Congenital infections & disorders Flashcards
Aneuploid
- Cells deviating from
the multiple of the
haploid number - 23 paired chromosomes
(+) or (−) preceding the
chromosome number
indicates _____
↑ or ↓ whole chromosome in a cell
47, XY+21
Designates a ♂ with 3
copies of chromosome 21
(+) or (−) after the chromosome
number signifies _____
extra or missing material on 1 of the arms of the
chromosome
46, XX, 8q−
Denotes a deletion on the
long arm of chromosome 8
Trisomy: ____
3 of a particular chromosome
Monosomy: _____
Only 1 of a particular chromosome
Examples of structural
chromosomal abnormalities:
- Deletion
- Duplication
- Inversion
- Ring chromosome
- Translocation
- Insertion
Xenobiotics
compounds foreign to nature
Neural Tube Defects
Anencephaly, encephalocele, spina bifida (myelomeningocele), sacral agenesis, & other spinal dysraphisms
Etiology of Neural Tube Defects
- Neural tube develops via closure at multiple closure sites
– Each is mediated & affected by different genes & teratogens
– Usual cause → Folate Deficiency - Combined with genetic &/or environmental factors
Neural Tube Defects Presentation
- Lesions at birth
– Extent of neurologic deficit depends on the lesion level (Open vs. subtle skin covering)
Diagnosis of neural tube defects and importance of early diagnosis
- Prenatal screening
– Ultrasound
– Maternal alpha-fetoprotein (AFP) - Specific globulin from the yolk sac, GI tract, & liver
- In maternal serum, amniotic fluid, & fetal plasma
– AFP Concentration: Maternal serum AFP < Amniotic fluid or Fetal plasma
Ultrasound Screening (US) guidelines for neural tube defects
- Transabdominal → 18-20 weeks
– Detection rate = 92-100% for NTD - Transvaginal → 12-14 weeks
– Detection rates vary
44% (spina bifida) >90 (anencephaly)
Management of Myelomeningocele (Spina Bifida)
– Possible fetal surgery to stop
leakage of spinal fluid & possibly
prevent hindbrain herniation & hydrocephalus
– Delivery
* No benefit of pre-labor cesarean delivery
* Meningocele is unlikely to cause dystocia
Management of anencephaly
- Poor prognosis
– Most are stillborn or die shortly after birth - Most pregnancies are terminated or induced
- These infants are poor candidates for organ donation
Management of Encephalocele
- No data available
- Vaginal delivery may be safe (small lesion)
– Cesarean delivery (large lesions)
Complications of Myelomeningocele
- Poor prognosis
- Intellectual disability
- Hydrocephalus
- Clubfeet
- Dislocated hips
- Neurogenic bowel & bladder
- Total flaccid paralysis
– Below lesion level
Complications of Encephalocele
- Poor prognosis
- Intellectual disability
Most common craniofacial malformation of the newborn
Cleft Palate
Etiology of cleft palate
- Genetic ~10% have a genetic variant
- Environment (drugs)
- Folate deficiency
1. Maternal smoking
2. Maternal obesity
3. Syndromes
Nursing education for cleft palate
- Difficult* for most infants to generate negative intraoral pressure to suck milk effectively from bottle or breast
- Often can be bottle fed with formula or expressed breast milk with adaptive
feeding equipment
*Some infants may be able to breast feed & the
soft breast tissue will fill gaps & create suction
Management of cleft palate
- When Dx’d prenatally, recommend amniocentesis
- High % of chromosomal abnormalities for this population
- Surgical Repair
– Primary lip repair at 3 months
– Palate repair ~6 months
Phenylketonuria (PKU)
PKU is a d/o affecting the amino acid phenylalanine
* Infants lack phenylalanine hydroxylase (PAH)
* Causes Intellectual disability
Etiology of PKU
- Most cases of PKU are caused
by Phenylalanine hydroxylase
deficiency
– Autosomal recessive inheritance - ↑ serum phenylalanine: Disrupts brain growth,
myelination & neurotransmitter synthesis
Phenylketonuria (PKU) S&S
– Seizures
– Microcephaly
– Behavioral abnormalities
– Irreversible intellectual disability
– Insidious onset (Signs & symptoms begin
after initiating feeds with breast milk or standard
formula)
PKU diagnosis
- Newborn Screening
– Mass spectrometry
– ↑ phenylalanine concentration
– ↓ tyrosine concentration - ↑ serum & urine concentration of phenylalanine
PKU management
- Restrict dietary phenylalanine
- Consume phenylalanine-free protein substitutes
- Breastfeeding is encouraged under the
supervision of an experienced metabolic
dietitian & is alternated with phenylalanine-free formula feeding
