Genetics & Metabolics Flashcards
(177 cards)
1
Q
Trisomy 13 genetics
A
- patau syndrome
- trisomy caused by maternal neurotic nondisjunction
- risk increases with maternal age
- can be suspected on prenatal screening
- confirmatory diagnosis with karyotype
2
Q
Trisomy 13 features
A
- facial: sloping forehead, eye abnormalities (small eyes, close together eyes, iris colobomas), low set abnormal ears, small jaw
- cleft lip and palate
- cutis aplasia congenita (helps distinguish from T18)
- midline defects
- central apnea high risk
- heart: VSD, ASD, ToF
- renal problems - multi cystic, horshshoe
- often die within 2 weeks of birth (cardio respiratory) (10% survive beyond 1yr)
3
Q
Trisomy 13 health surveillance
A
If they survive beyond neonatal period
- echo
- kidney ultrasound
- brain MR
- sleep study for central apnea
- monitor growth on T13 curve
- feeding assessments
- regular eye checks by optho
- development and intellectual delays common (most remain non verbal)
4
Q
Rett Syndrome
A
X linked
Hand wringing
Autistic behaviour
Female
Should be investigated for differential genetic cause of ASD or severe ID in female
MECP2 molecular testing for dx
5
Q
Sturge Weber
A
Mosaic somatic mutations
Port wine birthmark +/- brain involvement +/- glaucoma
Brain MR to diagnose
Optho consult for glaucoma
Overlap with Klippel-Trenaunay syndrome (mixed capillary/venous/lymphatic malformations involving bone and muscle in one limb)
Can have seizures, development problems, stroke-like episodes, headaches
6
Q
Lesch Nyhan Syndrome
A
Classic: kidney stones, gout, self-injurious behaviour, GDD, dystonia
X-linked recessive (boys)
If gout, think purine metabolism disorder (decreased enzyme or overproduction)
Allopurinol for gout treatment
Diagnose with HPRT enzyme analysis, high serum uric acid, high urine uric:Cr
7
Q
Cervical spine xrays in Down syndrome
A
onlyif symptoms:
Any child with neck pain, radicular pain, weakness, spasticity, changes in gait, hyper-reflexia, change in bowel/bladder or signs of myelopathy warrant plain cervical spine xrays in neutral position.
8
Q
clinical manifestations of A1AT
A
Lung disease (ex bronchiectasis, emphysema) :(occurs with severe genotype)
PFT: reduced expiratory air flow, hyperinflation, low diffusion capacity
Liver disease (hepatoma, cirrhosis):
Prolonged neonatal jaundice
Cholestasis symptoms
Mildly elevated liver enzymes
Can develop portal hypertension
Skin & soft tissue:
Panniculitis (rare but classic, can occur with all genotypes)
Cellulitis like areas or tender red nodules on trunk or proximal extremities
Nodules tend to ulcerate spontaneously and discharge oily yellow fluid
Persistent cutaneous vasculitis
Cold urticaria
Acquired angioedema
9
Q
PFT finding to suggest A1AT
A
Anyone with fixed airflow obstruction on spirometry should be screened for A1AT
10
Q
Male with ambiguous genitalia, edema and proteinuria
A
Denys Drash syndrome
11
Q
Cafe au lait macules and axillary freckling
A
Neurofibromatosis
12
Q
Neurofibromatosis type 1
A
-Cafe au lait macules 6+ (most on trunk and extremities)
-Axillary or inguinal freckling
-Iris lisch nodules 2+ (identified on slit lamp - need optho assessment)
-Neurofibromas 2+
-Bone abnormalities (Osteopenia, Scoliosis, Long bone dysplasia)
-Optic gliomas (optho!!) - can extend to hypothalamus and cause precocious puberty
autosomal dominant
