Genetics for Maternal Child Health Nursing

Brandy M. Freschi (Smolnik), MS, CGCCertified Genetic Counselor

Perinatal Associates of Northern Nevadawww.renoperinatal.com

Ph 775-829-0573 Fax 775-329-8528

Overview

• Genetic Counselors & Genetic Counseling• Prenatal Genetics• Neonatal & Pediatric Genetics• Pregnancy Loss• Grief/Bereavement

Genetic Counselors

• Genetic counselors are health professionals with specialized Master’s degrees and experience in the areas of medical genetics and counseling.

– Accredited by the American Board of Genetic Counseling; require specific competencies, case load/type, and coursework

– Board certification required; Licensure available in only some states• Genetic counselors work as members of a health care team, who provide information and support to families who have

members with or are at risk for birth defects and/or genetic/inherited disorders by:– Identify families at risk– Investigate the problem present in the family– Interpret information about the disorder– Analyze inheritance patterns and risks of recurrence– Review available testing and treatment options with the family

• Genetic counselors also:– Provide supportive counseling to families– Serve as patient advocates– Refer individuals and families to community or state support services.– They serve as educators and resource people for other health care professionals and for the general public

• Settings:– Prenatal, Pediatric/Adult, Cancer, Laboratory, Research, Specialty Disease Clinics, etc.

• Non-directiveness– Unique from other disciplines/settings in health care– Important because genetics often involves reproductive decisions which are made involving many factors:

• Magnitude of risk• Burden of impact of disorder• Individual perception of impact• Meaning of children• Individual cultural, religious or personal preferences

Why is Genetics Important in Maternal Child Health Nursing?

• Incidence of chromosome abnormalities - 1/200

• 40-60% of admissions to children hospitals are for genetic or genetic related conditions

• Thousands of genetic conditions exist with new ones discovered regularly

• Majority of all deaths have a genetic component

Prenatal Genetics

Indications for a GeneticCounseling Referral

FINDING

• Increased risk for aneuploidy– AMA (35-singleton; 33-twins)– Positive serum screen– Abnormal ultrasound marker/finding– Family history chromosome abnormality

REASON TO CONSIDER CONSULTATION• Discuss risks to pregnancy and available testing options

– CVS– Amniocentesis– 1st or 2nd tri screening– Level II ultrasound

Aneuploidy

• Definition:– The occurrence of one or more extra or missing

chromosomes leading to an unbalanced chromosome complement, or, any chromosome number that is not an exact multiple of the haploid number

• Most common type of chromosome abnormality• Examples:

– Trisomy: one extra chromosome for a total of 47– Monosomy: one missing chromosome for a total of 45

• Typically not inherited, most trisomies occur due to nondisjunction

Case #1

• 37 y, G4P3• Referred for advanced maternal age (AMA)

and first trimester screening• Ultrasound at initial visit revealed fetus had

increased nuchal translucency (3.6 mm)• Pt declined FTS and CVS; elected to proceed

with amniocentesis after 16 weeks• Results were consistent with trisomy 21

(Down syndrome)

Case #1Trisomy 21: Down syndrome

• Most common aneuploidy, 1/800 births

• Mental retardation:– Typically mild to moderate but

encompasses full range of ability-disability

• Characteristic facial features• Hypotonia• Feeding and breathing difficulties• Congenital heart defects:

– 50% of all affected individuals– Typically AV canal defects

• Trisomy 21 is not inherited, due to nondisjunction which is a risk for each and every pregnancy at any maternal age

• Average life span 50-60

http://bagnewsnotes.typepad.com/bagnews/images/Trig1.jpg

Nuchal translucency

Normal translucency Increased nuchal translucency

Down syndrome (Trisomy 21)

http://images1.clinicaltools.com/images/gene/karyotypes/trisomy21.jpg

Case #2

• 34 y o, G1P0• Referred due to abnormal ultrasound findings:

choroid plexus cysts, clenched hands, and possible heart defect

• Findings above were confirmed also IUGR was noted• Patient was counseled on increase risk for

chromosome aneuploidy• Amniocentesis performed and karyotype revealed

trisomy 18 (Edwards syndrome)

