Genetics Flashcards
why do we do a karyotype for Down syndrome
important to tell the recurrence risk to parents
if it is due to a unbalanced translocation then one of the parents may be a carrier of a balanced translocation
what is the risk of Down syndrome in any 40 year old woman?
1%
what is the risk of Down syndrome if the mother is a carrier of a balanced translocation
~15%
less if father is the translocation carrier
what are some physical features in a neonate of Down Syndrome
Hypotonia * Poor Moro reflex * Flat face * Upward slanted palpebral fissures * Epicanthal folds Speckled irises (Brushfield spots) Small nose, flat nasal bridge Small dysplastic ears * Joint hyperflexibility * Short neck, redundant skin * Short metacarpals and phalanges Short 5th digit with clinodactyly * Single transverse palmar creases *- impt Wide gap between 1st and 2nd toes- impt Pelvic dysplasia * GI: duodenal atresia and hirschsprung disease- impt
what are the congenital heart defects associated with Down Syndrome
congenital heart defects (50%) atrioventricular septal defects ventricular septal defects isolated secundum atrial septal defects patent ductus arteriosus tetralogy of Fallot
what are brushfield spots? are they pathognomonic for Down syndrome?
Brushfield spots are speckled areas that occur in the periphery of the iris
No! They are seen in about 75% of patients with Down syndrome, but they also are found in up to 7% of normal newborns.
what are some physical exam findings suggestive of Trisomy 18
IUGR microcephaly rockerbottom feet Clenched hands with overlapping fingers Dolichocephaly(condition where the head is longer than would be expected with a prominent occiput) Dysplastic or malformed ears short sternum Shield chest with wide set nipples
what are some physical exam findings suggestive of Trisomy 13
cutis aplasia
holoprosencephaly
midline defects (cleft lip and palate)
post-axial polydactyly (extra digits on the ulnar side of the hand)
hypertelorism
birth weight usually in the normal range (unlike trisomy 18)
what is more of the most common causes of holoprosencephaly
trisomy 13
what is the gold standard test to diagnose Trisomy 13
karyotype
if you need a rapid diagnosis you can do FISH
Family physician calls you about term neonate who weighs 2300 g. Neonate has lymphoedema, low set hair line and wide chest.
1) What test would you send for diagnosis?
Karyotype
what are some physical exam findings suggestive of Turner syndrome
Short stature
Congenital lymphedema
Horseshoe kidneys
Patella dislocation
Increased carrying angle of elbow (cubitus valgus)
Madelung deformity (chondrodysplasia of distal radial epiphysis)
Congenital hip dislocation
Scoliosis
Widespread nipples
Shield chest
Redundant nuchal skin (in utero cystic hygroma)
Low posterior hairline
Coarctation of aorta
Bicuspid aortic valve
Cardiac conduction abnormalities
Hypoplastic left heart syndrome and other left-sided heart abnormalities
Gonadal dysgenesis (infertility, primary amenorrhea)
Gonadoblastoma (increased risk if Y chromosome material is present)
Learning disabilities (nonverbal perceptual motor and visuospatial skills) (in 70%)
Developmental delay (in 10%)
Social awkwardness
Hypothyroidism (acquired in 15–30%)
Type 2 diabetes mellitus (insulin resistance)
Strabismus
Cataracts
Red-green color blindness (as in males)
Recurrent otitis media
Sensorineural hearing loss
Inflammatory bowel disease
Celiac disease (increased incidence)
what are two investigations that should be completed for a patient with Turner syndrome
Congenital heart defects (40%) and structural renal anomalies (60%) are common.
cardiac evaluation for bicuspid aortic valve, coarctation of the aorta, valvular aortic stenosis, and mitral valve prolapse.
renal ultrasound to look for renal anomalies such as horseshoe kidney
physical exam findings of turners syndrome in a newborn
small size for gestational age
webbing of the neck
protruding ears
lymphedema of the hands and feet
what are the most common heart defects seen with turners syndrome
The most common heart defects are bicuspid aortic valves, coarctation of the aorta, aortic stenosis, and mitral valve prolapse.