13
Q
Wilm’s tumor + ambiguous genitalia
A
denys drash
14
Q
abdo distension, hematuria, fevers, anorexia, pallor, weight loss
A
wilms tumor
15
Q
Wilm’s, absent iris, undescended testes, GDD
A
WAGR syndrome
Wilms
Aniridia: absent colored region of eye
GU abnormalities: undescended testes, hypospadias, internal genital/urinary anomalies
Retardation
16
Q
Frasier syndrome
A
congenital nephropathy, ambiguous genitalia in males, underdeveloped gonads that may lead to cancer. Early ESRD in childhood
17
Q
ADHD, ataxia, intellectual dissability and adrenal insufficiency
A
x linked adrenoleukodystrophy
18
Q
progressive weakness, intellectual impairment, hypertrophy of calves
A
ducehenne muscular dystrophy
x linked recessive
19
Q
cerebellar ataxia, oculomotor apraxia, choreoathetosis, telangiectasia, immunodeficiency
A
ataxia telangectasia
autosomal recessive
symptom onset before age 5
20
Q
E.coli sepsis related to metabolic condition
A
galactossemia
21
Q
Wilms Tumor Genetic Syndromes
A
WT1 mutation
- denys drash
- fraser syndrome
- WAGR
Bottom line: WT1 mutation = Wilms Tumor, Kidney disease, abnormal genitals
Beckwith Wiedemann also has wilms tumor association
22
Q
Dent disease
A
proteinuria & nephrolithiasis
X-linked
nephrolithiasis
low molecular weight proteinuria,
hypercalciuria
Fanconi Syndrome (proximal tubule defect- glycosuria, amino aciduria, phosphaturia)
23
Q
Consanguinity common gene inheritance
A
think autosommal recessive
24
Q
Smith Lemli Opitz Syndrome
A
Autosomal recessive (think consanguinity)
Mutation in 7-dehydroxycholesterol-delta7 reductase- the final step in cholesterol synthesis.
Have low cholesterol and buildup of cholesterol precursors and many congenital anomalies
Type 1 (classic): Prenatal and postnatal growth retardation, microcephaly, ptosis, anteverted nares, syndactyly of 2nd and 3rd toes, and severe cognitive impairment. 70% are males- genotypic makes have ambiguous genitalia or complete sex reversal with female genitalia. Associated with pyloric stenosis
Type 2: acrodysgenital syndrome- lethal within 1 yr, severe malformations, postaxial polydactyly, extremely abnormal external genitalia. Cleft Palate have been seen in Type II
Rx= dietary cholesterol (egg yolks lol) and HMGCoA reductase inhibitors to prevent precursor buildup
25
Turner syndrome heart
left sided heart problems
- bicuspid AV
- aorta things
26
Achondroplasia
Autosomal Dominant- FGFR3 mutation
The most common short-stature skeletal dysplasia marked by rhizomelia (disproportionate length of proximal limb), macrocephaly, midface hypoplasia, and normal cognition
Can get spinal stenosis and small foramen magnum
Growth hormone NOT effective
27
VACTERL investigations
CXR (butterfly vertebrae)
abdo US (kidney problems
no genetic testing
VACTERL Association
V- Vertebral anomalies- CXR (spine xray)- butterfly vertebrae
A- anal atresia/anorectal anomalies- examine
C- Cardiac
TE- TEF
R- enal- ultrasound
L- limb
28
Gilbert syndrome
A familial, nonhemolytic, unconjugated hyperbilirubinemia
Most common hereditary hyperbilirubinemia syndrome (5-10% white ppl)
Autosomal recessive
Defect in promoter region for UDPGT-1 (enzyme that makes bilirubin water soluble)- making it only partially effective
Unlike Crigler Nijjar (also defect in UDPGT)- it often presents after puberty and not associated with chronic liver disease.
