length (CRL): Small differences in the CRL can affect risk and should be measured with a fetus in a neutral position.
  • Ductus Venosus: This measurement is also difficult to get at 11-14 weeks gestation. The ductus venosus connects the fetal umbilical cord to the inferior vena cava at the level of the diaphragm. The “a” wave is reversed in 3% of chromosomally normal fetuses and approximately 65% of fetuses with Trisomy 21. It is also associated with cardiac defects.
  • Fetal Heart Rate (FHR): Fetal heart rate is slightly increased in fetuses with Trisomy 21 (Down Syndrome). It may be much higher in fetuses with Trisomy 13 (75% of fetuses with Trisomy 13 have a FHR >175 beats per minutes). Not all labs use FHR in their calculations. Labs that use FHR in their calculations will increase the risk for Trisomy 13 even if the FHR increase is only due to increased fetal movement.
  • Fronto Maxillary Facial Angle: 50% of fetuses with Trisomy 21 have an increased angle which is measured from a line drawn from the upper surface of the palate and interior aspect of the maxilla to the external surface of the frontal bones of the forehead in a midsagital view of the face.
  • Nasal Bone: The fetal nasal bone is visualized at 11-13 weeks in 98% of chromosomally normal fetuses and 35% of Trisomy 21 fetuses. Rescan in one week will usually identify a nasal bone in a chromosomally normal fetus. Visualization of a nasal bone in a fetus in a “face down” position may difficult or impossible.
  • Nuchal Translucency (NT): The NT is increased in 95% of Trisomy 21 fetuses, 70% of Trisomy 18 fetuses, 85% of Trisomy 13 fetuses and 5% of chromosomally normal fetuses. Chromosomally normal fetuses with an increased NT (>3.5 mm) have a higher risk for cardiac defects, musculo-skeletal abnormalities, infections, rare genetic syndromes and fetal death. If an increased NT resolves by 20 weeks gestation, the prognosis is good.

A fetal echocardiogram at 22-24 weeks gestation should be considered in chromosomally normal fetuses with increased NT and all fetuses with chromosomal abnormalities.

Tricuspid Regurgitation: Tricuspid regurgitation may be difficult to measure and is seen in approximately 1% of chromosomally normal fetuses and 55% of fetuses with Trisomy 21. It is also seen in fetuses with cardiac defects. As with fetuses with increased NT, a fetal echocardiogram at 22-24 weeks gestation should be considered.

ANALYSIS:

1st Trimester Aneuploidy Screening & “Ultrasound Markers” are still an important Non Invasive Prenatal Testing [NIPT] tool for the healthcare provider. 1st Trimester screening should continue to be used to help evaluate the “low risk” patient who is not a candidate for Maternal Fetal DNA testing and the “high risk” patient who declines having invasive testing, i.e. CVS or amniocentesis, even when indicated.  

Maternal Fetal DNA testing usually will not identify structural problems unrelated to a chromosomal abnormality. 

Ultrasound Markers – Patau Syndrome

© 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

Patau Syndrome (Trisomy 13) is characterized by three copies of chromosome #13 instead of the expected

two copies.  

The incidence of Patau Syndrome is approximately 1 in 2000 to 1 in 5000 births.

Ultrasound performed in pregnancy after 15 weeks gestation can help identify some babies with Trisomy 13.

Patau Syndrome Ultrasound “Markers:

  • Small Head
  • Small Orbits
  • Sloping Forehead
  • Low Set Ears
  • Cleft Lip/Cleft Palate
  • Extra Fingers and/or Toes
  • Possible Ambiguous Genitalia
  • Occasional Deficiency Development of the Front of the Brain
  • Excess Fluid Accumulation
  • Diaphragmatic Hernia
  • Hernia of Abdominal Wall
  • Heart Defect(s)

(1) The American College of Obstetricians & Gynecologists, Committee Opinion Number 545 December 2012, Publications Committee, “NonInvasive Prenatal Testing for Fetal Aneuploidy”.  The American College of Obstetricians and Gynecologists Committee on Genetics, The Society For Maternal-Fetal Medicine 

Ultrasound – Polycystic Kidneys

© 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:  A patient seen by her healthcare provider for her 20 week Level II ultrasound was found to have bilateral hydronephrosis (accumulating fluid in the kidneys and or collecting systems for the kidneys) of 5 mm.  The healthcare provider referred her to us for a 2nd opinion and a diagnosis of possible Polycystic Kidneys was made by Dr. Wexler.

Patient was referred to Maternal Fetal Medicine for confirmation of kidney and liver cysts.

