clinical vignettes Flashcards
cause of down syndrome
- trisomy 21 (95%)
- unbalanced translocation between 21 and another afrocentric chrome (3-4%)
- mosaic tri 21 (1-2%)
Trisomy 21 is unbalanced translocation between
chromosome 21 and another afrocentric chromosome
important to check karyotype of parents
trisomy 21, 95% of patients with
down syndrome
parents usually have normal chromosomes
recurrence risk is 1:100
mosaic trisomy is
mixture of norma cells and cells containing trisomy 21
1-2% of down syndrome
phenotype tends to be more mild
approach to prenatal counseling in DS
- caused by error of nondysjunction
- increasing risk with increasing maternal age
- prenatal screening
DS first trimester screening:
detects 82-87%
ultrasound measurement of nuchal fold +B-hCH (human chorionic gonadotropin) + PAPP-A (pregnancy-associated plasma protein A)
DS second semester screeing:
-detection rate 80%
-quad screen-hCG (human chorionic gonadotropin), AFP (α-fetoprotein), unconjugated estriol, and inhibin level
– Suspicion of DS based on 1st or second trimester screening can by confirmed by chromosome analysis via amniocentesis or CVS (chorionic villus sampling)
– Detection rate of 1st trimester + second trimester screening =
95%
increased risk of trisomy with
advanced maternal age
PW Presentation in newborn period
hypotonia and
dysmorphic features, undescended testicles.
PW diagnosis made by
Diagnosis can be made with FISH or microarray
marker on chromosome 15, SNRPM deletion
PW symptoms:
-early failure to thrice and feeding difficulties
-preschool age hyperphagia and weight gain
-ophthalmologic problems
strabismus and nystagmus
PW treatment
growth hormone to help control obesity and improve short stature
Deletion on Paternal chromosome 15 results in
prader willi
deletion on maternal chrom 15 results in
angelman’s syndrome
Prader-Willi Syndrome results when genetic information is missing from ______
the paternal allele of 15q11-q13.
This region of chrm 15 is imprinted
PWS can be caused from
deletion of paternal allele or
uniparental disomy of the maternal allele
PWS testing:
The maternal and paternal alleles are marked by different patterns of methylation. Therefore, methylation testing of this chromosome is one way to diagnose PWS or Angelman syndrome. If a deletion is present, a FISH test or a miccroarray can be done to confirm the diagnosis.
PWS infancy:
- hypotonic
- almond shaped eyes
- undescended testicles
- severe feeding problems which often necessitate placement of a feeding (Gtube) gastrostomy tube. 5. lighter pigmentation
Toddler/Preschooler:
- feeding problems completely reverse, and the child will eat anything and everything, without ever feeling sated.
- very obese, unless treated with growth hormone.
PWS: Common Medical Issues:
- Eyes: strabismus, nystagmus common
- Orthopedics: scoliosis is common
- Respiratory: obstructive sleep apnea
- Developmentally: mild-moderate cognitive disabilities, behavioral issues
Linkage disequilibrium between patients with Autism and polymorphisms in the _________ have been reported. _________ is an important neurotransmitter in the CNS.
GABAA –b3 locus on chromosome 15q
γ-aminobutyric acid type-A
_________
chromosome anomalies are one of the most frequently reported cytogenetic
abnormalities in patients with autism
Maternally derived proximal 15q11-q13
15q interstitial duplication
A piece of a chromosome can be copied, resulting
in a duplication or partial Trisomy (in this picture,
the duplication is an
interstitial duplication
in the middle of the chromosome
Angelman Syndrome etiology:
5q deletion in PWS/AS region from maternal allele, detected with FISH, UPD of 15q, or imprinting errors of 15q detected with methylation studies
angelman syndrom symptoms
mildly dysmorphic facial features, hypotonia in infancy
spasticity in older patients, Intellectual Disability (ID), seizures,
autism
Chrom abnormalities in 15 cause:
- PWS: paternal deletion
- Angelman syndrome: maternal deletion
- IDIC 15: associated with autism/hypotonia/seizures/ID
- Maternally inherited interstitial duplication: associated with autism/hypotonia/seizures/ID
Causes of down syndrome
- Trisomy 21: 95%
- Unbalanced Translocation between chromosome 21 and another acrocentric chromosome: 3-4%
- Mosaic Tri 21(mixture of normal cells and cells containing Tri 21): 1-2 %
3 kinds of trisomy associated with live births
13, 18, 21
infants with DS
– Growth parameters normal – midfacial hypoplasia – upslanting palpebral fissures – small ears – large-appearing tongue – low muscle tone, -- increased joint mobility – short fingers, --transverse palmar crease*, Vth finger incurving (clinodactyly), increased space between toes 1 and 2
DS common medical issues
- cardiac issues
- Gastrointestinal
- Ophthalmologic
- Ear, Nose, Throat Problems
- Endocrine problems
- Orthopedic problems
- Hematologic issues
- developmental
- Neurologic
- Psychiatric
DS Cardiac issues
– Seen in approximately 50% of patients with DS
– All types of anomalies may be present, but Atrioventricular Canal is common to DS
– Echocardiogram in the newborn period is recommended
DS Gastrointestinal
– 10-15% of infants have structural anomalies 1. Esophageal atresia 2. Duodenal atresia 3. Hirschsprung’s – functional GI issues 1. Feeding problems 2. constipation 3. GERD 4. Celiac Dz
DS Ophthalmologic problems
- blocked tear ducts
- myopia
- lazy eye
- Nystagmus
- Cataracts
DS– Ear, Nose and Throat
- chronic ear infections
- Deafness – both sensorineural and conductive – chronic nasal congestion
- enlarged tonsils and adenoids
- obstructive apnea
DS: Endocrine Problems
- Thyroid dz – most commonly hypothyroidism
- Insulin Dependent Diabetes – Alopecia Areata
- reduced fertility (but normal puberty)
DS: Orthopedic Problems
- hips
- Joint subluxation
- atlantoaxial subluxation
DS Hematologic problems
- Myeloproliferative disorder in newborn
- increased risk of leukemia 12-20x
- iron deficiency anemia
DS developmental problems
Psychiatric problems
Depression
Early Alzheimer’s
Autism= 1/10
Turner syndrome karyotype
XO
Turner’s syndrom CVS abnormailites
- bicuspid aortic valve
- Coarctation of aorta
- systemic hypertension
- prolonged QTc syndrome
- Partial anomalous pulmonary venous connection
- Persistent left SVC
Turner’s syndrome eye abnormalities
- inner canthal folds
- ptosis
- blue sclera
Turner syndrom skeletal abnormalities
- cubitus valgus
- short 4th metacarpal
- short stature
Turner syndrom neck
- webbed neck
- low hairline
- cystic hygroma
Turner syndrome learning abnormalities
- difficult in math
- visual spatial skills
- low non verbal scores
effective health outcome =
patients culture +physicians culture
Turner’s syndrome: challenges across lifespan
- infertility
- stature
- sexual development
- concerns regarding health and aging
Turner’s syndrome: common pitfalls in disclosure
- secret keeping
- difficulty communicating an infertility diagnosis
- perceived negative experiences with physicians