Mild, fluctuating levels of bili. No treatment. Only really important in some chemotherapies because this enzyme breaks it down
29
What test for Beckwith Wiedemann
DNA Methylation test
30
Tests requiring DNA methylation test
Uniparental disomy syndromes
Beckwith Wiedemann
Prader Willi
Angelman
Loss of methylation on mom
31
Beckwith Wiedemann
big tongue
keep eating
organomeagly
32
Neonate with persistent hypoglycemia, seizure and absent septum pellucidum
Septo optic dysplasia
- midline brain defects (think absent corpus callosum or septum pellucidum)
- can get panhypopit (and pituitary hormone issues)
33
Septo-optic dysplasia
Also called “optic nerve dysplasia syndrome”
Classic “triad” or any combo of:
**Optic nerve hypoplasia (nystagmus, visual impairment)
Pituitary gland hypoplasia (75%, most common is GH deficiency)
Midline brain defects (absent corpus collosum, corpus collosum dysgenesis)**
can have seizures
Causes: genetic (unknown), cocaine in pregnancy, other environmental
34
Isolated polydactyly
pretty normal. can remove the digit
Typically autosomal dominant in inheritance
If isolated, especially with family history, no other workup
Treatment is ablation of digit (Suture ligation or surgical depending on how formed)
35
Ash leaf spots
hypopigmented lesions
can be seen with Wood's lamp (blue light)
tuberous sclerosis
- tubors in brain
autosomal dominant with variable expressivity
36
McCune Albright
Triad of- **precocious puberty (peripheral), polyostotic disease (fibrous dysplasia), abnormal pigmentation with irregular borders**
Autonomous hyperfunctioning of 1 or more gland (pituitary, thyroid, and adrenal glands). GNAS mutation which stimulates cAMP and activates receptors including those for ACTH, TSH, FSH, LH). In short, get lots of endocrinopathies (hyperthyroid, cushings, etc)
37
neurocutaneous disorders
Neurofibromatosis 1/ 2
Fanconi Anemia
Russell Silver Syndrome (Cutis aplasia, cardiac stuff)
Noonan Syndrome
Bloom Syndrome
Tuberous Sclerosis (usually hyPOpigmented)
McCune Albright
Sturge Webber
38
Males only transmission
x linked recessive
39
Mccune Albright
bone problems (Polyostotic Fibrous Dysplasia)
large cafe au lait macules
endocrine problems - precocious puberty
40
hypoketotic hypoglycemia
fatty acid oxidation disorder (acidosis)
hyperinsulinism (no acidosis; insulin inhibits ketosis)
41
Anions minus cations
Na - (HCO3 + Cl) = AG
**Sometimes sources say (Na+K)- (HCO3+Cl)
Wide Anion Gap >12 (+/-2) = Acid Gain
Causes of wide anion gap metabolic acidosis = MUDPILES
42
A newborn baby is found to have choanal atresia.
CHARGE syndrome
(coloboma, heart defects, atresia choanae (also known as choanal atresia), growth retardation, genital abnormalities, and ear abnormalities)
43
CHARGE syndrome
- Coloboma
- Heart defects (commonly TOF)
- Atresia of the choanae
- Retardation of growth & development
- GU anomalies
- Ear anomalies (ear abnormalities, SNHL)
Other:
asymmetric facial nerve palsy, cleft lip/palate, EA/TEF
usually sporadic mutation
single gene testing - SHD 7
44
Trisomy 21 surveillance
Birth
- echo before 1 mo age
- TSH as newborn
- cbc within 1 week
Annual
Hearing screen
CBC
TSH
Optho q 2 years
Celiac only if symptomatic
cervical spine screen if symptomatic
sleep study by age 4
45
Carnitine-acylcarnitine translocase deficiency
Fatty acid oxidation disorder
- avoid prolonged fasting
46
Beckwith Wiedemann associated cancers
Associated health conditions:
Embryonal cancer (until at least age 8):
- Wilm’s tumour
- Hepatoblastoma
- Neuroblastoma
- Rhabdomyosarcoma
Screening:
AFP (for hepatoblastoma) & abdo US q3mo until 4yo
Then renal US including adrenal glands q3mo until 8yo (then less frequently)
Periodic CXR and urine HVA/VMA (for neuroblastoma) have been suggested but low yield so not in most screening protocols
DNA methylation testing (MS-MLPA)
47
Beckwith Wiedemann symptoms
Pits and creases (ears)
Macrosomia, macroglossia
Hypoglycemia (neonatal) - pancreatic beta cell hypertrophy
Facial nevus simplex and other vascular malformations
Asymmetric growth, hemihypertrophy
Characteristic facies: midface hypoplasia and infraorbital creases
Omphalocele, umbilical hernia
Premature and overgrown at birth
Organomegaly
Enlarged adrenal cortex
Cardiomegaly or structural cardiac anomalies
Renal abnormalities: nephromegaly, nephrocalcinosis, etc.