– Breast milk (↓ phenylalanine concentration)
Galactosemia
↑ serum galactose concentration 2° deficiency ≥ 1
* Galactose-1-phosphate uridyl transferase (GALT)
– MOST common & severe
* Galactokinase (GALK)
* Uridine diphosphate galactose 4-epimerase
Galactosemia etiology
- Autosomal-recessive disorder
Galactosemia presentation
- Jaundice -74% *
- Vomiting - 47% *
- Hepatomegaly - 43% *
- Failure to thrive – 29%
- Poor feeding -23%
Diagnosis of galactosemia
Done with newborn screening
* Serum/Blood
* Urine
(review specifics in slides)
Galactosemia management
(+) screening test = change immediately to a soy-based infant formula (no galactose)
– Repeat screening test
– Minimize dietary galactose
Hemoglobinopathies
A group of inherited disorders causing abnormal
production or structure of the hemoglobin molecule
Hemoglobinopathies includes
- Hemoglobin C disease
- Hemoglobin S-C disease
- Sickle cell anemia
- Thalassemias
Most common chromosome abnormality in liveborn infants
Trisomy 21 (Down Syndrome)
Most common cause of intellectual disability
Trisomy 21 (Down Syndrome)
Trisomy 21 (Down Syndrome) - 3 cytogenic variants
- 3 full copies of chromosome 21 – 94% of patients
- Translocation → 3 copies of the critical region for Down syndrome
- Mosaicism
Features of Neonates with Trisomy 21 (Down Syndrome)
- Hypotonia
- ↓Moro reflex
- Anomalous ears
- Slanted palpebral fissures
- Dysplasia of mid-phalanx
- Flat facial profile
- Transverse palmar crease
- Excessive nape skin
- Hyperflexibility of joints
- Dysplasia of pelvis
Clinical Presentation of Trisomy 21 (Down Syndrome)
- Intellectual disability (IQ → 20-75)
- Congenital cardiac defects (~50%)
- Language delays in childhood
- Atlantoaxial hypermobility
- Characteristic facies
- Hand anomalies
- ↓ Height for age
- 18-38% Psychiatric d/o
- Impaired immune response
- ↓ Thyroid function
- Intestinal malabsorption
- ↑ insulin resistance & DM
- Premature senescence
- Leukemia predisposition
Trisomy 18 (Edwards Syndrome)
- Trisomy 18 (47,+18)
– 90% result form meiotic nondisjunction (Associated with advanced maternal age) - Translocation → chromosome 18
- Trisomy 18 mosaicism (47,+18/46)
2nd most common autosomal
trisomy observed in live births
– Most die prenatally
– 50% die within 2 weeks
Trisomy 18 (Edwards Syndrome) clinical presentation
- Intrauterine growth restriction
- Congenital heart disease >50%
- Hypertonia
- Prominent occiput
- Small mouth
- Micrognathia
- Pointy ears
- Horseshoe kidney
- Flexed fingers
- Overlapping fingers
- GI system involvement ~75%
- Meckel diverticulum & malrotation
- Omphalocele
- Severe Intellectual disability
- Short sternum
Trisomy 13 (Patau Syndrome) - two types
- Trisomy 13
(47,+13)
* meiotic error
* Advanced maternal age
* ~98.5% embryonic death - Trisomy 13 mosaicism
(47,+13/46)
* Mitotic nondisjunction error
* 3 copies of chromosome 13 in
some cells & 2 in others
* NOT related to maternal age
Trisomy 13 (Patau Syndrome) clinical presentation
- Micro/anophthalmia
- Left lip &/or palate,
- Postaxial polydactyly
- Other common features: Incomplete development of forebrain & olfactory &
optic nerves, severe intellectual disability,
deafness
~80% of patients may have with Trisomy 13 (Patau Syndrome) have
- Ventricular Septal Defect
- Patent Ductus Arteriosus
- Atrial Septal Defect
- Dextroposition
Most common sex chromosome abnormality in females
Turner Syndrome
Turner Syndrome presentation
- Most Common → Short stature
– ~50%, cardiac malformation
– Short & webbed neck
– Nonverbal learning d/o
– Primary ovarian failure
– Hypothyroidism
– Hearing loss
– Scoliosis
– “Shield chest”
Marfan Syndrome
Connective tissue disease
– Autosomal dominant
– genetic mutation
* Chromosome 15, FBN1 gene
– Leads to connective tissue weakness
– Pleiotropic effects
Marfan Syndrome characteristics
- Tall, thin stature
- Arm span longer than height
- Body ratio < 0.85 (nl 0.89-0.95)
- Back pain
- Vision problems
- Cardiovascular problems
- Spontaneous pneumothorax
Klinefelter Syndrome characteristics
Males
* ↑ lower/upper body segment ratio
* Gynecomastia
* Small penis
* Sparse body hair
* ♀pubic hair pattern
Primary Hypogonadism features in Klinefelter Syndrome
- Gynecomastia
- Infertility
- Mild cognitive
impairment possible - “Eunuchoid habitus”
What does “Eunuchoid habitus” mean with klinefelter syndrome?