Polycystic Kidneys and/or Polycystic Kidney Disease (PKD) is inherited in an autosomal dominant (50% risk to first degree relatives) or autosomal recessive manner (25% if both parents are gene carriers).

One of the characteristics of a disease caused by inheritance of a single deleterious gene (autosomal dominant inheritance) is variable severity.  This means that any or all children who inherit the deleterious gene (50% of children) could have milder or more severe problems related to their kidney function. 

Polycystic Kidney Disease has an incidence of approximately1:400 to 1:1000.

Polycystic Kidney Disease  may be acquired.

Most case of PKD are due to one or more mutations in the PKD1 gene on the short arm on chromosome #16 (16p13.3) or the PKD2 gene on the long arm of chromosome #4 (4q21-13). 

If the mutation is identified in the patient then Preimplantation Genetic Diagnosis becomes a possibility.

PKD causes multiple cysts to form in the kidneys and occasionally the liver and rarely the pancreas. Heart valve problems, abdominal wall hernias and intracerebral aneurysms can occur. 

The kidney cysts diminish kidney function eventually resulting in kidney failure.

The condition may be asymptomatic early in the course of the disease but can cause abdominal or back pain, blood in the urine, kidney stones, kidney infection, fatigue, joint pain and skin or nail abnormalities.

At least 400 mutations have been identified in the PKD1 gene responsible for approximately 85% of cases of Polycystic Kidney Disease (Type I) and over 40 mutations have been identified in the PKD2 gene responsible for approximately 15% of cases of Polycystic Kidney Disease (Type II)

Rarely, mutations in a third gene – PKD3 also can result in autosomal dominant PKD.

PKD can affect both the liver and kidneys and can result in serious renal problems either shortening the individual’s lifespan or resulting in kidney transplantation.

Ultrasound Markers – Turner 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

The breakdown of fetal cells in the maternal circulation make it possible for laboratories to screen for Fetal DNA during pregnancy. When fetal cells break down Cell Free DNA (cf DNA) is released.

It is possible to duplicate many copies of this DNA so that testing is possible. This prenatal non-invasive testing can be performed as early as the 10th week of pregnancy.

Turner Syndrome is characterized by a missing X chromosome in females instead of the expected two X chromosomes.

http://www.turnersyndromefoundation.org/

If a Maternal Fetal DNA test result comes back as “High Risk” for a chromosomal abnormality, the recommendation (1) is to confirm the diagnosis by amniocentesis. Ultrasound performed in pregnancy after 15 weeks gestation can help identify some babies with Turner Syndrome.

Ultrasound “Markers” for Turner Syndrome:

  • Increased Nuchal Translucency – NT
  • Cystic Hygroma
  • Micrognathia (small jaw)
  • Short 4th metacarpal
  • Differential diagnosis: Noonan Syndrome
  • Differential diagnosis: 4p+ Syndrome

(1)The American College of Obstetricians & Gynecologists, Committee Opinion Number 545 December 2012, Publications Committee, “NonInvasive Prenatal Testing for Fetal Aneuploidy”.  The American College of Obstetricians and Gynecologists Committee on Genetics, The Society For Maternal-Fetal Medicine

Ultrasound Markers – Trisomy 13

© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, CIO Maternal Fetal Medicine, Prenatal Diagnosis, 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

Trisomy 13 (Patau Syndrome) is characterized by three copies of chromosome #13 instead of the expected two copies.  The incidence of Trisomy 13 (Patau Syndrome) is approximately 1 in 2000 to 1 in 5000 births.

If a Maternal Fetal DNA test result comes back as “High Risk” for a chromosomal abnormality, the recommendation (1) is to confirm the diagnosis by amniocentesis. Ultrasound performed in pregnancy after 15 weeks gestation can help identify some babies with Trisomy 13.

Trisomy 13 (Patau Syndrome) Ultrasound “Markers”:

  • Small Head
  • Small Orbits
  • Sloping Forehead
  • Low Set Ears
  • Cleft Lip/Cleft Palate
  • Extra Fingers and/or Toes
  • Possible Ambiguous Genitalia
  • Occasional Deficiency Development of the Front of the Brain
  • Excess Fluid Accumulation
  • Diaphragmatic Hernia
  • Hernia of Abdominal Wall
  • Heart Defect(s)

(1) The American College of Obstetricians & Gynecologists, Committee Opinion Number 545 December 2012, Publications Committee, “NonInvasive Prenatal Testing for Fetal Aneuploidy”.  The American College of Obstetricians and Gynecologists Committee on Genetics, The Society For Maternal-Fetal Medicine 

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