Advanced bone age
48
Prader Willi Symptoms
*In Infancy:*
Poor suck
Need tube feeding
Poor growth/FTT
Central hypotonia
*Childhood: 4Hs and an O*
Hypotonia
Hypogonadism
Hypomential/devel delay
Hyperphagia
Obesity (truncal)
Other physical features: almond shaped eyes, thin upper lip, small hands/feet
*DNA methylation studies*
growth hormone helps in Prader Willi
49
Digeorge syndrome testing
FISH for 22q11
or microarray
test PTH and calcium
immune workup (T and B cells, immunoglobulins, vaccine titers)
renal US for anomalies
50
Williams syndrome testing
FISH for 7q
think if HYPERcalcemia
51
CATCH 22
Digeorge:
CHD: VSD, TOF, interrupted aortic arch
Abdomal facies
thymic hypoplasia
cleft palate
hypocalcemia
22q11 deletion syndrome
52
Baby has tetrology of fallot - what genetic disorder do you test for
DiGeorge (22q11 deletion)
53
congenital central hypoventilation syndrome
primary central apnea, hypercarbia, and hypoxemia.
presents within first several weeks of life
associated with risk of Hirschsprung and neuroblastoma
they should have holter every 12 mo - risk of sinus pauses (may need pacemaker)
PHOX2B
54
Noonan Syndrome symptoms
hypertelorism, big forehead, webbed neck
MSK: pectus, wide nipples
CHD: right sided lesions (PS), cardiomyopathy
Cryptorchidism
Hypotonia
Failure to thrive
Abnormal bleeding and bruising
multi gene testing panel
*similar to Turner's but hypertrophic cardiomyopathy for heart lesion and has cryptorchidism*
55
Smith Lemli Opitz
microcephalic
cleft palate
syndactylyl 2nd and 3rd toes
low cholesterol problem (think opposite of familial hypercholesterol)
56
Myotonic muscular dystrophy
Affects all muscles
- hypotonia at birth
- inverted v of upper lip
- shitty muscles everywhere - look thin, muscle wasted
- reflexes preserved (different from Duchenne late illness)
- CK not as high as other muscular dystrophies
Autosomal dominant
PCR testing
57
2year-old boy with hypoglycemia, triangular faces with 4 café au lait macules. Ht 3rd, wt 3rd, HC 50th.
Russel Silver
58
Russel Silver syndrome
Small for gestational age (asymmetric SGA)
FTT
Relative macrocephaly, *triangular face*, fifth finger clinodactyly
Feeding difficulties
Micrognathia with narrow chin
Hypoglycemia
Cafe au lait macules
Testing: DNA methylation studies
59
Russell Silver acute illness
measure ketones and blood sugar - risk of ketotic hypoglycemia when ill
60
Cafe au lait ddx
NF1
Legius syndrome (SPRED1): no neurofibromas or lisch nodules
NF2: vestibular schwannoma
Noonan: congenital cardiac defects, dysmorphisms
Constitutional mismatch repair genes mutations: GI cancers
Russell-Silver syndrome: Small for gestational age
McCune-Albright syndrome: endocrinopathies, fibrous dysplasias
Fanconi anemia: hematologic abnormalities, multiple congenital abn
61
2 year old boy 3 days of vomiting and diarrhea. Lethargic. Glucose low (2.4?). Ketones 2+. Most likely diagnosis?