Case #2Trisomy 18: Edwards Syndrome

• 1/3000 births• IUGR• Brain abnormalities

– Hypotonia– Seizures

• CPCs• Heart defects• Renal abnormalities• Dysmorphic features:

– Short palpebral fissures– Micrognathia – Low set ears– Clenched fists

• Cleft lip/palate• Rocker-bottom feet• Hearing loss• Feeding and breathing difficulties• High mortality rate: 90% are

miscarried or stillborn; 90% die within first year of life (most within the first few days)

http://www.ninetynineballoons.com/

Trisomy 18

Case #3

• 27 y o, G4P2• Referred for first trimester screening• Ultrasound revealed a cystic hygroma• Pt declined screening and opted for CVS• Results were 45,X or Turner syndrome

Case #345, X: Turner syndrome

• 1/2,500 births• Heart defects

– Coarctation of the aorta• Short, webbed neck• Low set ears• Swollen hands and feet• Not associated with MR but may

specific learning issues (math, etc)

• Short stature• Early loss of ovarian function• Very high miscarriage rate but if

liveborn has a very good outlook/prognosis

http://www.turnersyndrome.org

Case #3 Ultrasound Pictures

Turner syndrome (45,X)

https://images1.clinicaltools.com/images/gene/karyotypes/turnersyndromexnoy.jpg

Prenatal Testing for Aneuploidy

• In 2007, the American College of Obstetrics and Gynecology recommend that ALL women regardless of age should be counseled the risk of having a pregnancy with aneuploidy and given the option of both prenatal screening and prenatal diagnosis testing options

Modes of Prenatal Screening• Principles of Prenatal Screening:

– Uses various noninvasive tools (maternal serum, ultrasound) to provide a risk assessment for the most common trisomies

– It is not able to diagnose these conditions but determines if the patient is at either an increased or normal risk

• False positives and false negatives, cannot detect other conditions• Types

– First trimester screen• 11-14 weeks gestation• Combines maternal age, ultrasound nuchal translucency measurements, evaluation of the

nasal bone, and maternal serum levels of PAPP-A and free beta hCG• Provides an adjusted risk for trisomy 21, 18, and 13 (x:xxx chance)• Up to 91-95% detection for trisomy 21; 95% for trisomy 18 & 13• Does not screen for ONTDs; f/u with serum AFP only and/or u/s in 2nd tri

– Second trimester screen (multiple marker; AFP quad, AFP tetra)• 15-20 weeks gestation• Combines maternal age with serum levels of AFP, hCG, unconjugated estriol, and inhibin

A• Provides an adjusted risk for trisomy 21, 18, and open neural tube defects (x:xxx chance)• 75-80% detection for trisomy 21; 60% for trisomy 18, and 80-85% for ONTDs

– Integrated or Sequential Screening• Combines first & second trimester screening for ~90% detection of DS, 80% for T18

Modes of Prenatal Screening– Non-Invasive Prenatal Diagnosis

• Became available in the last year, still under study• Maternal serum screening starting at 10 weeks which evaluating cell-free

fetal DNA that circulates in maternal blood and determines the concentration of specifically tagged chromosomes

• On average, can detect:– >99% (96-100%) detection of T21 (Down syndrome)– 97%-99% (85-100%) of T18 cases– 78.6%-91.7% (50-99.9%) of T13 cases– Most labs with a <1% false positive rate

• Some labs are now including analysis for Turner syndrome & the presence of the Y chromosome

• False positives and negatives are still possible, still requires follow up prenatal dx with CVS or amnio

– Ultrasound at 18-20 weeks• Examines for markers/signs of chromosome aneuploidy; ONTDs, and

other isolated birth defects• Can be somewhat center-dependent• ~50-60% detection for trisomy 21; >90% for trisomy 18, 13 and ONTDS• Anatomy scan by OB; detailed/level II by perinate

Modes of Prenatal Diagnosis

• Chorionic villus sampling (CVS)– 10-12 weeks gestation– Chromosome/genetic/DNA analysis

performed on a sample of the chorionic villi

– 99.9% accuracy/detection of chromosome problems (genetic/DNA testing accuracy/detection is condition-specific)