- Tall, slim & underweight
- Long legs & arms
I.e., arm span exceeds height by 5+ cm
Fragile X Syndrome
A genetic disorder characterized by intellectual disability & other neurodevelopmental disorders
(Esp. ADHD & Autism Spectrum Disorder)
Fragile X Syndrome etiology
- Caused by loss-of-function mutation on fragile X mental retardation 1 gene (FMR1)
– located on long arm of X chromosome - X-linked dominant inheritance
Fragile X Syndrome clinical presentation
- Developmental delay
– Speech delay (esp. boys - Motor delay
- Behavioral concerns
- Cognitive deficits
- May have connective tissue dysplasia
- Mitral valve prolapse *
Four major groups of teratogens
- Intrauterine infections: T.O.R.C.H. infxs
- Medications & drugs
- Physical causes
- Maternal metabolic diseases
TORCH
Toxoplasmosis
Other agents (congenital syphillis, zika, etc.)
Rubella
CMV
Herpes simplex
Tetrad of findings in rubella
- Cataracts
- Heart defects
* PDA & Pulmonary stenosis - Deafness
- Intellectual Disability
“Blueberry muffin purpura” is seen in
Rubella
Cytomegalovirus (CMV) signs
- Intrauterine growth retardation
- Hepatosplenomegaly
- Hemolytic anemia
- Encephalitis
- Microcephaly
Antiviral agent of choice for neonatal
herpes simplex virus infections
Acyclovir
Alcohol is an _____ CNS teratogen
IRREVERSIBLE
Risk factors for Fetal Alcohol Syndrome
– Sibling with FAS
– Lived in an orphanage or been placed in foster care
– In psychiatric care
– Hx with CPS or the juvenile justice system
3 characteristic facial features of Fetal Alcohol Syndrome
- Short palpebral fissures
- Thin vermillion border
- Smooth philtrum
Fetal Alcohol Syndrome management
- Early identification & intervention
- Behavioral therapy
– Individual & family
– Parent training
Fetal Hydantoin Syndrome
a characteristic pattern of mental and physical birth defects that results from maternal use of the anti-seizure (anticonvulsant) drug phenytoin (Dilantin) during pregnancy
Fetal hydantoin syndrome facial features
- Upturned nose
- Mild midfacial hypoplasia
- Long upper lip with thin vermilion border
Other:
B. Distal digital hypoplasia
ACE-Inhibitor Fetopathy
ACE-inhibitors cause fetal hypotension
Issue with Taking NSAIDS late in pregnancy
- Inhibit prostaglandin synthesis
- Taken late in pregnancy → ductus arteriosus closure & causes pulmonary hypertension
Avoid NSAID use in pregnancy!
Ionizing Radiation effect as a teratogen
– Tissue reaction to radiation are related to the dose
– The severity of the reaction ↑ as the dose ↑
– Adverse outcomes include:
– Abortion
– Growth restriction
– Congenital malformations
— Microcephaly
— Intellectual disability
Maternal metabolic diseases (Diabetes Mellitus) can cause these things in newborns
- Anencephaly
- Encephalocele
- Meningomyelocele
- Spina bifida
- Holoprosencephaly
- Transposition of the great vessels
- Cardiac defects (many)