hyperketotic hypoglycemia
62
Adrenocorticoleukodystrophy
think if:
- tanned (signs of addison disease)
- ADHD symptoms
- ataxic
LCFAD
x linked
affects the brain and adrenals (Addison like picture)
Dx:
- check long chain FA to confirm diagnosis
- brain MR after diagnosis
- cortisol w/u after diagnosis
63
ELFIN FACIES
Williams syndrome
*supravalvular AS and coarctation*
*hypercalcemia*
*stelatte iris*
64
Beckwith Wiedemann tumor association
Hepatoblastoma highest risk - check AFP every few months
65
Neonate with severe hypotonia and requiring gavage feeding. often puffy feet and hands
Prader Willi
66
Timing for achondroplasia neuroimaging sreening
by 1 month of age, MR brain
67
What test is warranted for kids with new developmental delay?
chromosomal microarray
68
3 week old . PH 7.1. High ammonia, high lactate. Etiology?
organic acidemia
(ex. methylmalonic acidemia)
69
If cafe au lait spots, refer to?
optho for optic glioma and Lisch nodules (need slit lamp to help with diagnosis
70
Turner syndrome features
XO
sporadic inheritance (can have mosaicism)
Classic things:
- webbed neck
- broad chest, wide spaced nipples
- low birth weight
- short stature
- wide carrying angle
- low hairline
71
Turner syndrome systemic conditions
- screen for celiac disease
- hypothyroid
- CHD: coarc and bicuspid AV valve
- renal malformations
- hearing loss from AOM
- ovarian failure - delayed puberty
- short stature (can improve with GH)
72
Diagnostic testing for galactossemia
elevated GALT level urine
73
Galactossemia inheritance
autossomal recessive
74
Galactossemia features
Jaundice, hepatomegaly, hepatic failure, ascites, splenomegaly
Feeding difficulties, vomiting, poor weight gain
Hypoglycemia
Seizures, lethargy, irritability
Aminoaciduria
Cataracts, vitreous hemorrhage
Increased risk for E coli sepsis
Pseudotumor cerebri can occur and cause a bulging fontanelle
75
Organic acidemia
- accumulation of toxic acid metabolites
- excrete the organic acids in urine (test the urine)
- appear in newborn period or infancy typically
- life threatening episode of AG Metabolic acidosis first presentation
- AG from ketosis
- frequently neutropenic or pancytopenic d/t bone marrow suppression
dx: urine organic acids
Highest risk during periods of catabolism (fasting)
76
Urea cycle defect
normally urea cycle helps convert nitrogen into urea to be excreted
- often presents similar to sepsis with lethargy --> coma
- hyperammonemia
- *central hypoventilation leading to respiratory alkalosis* due to the toxic metabolites
- high ammonia
- hormal glucose
- anion gap
- respiratory alkalosis
77
Klinefelters
XXY
can cause primary hypogonadism
ambiguous genitalia (varying degrees)
infertility later in life
often developmental delay
*delayed puberty*
tall stature
high FSH and LH
low testosterone
Karyotype dx
78
Marfan
connective tissue disorder
aortic anneurysm, disection, rupture is risk
AV valve prolapse
rhythm problems
eye problems - refer to optho
can get dislocation of the lens (ectopia lentis)
refer to optho and cardio if questioning
79
High ammonia with respiratory alkalosis
urea cycle defect
80
High ammonia with acidosis AG
aminoacidopathy or organic acidemia
81
Hypoketotic hypoglycemia
fatty acid oxidation disorder or hyperinsulinism
82
Hypoglycemia with high lactate
glycogen storage disorder
83
High lactate constantly
mitochondrial disorder