what are some physical exam findings suggestive of Noonan syndrome
short stature low posterior hairline shield chest congenital heart disease: Pulmonary stenosis and hypertrophic cardiomyopathy are generally the most common congenital heart defects found in Noonan syndrome short or webbed neck
what testing should be done for Noonan syndrome
molecular testing or gene sequencing (not seen on microarray)
floppy baby suggest what genetic syndrome
Prader Willi
child with seizures suggests what genetic syndrome
TS
Angelman syndrome
child with regression suggests what genetic syndrome
Rett syndrome
child with autism and intellectual disability suggests what 3 genetic syndromes
Fragile X
22q11 deletion syndrome
NF1
what are some neonatal findings of PWS
hypotonia- hyporeflexia, weak cry, lethargy
feeding difficulties- poor suck, FTT
hypogonadism- cryptorchidism, small testes and scrotum
what are features of prader-willi syndrome
voracious appetite
obesity in infancy
short stature (responsive to growth hormone)
small hands and feet
hypogonadism
intellectual disability (40% have borderline to low average IQ)
behaviour- often challenging due to hyperphagia, compulsivity, resistance to change and OCD tendencies
what causes prader will syndrome
paternal deletion
15q11-q13
what is the genetic test for prader willi syndrome
cytogenetics
MS-MLPA
what causes Angelman syndrome
ALL MAN- don’t have woman’s copy
maternal deletion
15q11-q13
reciprocal of Prader willi syndrome
what are the main clinical features of Angelman syndrome
developmental delay- notable around 6 months of age
severe speech impairment *
acquired microcephaly
gait ataxia and/or tremulousness of the limbs
behaviour: happy demeanour, frequent laughing, smiling, hypermotoric and excitability
microcephaly
seizures
what are common presentations of 22q11.2 (DiGeorge) deletion syndrome
CATCH
Cardiac abnormality (commonly interrupted aortic arch, truncus arteriosus and tetralogy of Fallot) *conotruncal malformations Abnormal facies (squared nasal root) Thymic aplasia Cleft palate and submucosal cleft palate Hypocalcemia/hypoparathyroidism
A child with supravalvular aortic stenosis, small and abnormally shaped primary teeth, low muscle tone with joint laxity, and elevated calcium noted on testing is likely to have what syndrome?
Williams syndrome
what causes William syndrome
microdeletion on chromosome 7
what are associated anomalies with William syndrome
Associated anomalies:
congenital heart defects (~80%)- supravalvular aortic stenosis **
inguinal or umbilical hernias
Hypercalcemia **
feeding difficulties hypertension hypothyroidism developmental delay anxiety*
what is the single best test for 22q11.2 deletion syndrome
FISH or MLPA
also picked up on microarray
if hemivertebrae what workup should you consider?
workup for VACTERL
VACTERL is a diagnosis of exclusion
genetic basis unknown usually sporadic
expect normal intellect
what is Alagille syndrome
Autosomal dominant
complex multi system disorder characterized by the presence of 3/5 major clinical criteria:
- cholestasis with bile duct paucity on liver biopsy
- congenital cardiac defects
- posterior embryotoxon in the eye
- characteristic facial features (broad forehead; deep-set, widely spaced eyes; long, straight nose; and an underdeveloped mandible)
- butterfly vertebrae
what is the triad of Beckwith-Wiedemann syndrome
OMG
O- ompahocele
M- macroglossia
G- gigantism (hemihypertrophy)
what does VACTERL mean
Vertebral defects Anal atresia Cardiac malformations Tracheoesophageal fistula Renal dysplasia Limb abnormalities
usually at least 1 anorectal or TEF, hemivertebrae can be seen in VACTERL
Newborn with respiratory distress and you are unable to pass an NG through nares. Child with distress, cannot pass NG through nares.
what syndrome?
3 other things you would look for on physical exam?