– Risk of miscarriage 1/200– No analysis of AFP for ONTDs– Performed transabdominally or

transcervically

• Amniocentesis– 15-20 weeks gestation– Chromosome/genetic/DNA analysis

performed on a sample on the fetal cells found in amniotic fluid

– 99.9% accuracy/detection of chromosome problems (genetic/DNA testing accuracy/detection is condition-specific)

– Risk of miscarriage is as low as 1/1200 or 0.08%

– Provides 98-99% detection for ONTDs using analysis of amniotic fluid AFP

Tests ordered from CVS/Amnio

• Karyotype– Gold standard– Karyotype is used to

identify and evaluate the size, shape, and number of chromosomes in the fetus

– “Photograph” of the chromosomes

– Detects 99.9% of all major structural defects (trisomies, translocations, deletions)

Tests ordered from CVS/Amnio

• FISH (Fluorescent in situ hybridization)– Probes are made to “attach” to

a specific region/section of a chromosome

– Many utilizations:• Probes for common aneuploidy

(allows for rapid detection)• Probes for specific

microdeletions/microduplicatons not able to be seen on karyotype

Tests ordered from CVS/Amnio

• Chromosomal Microarray– Evaluates specific areas

(typically 100s of regions) along the human genome for gains or losses of chromosome segments at a much higher resolution than traditional karyotyping

– Typically done in cases of abnormal ultrasound findings and/or known family history of microarray abnormalities

Indications for a GeneticCounseling Referral

FINDING

• Family history genetic disease/birth defect/mental retardation

AND/OR

• Consanguinity

REASON TO CONSIDER CONSULTATION• Review pedigree, assess degree of relatedness, discuss

recurrence risks, methods of risk reductions, and discuss available testing options

The Family History inGenetics

• Fundamental component of genetic consultation• Visual record of the family

– Clarifying relationships between individual– Allows for sorting of phenotypic features relevant to

condition in question– Assists in determining the mode of inheritance if evident

• Important in establishing rapport-can learn a lot of nongenetic information from pedigree– Chief support people, social relationships, family “myths”

Putting it all together

Single Gene InheritanceAutosomal Dominant

• Examples:– Huntington Disease– Achondroplasia– Neurofibromatosis type 1 – Marfan syndrome

• Some cases in the family will be “de novo” with no previous family hx– Certain diseases are known to

have high de novo rates and there is an increased risk with h paternal age

Single Gene InheritanceAutosomal Recessive

• Cystic Fibrosis• Sickle Cell Disease• Thalassemia• PKU• Galactosemia

Increased risk with consanguinity

Single Gene InheritanceX-Linked

• Hemophilia A & B• Duchenne MD• Colorblindness• Fragile X syndrome

Multifactorial Conditions

• Examples:– Heart defects

• Maternal diabetes, ace inhibitors, lithium

– Cleft lip/Cleft palate• Cigarette smoking, folic

acid deficiency, maternal medications

– Open neural tube defects• Folic acid deficiency,

MTHFR, maternal diabetes, anti-seizure medications

Indications for a GeneticCounseling Referral

FINDING

• Preconception/prenatal genetic carrier testing

• Environmental Hazards– Maternal viral infection, teratogenic exposures

• Maternal conditions putting the fetus at risk– Diabetes, PKU

• Infertility/Recurrent pregnancy loss– Translocations; hereditary thrombophilias; patient has genetic/chromosomal

condition

REASON TO CONSIDER CONSULTATION• Discuss inheritance & testing

• Discuss risks to pregnancy & testing

• Discuss risks to pregnancy & testing

• Discuss various etiologies & offer workup as necessary

Carrier Screening• Screening the population, or particular parts of the population for their risk to have

a child with a recessive disorder• Traditionally, carrier screening was performed/offered specific to the person’s

ethnicity– Since they are recessive conditions, a normal family history does not reduce

the chances from general population risks• 1/25 Europeans are carriers of CF• 1/40 Europeans are carriers of SMA• 1/12 Africans are carriers of Sickle cell and other hemoglobinopathies• 1/9 Ashkenazi Jews are carriers of one of 9 “Jewish” conditions