84
liver failure in newborn
galactossemia
85
gram negative sepsis in newborn (ex. ecoli)
galactossemia
86
Smith Lemli Opitz
slOw, dont grOw, weird tOes,
87
Central congenital hypoventilation syndrome
PHOX2B mutation
can't sense hypercarbia
need PSG in first yr life
arrhythmia so need holter
urine screen and US for neuroblastoma
Hirschsprung
88
genetic conditions with cafe au lait macules
Neurofibromatosis 1
Neurofibromatosis 2
Fanconi Anemia
Russell Silver Syndrome
Noonan Syndrome
Bloom Syndrome
Tuberous Sclerosis
McCune Albright
89
syndromes with craniosynostosis
Crouzon Syndrome
Apert Syndrome
Pfeiffer Syndrome
Saethre Chotzen
Muenke Syndrome
90
3 syndromes requiring PSG before age 1
achondroplasia
congenital central hypoventilation syndrome
prader willi *not necessairly before 1
91
cocaine teratogen association
placental abruption
92
most common cardiac defect from perinatal alcohol use
septal defects - ASD/VSD
93
fetal hydantoin syndrome
microcephaly
cleft lip
hypoplastic nails
hypoplastic distal phalanges (short stubby tips of fingers)
94
maternal diabetes teratogen features
- sacral agenesis (caudal regression syndrome)
- small left colon syndrome
- hypertrophic cardiomyopthy
95
maternal PKU during pregnancy
if mom's disease is well controlled, limited effects on baby
if maternal phenylalanine is high and uncontrolled, risk of:
- IUGR
- microcehaly
- heart defects
- ADHD
96
syndrome strongly associated with cutis aplasia
patau (Tri 13)
97
baby with IUGR, prominent occiput, overlapping fingers and rockerbottom feet
trisomy 18
Edwards
98
down syndrome heart disease
AVSD > VSD > ASD > ToF > PDA
99
girl with delayed puberty, short stature and followed by cardiology
Turner syndrome
100
Turner syndrome heart defects
left side - turn left!
bicuspid aortic valve
coarctation
long QTc
101
baby with hypocalcemia and recurrent infections and cleft palate
DiGeorge 22q11.2
C-cardiac (conotruncal)
A-abnormal facies
T-thymus hypoplasia
C-cleft lip
H-hypocalcemia
102
diGeorge heart disease
conotruncal
- ToF
- interrupted aortic arch
- truncus arteriosus
103
autosomal dominant diseases examples
Achondroplasia
Crouzon syndrome
CHARGE
Ehlers-Danlos
Familial adenomatosis Polyposis
Hereditary breast/ovarian cancer
Li-Fraumeni syndrome
Marfan syndrome
Neurofibromatosis 1
Neurofibromatosis 2
Noonan syndrome
Osteogenesis imperfecta
Treacher Collins syndrome
Tuberous sclerosis complex
Huntington disease
Denys-Drash syndrome
104
autosomal recessive diseases examples
Congenital adrenal hyperplasia
Cystic fibrosis
Phenylketonuria
Sickle cell disease
Tay-Sachs disease
Congenital myasthenia syndrome
Jeune asphyxiating thoracic dystrophy
Alpers-Huttenlocher syndrome
Leigh syndrome *can be mitochondrial*
105
x linked recessive examples
Duchenne muscular Dystrophy
Hemophilia A/B
Lesch-Nyhan syndrome
106
x linked dominant examples
Incontinentia pigmenti
Rett syndrome
Fragile X syndrome
107
mitochondrial inheritance examples
*moms will pass mtDNA to all children; dad's don't pass on*
*hetoplasmy occurs when there is more than one population of mitochondria in the oocyte*
- MELAS
- Leigh syndrome (also AR)
108
uniparental disomy examples
patient inherits two copies from one paren't chromosome (instead of one) leading to identical chromosomal markers on both
- prader willi (maternal - inherit 2 from mom; where is papa?!)