CHARGE Coloboma Heart defects choanal Atresia Retarded growth and development Genital abnormalities Ear anomalies
what are the major physical exam findings for BWS
Macrosomia (traditionally defined as weight and length/height >97th centile)
Macroglossia
Hemihyperplasia (asymmetric overgrowth of one or more regions of the body)
Omphalocele (also called exomphalos) or umbilical hernia
Embryonal tumor (e.g.,Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma) in childhood
Visceromegaly involving one or more intra-abdominal organs including liver, spleen, kidneys, adrenal glands, and/or pancreas
Cytomegaly of the fetal adrenal cortex (pathognomonic)
Renal abnormalities including structural abnormalities, nephromegaly, nephrocalcinosis, and/or later development of medullary sponge kidney
Anterior linear ear lobe creases and/or posterior helical ear pits
Children with Beckwith-Wiedemann syndrome are at increased risk of which childhood cancers?
Wilm’s tumor- is the most common
95% of Wilms’ tumors occur by age 7.
Hepatoblastoma- is the second-most common cancer in patients with Beckwith-Wiedemann syndrome.
Typically develops by age 2.
what screening is required for BWS
Screen for embryonal tumors by abdominal ultrasound examination every three months until age eight years
Monitor serum alpha-fetoprotein (AFP) concentration every two to three months in the first four years of life for early detection of hepatoblastoma.
Annual renal ultrasound examination between age eight years and mid-adolescence to identify those with nephrocalcinosis or medullary sponge kidney disease
how do patients with achondroplasia present?
typically manifest at birth with short limbs, a long narrow trunk, and a large head with midfacial hypoplasia and prominent forehead.
The limb shortening is greatest in the proximal segments, and the fingers often display a trident configuration
dominant condition
due to 1 or 2 specific gene changes in a specific gene (FGR3 mutation)
TS major criteria
At least 2 major or 1 major and 2 minor A La Grass Hut A- facial angiofibromas ≥ 3 or forehead plaque L- lymphangiomyomatosis A- Ash leaf spots (hypo pigmented macules ≥ 3, >5mm in diameter) G- giant cell subependymal astrocytoma R- rhabdomyoma in heart A- angiomyolipoma of the kidney S- shagreen patch S- subependymal nodules H- hemaratomas of the retina U- ungal fibromas ≥ 2 T- tubers
periventricular calcification- can change into giant cell astrocytoma
what is the inheritance pattern of TS and NF1
Autosomal dominant
how is TS diagnosed
molecular testing
NOT microarray or cytogenetics
what are 3 common brain imaging findings in TS
subependymal nodules (90%) cortical tubers (70%) SEGAs- subependymal giant cell asytrocytoma (5-15%0
rett syndrome presentation
x linked
females only
Development may proceed normally until 1 yr of age, when regression of language and motor milestones and acquired microcephaly become apparent. An ataxic gait or fine tremor of hand movements is an early neurologic finding.
The hallmark of Rett syndrome is repetitive hand-wringing movements and a loss of purposeful and spontaneous use of the hands; these features may not appear until 2-3 yr of age. Autistic behaviour is a typical finding in all patients.
Generalized tonic-clonic convulsions (up to 90%) occur in the majority but may be well controlled by anticonvulsants.
what gene is associated with Rett syndrome
MECP2
what is the classical presentation for Fragile x syndrome
male with moderate intellectual disability or a female with mild intellectual disability macrocephaly long face protuberant ears post pubertal macroorchidism* joint laxity flat feet MVP seizures- complex partial most common
how is fragile x diagnosed
DNA testing or molecular testing
CGG repeats in FMR1 gene on x chromosome
what clinical features are associated with a female who has a permutation for fragile x
premature ovarian failure, early menopause
Fragile X-associated tremor/ataxia syndrome (FXTAS)
learning problems
chance to have more children with fragile x syndrome
NF1 criteria
CROPLAND
Marfan is similar to what metabolic condition
homocystinuria
How can you distinguish Marfan from homocystinuria
Marfan- have cardiac manifestations (aortic dilatation) whereas homocytinuria patients present with learning issues and have increased risk of thromboembolism
Homocytinuria- autosomal recessive
Marfan- autosomal dominant
how is Duchenne muscular dystrophy diagnosed
molecular testing of dystrophin gene
what is a good screening test for Duchenne muscular dystophy
CK
if you see a female with classic features of Duchenne muscular dystrophy what does she likely have?