• Now, with better and less expensive technology coupled with the fact that people are more often from multiple ethnic backgrounds, “Universal Genetic Carrier Screening” is utilized– Screens for over 100 autosomal recessive genetic conditions– 1/3-1/5 individuals are carriers of these conditions– Same cost as in individual disease carrier test

Aim of Counseling Regarding Prenatal Diagnosis

• Supply at risk families with information so they can make informed choices regarding pregnancy– Provide a definitive answer for condition in question which allows for:

• An accurate diagnosis to provide a prognosis, management, and recurrence risks which allows for family to either continue or end a pregnancy

• Providing reassurance to at risk families when result is normal• Allowing couples to prepare psychologically for the birth of an affected child• Helping the health care professional plan delivery, management and care of an

affected child• Providing risk information to couples to assist in making decisions regarding

their reproductive future: PGD, egg/sperm donors, adoption, natural pregnancy with diagnosis, no children

• Important points to question/inform patient– Can condition be adequately screened for/diagnosed– Will this information help them in any of the above ways such that it

outweighs the risk of the procedure?– No test can guarantee a “healthy baby”

Neonatal/Pediatric Genetics

Indications for Genetic Referral in Neonatal/Pediatric Setting

• Developmental delay or mental retardation• Dysmorphic features• Under or overgrowth• Failure to thrive• Seizure disorder of unknown cause• Hypotonia• Abnormal or ambiguous newborn screening results• Birth defect - either single or multiple• Ambiguous genitalia• Family history of genetic or chromosomal condition

Physical Examination

• Done by Medical Geneticist (MD)– Looking for dysmorphic features- subtle or distinct– Anthropomorphic measurements– Photos of other family members

• Some findings are familial---does not mean it is not a syndrome!

– Some findings are common---seen in 1-5% of the population (normal variant)

Dysmorphology Exam• Head Shape/Hair pattern• Ocular measurements• Nose• Ears• Philtrum/Mouth/Palate• Maxillary region• Mandible• Chest/Back• Limbs/Hands/Feet• GU• Skin

Common findings: seen in isolation

1-5% of population

Not so common anymore…• 6-8 Café-au-lait macules, learning disability=

Neurofibromatosis• VSD, failure to thrive, distinct nose= VCFS

Importance

• Identifies etiology• Provides prognosis and appropriate medical

management recommendations• Provides accurate risk assessment for

recurrence– Isolated cleft palate or cleft lip

• Recurrence risk based on empiric data (3-5%)

– If syndromic, recurrence risk may be up to 50%. • 22q11.2 deletion (DiGeorge syndrome), Van der Woude,

Stickler syndrome

Other tools….

• Karyotype• FISH for specific suspected syndrome• Gene specific testing for suspected syndrome• Chromosomal microarray

– Is now considered by many societies as a first-tier clinical diagnostic test for individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA)

Newborn Screening –More Than

“The PKU Test”!• CYSTIC FIBROSIS• ENDOCRINE CONDITIONS: Congenital adrenal hyperplasia

(CAH)*± • Congenital hypothyroidism*• HEMOGLOBIN CONDITIONS:Sickle cell disease and other

hemoglobinopathies*• METABOLIC CONDITIONS:

– AMINO ACID CONDITIONS : Homocystinuria* • Hyperphenylalanemia, including • phenylketonuria (Pk ) Tyrosinemia*

– FATT y ACID OxIDATION CONDITIONS : Carnitine uptake defect • Carnitine palmitoyl transferase I deficiency (CPT I)* • Carnitine palmitoyl transferase II deficiency (CPT II) • Multiple acyl-CoA dehydrogenase deficiency • (MADD) Short chain acyl-CoA dehydrogenase deficiency • (SCAD) Medium chain acyl-CoA dehydrogenase deficiency • (MCAD)± Long chain 3 hydroxyacyl-CoA dehydrogenase • deficiency (LCHAD)*± Very long chain acyl-CoA dehydrogenase • deficiency (VLCAD)*±