- angelman (paternal - inherit 2 from dad; missing mom )
- beckwith wiedemann
- Russel silver (maternal - inherit from mom)
109
trinucleotide repeat exansion examples
DNA appears as repeat sequences of three bases. disease occurs when number of rpts exceeds a threshold
- fragile X
- Friedreich ataxia
- huntington
110
methotrexate teratogen exposure
craniosynostosis
craniofacial anomalies
underossified skull
limb defects
MTX FUX UP DA BONES IN DA BABY ESP DA SKULL
111
Angiotensin receptor blockers in late pregnancy teratogen effects
rena dysgenesis
skull ossification defects
oligohydramnios
112
tobacco teratogen effects
premature delivery
miscarriage
stillbirth
113
warfarin teratogen effects
nasal hypoplasia
stippled epiphysis
developmental delay
114
valproic acid teratogen effects
spina bifida / neural tube defects
craniofacial
hypospadias
115
isotretinoin (Accutane/vit A) teratogen effects
CNS defects
absent thymus
conotruncal defects
intellectual disability
miscarriage
116
baby with large occiput, rockerbottom feet and overlapping fingrs
trisomy 18
117
crouzon syndrome
craniosynostosis
big forehead
hypertelorism, proptosis
cleft lip/palate
NORMAL intelligence, normal extremities
*CROUZON CRANIOSYNOSTOSIS FCKED UP CRANIUM* but smart
AD inheritance
most common craniosynostosis syndrome (but occurs in 1/16 million)
118
Pfeiffer syndrome and Apert syndrome
Pfeiffer
- craniosynostosis
- hearing loss
- THUMB/BIG TOE problems (curved out) +/- syndactylyl
Apert
- craniosynostosis
- hearing loss
- PROMINENT SYNDACTYLY
119
is turner syndrome associated with advanced maternal age?
no
120
puberty in turner syndrome
delayed puberty
amenorrhea
breast development limited to breast buds, minimal pubic hair
infertile d/t streak ovaries with premature ovarian failure
significant growth retardation d/t estrogen insufficiency
121
list 3 genetic syndromes with short stature
Turner syndrome
Noonan syndrome
prader willi
122
Turner syndrome unique features
XO
shield chest, wide spaced nipples, webbed neck
heart: left sided lesions
short stature
delayed puberty/amenorrhea
increased with autoimmune disorders
normal intelligence
123
Noonan syndrome unique features
webbed neck, low set ears, down slanting palpebral features
heart: right sided lesions (pulm stenosos, hypertrophic CM)
cryptorchidism
coagulopathy
short stature
*Facial features: droopy noonan - droopy eyes (down slanting palpebral), droopy ears (low set and posterior rotation), droopy neck (webbed)
**NOT DROOPY TESTICLES**
AKA Doppy from Snow White
124
which of the following syndromes appear normal at birth?
Turner
Klinefelter
Noonan
DiGeorge
Klinefelter
often confused with Marfan d/t tall stature later in life
delayed puberty and infertility
125
Klinefelter features
XXY
normal appearing at birth
Tall stature
GU: tiny testes and penis, hypospadias
Delayed puberty and infertility (testosterone
replacement in adolescence if no puberty)
+/- development/learning disabilities
126
boy with big ears, big testicles and intellectual disability
fragile X
127
fragile X genetics
x linked dominant
FMR1 gene
PCR diagnosis
CGG repeats
- premutation 55-200 rpts
- full mutation 200+ rpts
128
fragile x features
mild to mod intellecutual disability (apparent by age 2)
face: long, narrow, big ears, big forehead
big testicles
fam hx of miscarriages in mom (female carriers can be symptomatic and often have premature ovarian failure)
129
NF 2 pearls
AD
Think
- schwanomas
- gliomas
- meningiomas
- neurofibromas
other: cataracts, hearing loss, tinnitus, cafe au lait
130
workup and investigations for NF1
NF1 molecular genetic testing
MRI brain (*only if symptomatic*)
annual optho
annual BP monitoring
monitor for scoliosis
routine tumor surveillance (incr risk of pheo, gliomas, juvenile myelomonocytic leukemia, breast ca)
131
investigations and wokrup for tuberous sclerosis
genetic testing TSC1 and TSC2
brain MR (rpt q3 yr)