Turner syndrome
what are the physical exam findings associated with Marfan syndrome
MISS TINA RAPED at 15:00
15:00= 15 chromosome
m=mitral valve prolapse/myopia
i=inguinal and incisional hernia
s=spontaneous pneumothorax
s=striae,scoliosis/kyphosis
tina= tall i.e.long bones
r=retinal detachment a=arachnodactyly/aortic regurgitation p=pectus excavatum, rectus carinatum e=ectopia lentis d dislocation of lens
how is Marfan syndrome diagnosed?
molecular testing (not microarray or cytogenetics) Fibrillin 1 gene analysis
what is seen on pedigree for autosomal dominant (3)
affected individuals in every generation
male to male transmission
males and females equally affected
what is seen on pedigree for autosomal recessive condition
some offspring affected and some not
consanguinity (increases risk of autosomal recessive condition)
may see skipped generation
what is seen on pedigree for x linked inheritance
NO male to male transmission
males > females
features of mitochondrial transmission
mitochondria is inherited from our mother
if a male has it then no children will have it
if a female has it then all of the children will have it
what is primary prevention and what are some examples of primary prevention
to stop inherited and non-inherited disorders from arising in the first place by identifying and avoiding causative factors
ex: folic acid to prevent NTD
carrier screening for couples from certain ethnic backgrounds for autosomal recessive conditions (Ashkenazi Jews) and french canadians for cystic fibrosis
what is secondary prevention and what are some examples
procedures that detect and treat pre-clinical pathological changes
screening for down syndrome and other aneuploidies
screening for open neural tube defects
screening for structural fetal abnormalities
when is a routine ultrasound offered to all pregnant women
18-20 weeks
what are some soft markers on ultrasound associated with increased risk of fetal aneuploidy
thickened nuchal fold echogenic intracardiacs focus echogenic bowel choroid plexus cyst cerebral ventricles >10mm
what is a hypoplastic/absent nasal bone on prenatal ultrasound suggest
risk factor for Down syndrome
what are some examples of prenatal diagnostic tests
amniocentesis (>15 weeks)
chorionic villus sampling (10-14 weeks)
what causes short palpebral fissures
fetal alcohol syndrome
triangular face is associated with what syndrome
Russel silver syndrome
bifid uvula
submucous cleft palate
pierrre robin sequence features
glossoptosis
microretrognathia
airway obstruction
Nonsense
Missense
Silent
frameshift
Nonsense- stop codon therefore no protein or truncated protein produced
Missense- protein has new amino acid at site of mutation
silent- neutral, same amino acid
frameshift- deletion or insertion, usually introduces a premature termination
what is the testing for DMD
CK
MLPA of DMD gene or deletion/duplication analysis of DMD gene or targeted genetic testing of DMD gene
what is the test for detecting methylation syndrome
MS-MLPA
Prader-willi, angelmans, BWS
what is the best genetic test for down syndrome
karyotype
what are features of fetal alcohol syndrome
short palpebral fissures smooth/flattened philtrum thin upper lip micrognathia railroad track ears lower IQ, poor communication, memory, executive function
what is the teratogenic effect of valproic acid
NTD
what is fetal hydantoin syndrome
Caused by phenytoin and carbamazepine
IUGR DD microcephaly depressed nasal bridge ridged frontal suture hypoplastic nails/distal phalanges *
Lithium is associated with what in a newborn?
ebstein anomaly
What are the fetal effects of coumadin
stippled epiphyses
what are the fetal affects of ACE’s and ARBs
problems with renal development- renal tubular dysgenesis
what are 2 folic acid antagonists
MTX
aminopterin
fetal affects of thalidomide
bilateral limb deficiency- phocomelia
What is the genetic inheritance of VACTERL?
multifactorial
What gene is associated with CHARGE syndrome
CHD7
spinal muscular atrophy, how do they present?
results from progressive degeneration and loss of anterior horn cells in the spinal cord and the brain stem nuclei
Children present with symmetric muscle weakness beginning proximally then moving distally, hypotonia, areflexia/hyporeflexia, and tongue fasciculations.