– ORgANIC ACID CONDITIONS : Beta-ketothiolase deficiency • (BkD)± Glutaric acidemia, Type I (GA I)* • Isobutyryl CoA dehydrogenase deficiency • (IBD)± Isovaleric acidemia • (IVA)* ± Malonic aciduria • Maple syrup urine disease • (MSuD)± Methylmalonic acidemias (MMA/8 types)± • Propionic acidemia • (PA)*± 3-Hydroxy-3-methylglutaryl CoA lyase • deficiency (HMG)* 2-Methyl-3-hydroxybutyryl CoA dehydrogenase • deficiency (MBHD)* 2-Methylbutyryl CoA dehydrogenase • deficiency (2MBC)* 3-Methylcrotonyl CoA carboxylase deficiency (3MCC) • 3-Methylglutaconyl CoA hydratase deficiency (3MGH) • Multiple carboxylase deficiency

– UREA CyCLE CONDITIONS : Arginase deficiency • Argininosuccinate lyase deficiency (ASA)± • Citrullinemia±

– OTHER CONDITIONS : Biotinidase deficiency • Galactosemia±

Newborn Hearing Screening

1/1000 young children have a major hearing loss

50% of congenital hearing loss is genetic

• Early diagnosis is key to proper management

Pregnancy & Neonatal Loss

Chromosome Abnormalities in Pregnancy Loss

• Approximately 25% of all clinically recognized pregnancies result in a loss• <20 weeks = miscarriage

– Up to 50% are due to chromosome aneuploidy• Most are due to nondisjunction with little increased risk of

recurrence• However, karyotyping can be indicated in repeat pregnancy loss

since 2-5% of couples have a chromosomal abnormality causing the increased RR

• >20 weeks = stillbirth– 5% are due to chromosome abnormalities– However, some of these do increase the RR and when no other cause is

known it is recommended to consider karyotype and/or microarray

Importance of a Genetic Workup

• Can allow for a diagnosis which will answer some of the most important questions a parent will have– Why?– Will this happen again?– Was it my fault?

• Therefore workups and often autopsies are essential

Grief and Bereavement

• Pregnancy loss is the same to the majority of parents, if not worse, than any other type of death

• It is extremely important to encourage, respect, and promote proper grieving of a loss no matter how early– It’s often a loss of dreams/hopes/expectations– Avoid comments that take away from the current situation: you can

have another one, at least it was early, etc• Important to:

– See, hold, spend time with the baby/body– Take photos, they can always be kept in patient chart if not ready to

take them home– Name the baby, memorialize the baby in some meaningful way to the

family– Encourage the family to recognize their spiritual or religious beliefs– Discuss cremation/burial options

• Offering gentle and beautiful photography services in a compassionate and sensitive manner

• Work done by professional photographers who volunteer their services and are trained in this specific area– Photographers will work with

families in order to fit their needs and desires

• Soft, gentle heirloom photographs of these beautiful babies are an important part of the healing process

• They allow families to honor and cherish their babies, and share the spirits of their lives

• www.nowilaymedowntosleep.org

Perinatal Hospice“When the prenatal diagnosis of a lethal fetal anomaly has

been established, some patients choose to continue their pregnancies. We propose a model of care that incorporates the strengths of prenatal diagnosis, perinatal grief management, and hospice care to address the needs of these families.”

—Hoeldtke NJ, Calhoun BC. "Perinatal Hospice." Am J Obstet Gynecol. 2001 Sept;185(3)525-9

• Medical, emotional, and spiritual support through pregnancy, labor, birth, life and death

• Variety of services to help parents define a birth vision they are comfortable with

• Families may choose any of the services that fit their needs

“Regardless of the length of a baby's life or duration of illness, it is their lifetime. Both the infant and family deserve skilled and compassionate attention to their plight; a safety net throughout the experience; a palliative care approach, which emphasizes living fully those days, hours, and even moments.”

—Sumner LH. Taking palliative care into pregnancy and perinatal loss. National Perinatal Association Bulletin. 2004;5(2).

A news clip on Now I Lay Me Down To Sleep.

http://www.msnbc.msn.com/id/21134540/vp/23481435#23481435

Thank You

Questions?