The facial muscles are relatively spared; however, suck and swallow capabilities are typically affected. Fasciculations of the tongue are seen in most children, which is a defining physical examination finding not commonly seen in pediatric neuromuscular disorders.
How does NF type 2 present
Neurofibromatosis type 2, an autosomal dominant disorder, typically presents in the adolescent or early adult years with bilateral vestibular schwannomas that result in balance dysfunction, tinnitus, and hearing loss.
A unique ocular finding that can develop in childhood is posterior subcapsular lens opacity; this may be the first sign of NF2
What is anticipation?
With anticipation, a condition tends to become more severe and manifests at an earlier age as it is passed down from 1 generation to the next.
Seen with trinucleotide repeat disorders
what is variable expression
Variable expression occurs when the severity and presentation of disease manifestations differs among individuals with the same genotype.
what is penetrance
proportion of individuals with the mutation who exhibit clinical symptoms.
Penetrance is the probability that a gene will manifest clinically in an individual with a particular genotype. Incomplete or reduced penetrance is an all-or-none phenomenon. Incomplete penetrance occurs when an individual with a specific genotype does not express any signs or symptoms of the disorder.
what 2 tests are recommended for a child with intellectual disability
microarray
fragile x testing
what gene is associated with fragile x
FMR1 gene
what are key findings on physical exam for smith-lemli-opitz syndrome
cleft palate and syndactyly of the 2nd-3rd toes
severe cognitive impairment
Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations in the sterol Δ7-reductase gene located on chromosome 11q12-q13.
PHACES syndrome
p osterior fossa malformations h emangiomas a rterial anomalies c oarctation of the aorta and other cardiac defects, e ye abnormalities.
The Dandy-Walker malformation is the most common developmental abnormality of the brain.
5 years old kid w abdo pain, on u/s see intussusception; has hyperpigmented macules on lips
Peutz Jeghers syndrome
Ehlers-Danlos syndrome (3)
inherited connective tissue disorders caused by abnormalities in the structure, production, and/or processing of collagen.
rectal prolapse
mitral valve prolapse
joints hyper-extensibility
Which cardiac defect is most likely in a child with 22q11?
TOF
List 3 features of Pierre-Robin sequence
Cleft Palate
Micrognathia
Glossoptosis
list 5 common health problems for someone with turner’s syndrome
cardiac- bicuspid aortic valve
growth- short stature requiring growth hormone
hearing deficits
renal- horseshoe kidney
autoimmune- thyroid disease, celiac disease
WAGR
WAGR = Wilms tumor, aniridia, genitourinary anomalies, mental retardation
what hair loss thing is associated with down syndrome
Alopecia areata affects 6–10% of those with Down syndrome compared to the >2% prevalence in the general population
Waardenburg syndrome
dystopia canthorum, congenital hearing loss, heterochromic irises, white forelock`
3 syndromes associated with choanal atresia
CHARGE
crouzon syndrome
treacher-collins syndrome
Criteria for Rett syndrome
Criteria for Classic RTT – need all 5
- Period of developmental regression followed by stabilization/recovery
- Loss (partial/complete) of acquired purposeful hand skills
- Loss (partial/complete) of acquired spoken language
- Stereotypic hand movements – wringing (at midline), squeezing, clapping, mouthing, rubbing
- Gait abnormalities – dyspraxia or absence of ability
what are 3 syndromes associated with Pierre Robin sequence
22q11* think this first
Stickler syndrome * second
Treacher Collins
Stickler syndrome
Stickler syndrome, a connective tissue disorder, is associated with midfacial hypoplasia, cleft palate, Pierre Robin sequence, hearing loss, and eye abnormalities including high-grade myopia, cataracts, and increased risk for retinal detachment.
Treacher collins
Treacher Collins syndrome is an autosomal dominant disorder; the classic facial dysmorphology is characterized by underdevelopment of the zygomatic bones and mandible, downslanting palpebral fissures, prominent nose, micrognathia and retrognathia, external ear abnormalities, coloboma of the lower eyelid, absence of the lower eyelashes, and anterior hair displacement onto the lateral cheekbones.
Klinefelter syndrome
Klinefelter syndrome, or 47,XXY syndrome, is the most frequent chromosomal disorder in males with gynecomastia and small testes; the diagnosis is often missed until adulthood.
The classic presentation is of an older male adolescent or young adult with small testes, gynecomastia (38%), tall stature, long arms and legs, and possibly learning or behavioral difficulties.
The maternal quadruple screen is a serum screening test
performed between 15 and 22 weeks of pregnancy that measures 4 substances in the blood (α-fetoprotein, human chorionic gonadotropin, estriol, and inhibin-A) to ascertain risk for certain trisomies or open neural tube defects based on result patterns.
what are the two first line tests for children with global developmental delay and intellectual disability of unknown etiology?
Chromosomal microarray
fragile X testing
what does a sequence mean?
sequence is used to describe the consequence of a series or cascade of events, usually initiated by a single factor
The most common chromosome abnormality in first trimester spontaneous miscarriages is:
trisomy
In a Robertsonian translocation fusion occurs at the:
a) telomeres.
b) centromeres.
c) histones.
d) ends of the long arms.
centromeres
The presence of two or more cell lines from different zygotes in a single individual is known as:
a) mosaicism.
b) diploidy.
c) aneuploidy.
d) chimaerism.
chimaerism (two different zygotes)
Which of the following trisomy karyotypes has the mildest effect on human development?
a) 47,XXX
b) 47,XXY
c) 47,XX,+13
d) 47,XY,+21
47 XXX
You are asked to evaluate a well infant girl with
apparently isolated Pierre Robin sequence. Which of the following diagnostic tests is most likely to yield a useful clinical finding?
A. Chromosome analysis
B. Electrocardiogram (ECG)
C. Eye exam
D. FISH for del22q11.2
E. Skeletal survey
eye exam (Stickler)
Which of the following is not a chromosome instability syndrome? a) Klinefelter syndrome b) Ataxia telangiectasia c) Fanconi anaemia d) Bloom syndrome
klinefelter syndrome
Exon skipping is associated with:
a) nonsense mutations.
b) regulatory mutations.
c) RNA processing mutations.
d) silent mutations.
RNA processing mutations
Male to male transmission is a key feature of which pattern of inheritance?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked dominant
d) X-linked recessive
Autosomal dominant
Consanguinity shows a strong association with which pattern of inheritance?
a) Autosomal dominant
b) Autosomal recessive
c) X-linked dominant
d) X-linked recessive
autosomal recessive
Which of the following would be most useful in differentiating non-accidental injury (NAI) from osteogenesis imperfecta in a 5- month-old girl with unexplained fractures?
A. Blue sclerae
B. Healing fractures of different ages
C. Low socioeconomic status of the parents
D. Retinal hemorrhages
E. Type I collagen analysis
retinal hemorrhages
- do not occur with osteogenesis imperfects
The most common cystic fibrosis mutation consists of:
a) a deletion.
b) a duplication.
c) a substitution.
d) an insertion
deletion
delta 508 deletion
If both parents are affected with the same autosomal recessive disorder then the probability that each of their children will be affected equals ___.
a) 1 in 4
b) 1 in 2
c) 2 in 3
d) 1
1
Enzyme assay can be used to identify carriers of:
a) Cystic fibrosis.
b) Fragile X syndrome.
c) Oculocutaneous albinism.
d) Tay-Sachs disease.
Tay-Sachs disease
Which of the following is a feature of X-linked dominant inheritance?
a) Parental consanguinity
b) Transmitted by males only to females
c) Transmission only by females
d) Male to male transmission
Transmitted by males only to females
A 3-year-old girl has hypodontia, alopecia, and mild
developmental delay. Examination reveals hyperpigmented hyperkeratotic streaks. Her sister has severe developmental delay with seizures. Her mother has partial adontia and atrophic scalp hair. Which of the following clinical findings is most commonly
associated with this disorder?
A. Affected females can only have unaffected males or affected females.
B. Chromosome analysis of fibroblasts reveal an abnormality in 90% of cases.
C. Germline mosaicism is a common etiology.
D. One sees fewer than expected males in affected families.
E. 67% of cases represent new mutations
One sees fewer than expected males in affected families. incontinentia pigmenti (lethal in males)
A concerned mother brings her 18-month-old daughter to the pediatrician’s office because she has been intermittently constipated. Her mother became alarmed while changing her diaper straining to have a stool, she found some red, tissue bulging from the rectum. Which of the following procedures or laboratory studies is most like to identify the appropriate diagnosis?
A. Colonoscopy for Crohn disease.
B. Molecular analysis for Duchenne muscular dystrophy
C. Rectal biopsy Hirschsprung disease
D. Renal ultrasound for Beckwith-Wiedemann syndrome
E. Molecular analysis for cystic fibrosis
molecular analysis for cystic fibrosis
- rectal prolapse can be a sign of cystic fibrosis
High blood ammonia level occurs in:
a) galactosaemia.
b) Hurler’s syndrome.
c) ornithine transcarbamylase (OTC) deficiency.
d) phenylketonuria.
OTC deficiency
Which of the following conditions is a peroxisomal disorder?
a) Acute intermittent porphyria
b) Maple syrup urine disease
c) Medium chain acyl-CoA dehydrogenase deficiency
d) Zellweger syndrome
Zellweger syndrome
A newborn infant has the Robin sequence. The mother was diagnosed with arthritis in childhood and has had a retinal detachment. Which of the following is the most likely syndromic diagnosis? A. Acromesomelic dysplasia B. Rieger syndrome C. Stickler syndrome D. Treacher Collins syndrome E. Warburg syndrome
stickler syndrome
- Radial ray anomalies distinguished by the presence or absence of thumbs can provide a clue toward an appropriate diagnosis. In which of the following syndromes are thumbs consistently present?
A. Thrombocytopenia and absent radius syndrome
B. Fanconi anemia
C. Holt-Oram syndrome
D. VATER association
E. de Lange syndrome
Thrombocytopenia and absent radius syndrome
A 3 year old girl has severe developmental delay, microcephaly, no speech, grand mal seizures, and ataxic limb movements. Chromosome analysis and FISH testing for a 15q11 deletion are normal. Which of the following genetic tests would be most appropriate to order in trying to determine the underlying etiology?
A. Cholesterol/7-delhydrocholesterol ratio
B. FMR1 analysis
C. MECP2 sequence analysis
D. Methylation studies of chromosome 11p15
E. Uniparental disomy for chromosome 7
MECP2 sequence analysis
Incontinentia pigmenti
dominant X-linked disease.
characterised by skin, eye, teeth and central nervous system (CNS) abnormalities.
lethal in males
rash: blister like lesions often grouped in lines along the arms and legs (following lines of Blaschko)
what are the two GI obstructions with trisomy 21
hirschprung’s disease
duodenal atresia
what medical conditions are children with trisomy 21 at risk for in the future
- hearing loss
- otitis media
- refractive error
- cataract
- OSA
- leukemia
- hypothyroidism
- hirschprung’s disease
- seizures- particularly infantile spasms
- celiac disease
what investigations for T21 1 month- 1 year: age 1-5: 5-13: 13-21:
1month-1 year: repeat TSH at 6 months then annually repeat hearing at 6 months CBC at 1 year then annually screen for infantile spasms
age 1-5:
annual TSH
annual CBC
annual ophthalmology
5-13: annual TSH annual CBC annual hearing ophthalmology q 2 years screen for celiac, OSA screen for seizures, atlantoaxial instability
13-21: annual TSH annual CBC annual hearing ophthalmology q 3 years