EEG
Echo
optho
renal US
*if sz, use vigabatrin*
132
incontentia pigmenti
x linked dominant
weird rashes present at birth
classically blistering rash at infancy (mistaken for HSV) but follows lines of Blashko
rash changes over time --> hyperpigmented --> hypopigmented
at risk for seizures and retinal detachment
133
angelman syndrome
UPD (paternal inheritance; missing mom)
features
- microcephaly
- seizures
- sleep problems
- ataxia
- happy demeanor, innappropriate laughter, anger outbursts
- developmental delays, non verbal
do an EEG d/t increased risk seizures
134
lesch nyhan inheritance and prominent features
x linked recessive
hyperuricemia d/t abnormal purine metabolism
self injurious behaviour, gout, developmental delays
tx: allopurinol
135
Rett syndrome inheritance
MECP2
x linked dominant (the boys die)
136
Rett syndrome investigations
mollecular genetics for MECP2 to confirm
ECG for prolonged QTc
EEG for risk seizures
137
suprastar memory aid for which syndrome
Williams syndrome
stellate iris
Super personality "cocktail party"
supravalvular aortic stenosis
138
williams syndrome features
suprastar
- supravalvular AS
- super personality
- stellate iris
elfin facies
intellectual disability
hernias, rectal prolapse
endo: hypothyroid, hypercalcemia
139
williams syndrome investigations
chromosomal microarry for dx
serum/urine calcium (hypercalcemia)
thyroid function (hypothyroid)
echo (supravalvular AS)
renal bladder US
hearing screen
optho
140
timing of PSG for baby with achondroplasia
often before leaving hospital d/t risk of central apneas due to foramen magnum stenosis
may need head imaging as well to assess for degree of stenosis
141
growth hormone for achondroplasia
no role - ineffective
142
precautions for patients with achondroplasia
avoid contact sports, diving, gymnastics d/t risk of atlantoaxial instability
respiratory insufficiency d/t central apneas - routine management of sleep apnea
143
activity avoidance for marfan vs. ehlers danlos
Marfan
- weight lifting and contact sports
- wind instruments/scuba diving (ptx)
- pregnancy is high risk
Ehlers danlos
- activities with high strain on joints
- weight lifting IF aortic dilation
144
marfan syndrome eye finding
ectopia lentis
145
ectopia lentis ddx
Marfan (most common cause)
- usually bilateral and occurs most often in the superotemporal direction
Homocystinuria (second most common)
- usually bilateral and in 60% of cases occurs in the inferior or nasal direction
146
medications used in osteogenesis imperfecta
bisphosphonates
growth hormone
147
pierre robin features plus myopia and skeletal abnormalities
Stickler syndrome
148
who hates genetics the most?
Michelle (WRONG!)
John
149
syndromes associated with omphalocele
T21
beckwith Wiedemann
150
wilms tumor associated conditions
- Beckwith Wiedemann
- denys drash
- WAGR
- Frasier
151
beckwith wiedemann increased tumor risk
embryonal tumors
- Wilms (nephroblastoma)
- Neuroblastoma
- hepatoblastoma
*embryonal tumors think blastomas
152
alpers huttenlocher syndrome
triad: intractable epilepsy, psychomotor regression, liver disease
autosomal recessive, mitrochondrial
153
leigh syndrome
mitochondrial, autosomal recessive
classic findings
- lactic acidosis
- FTT
- hypotonia
- peripheral neuropathy
- hypertrophic cardiomyopathy
154
MELAS
mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes
development is normal. symptoms begin in childhood with stroke like episodes
Arginine used for acute treatment of stroke like episodes
mitochondrial inheritance
155
CHARGE Syndrome
AD inheritence
C- coloboma
H- heart (conotruncal, arch)
A - atresia choanal
R- retardation of GROWTH
G- GI/GU (microphallus)
E- ear (helix malformation, deafness)
E - extremities (clubfoot, absent tibia, hand anomalies - finger like thumb, hockey stick palmar crease, square palm)
OTHER features
- TEF or esophageal atresia
- dysphagia
- facial palsys
- orofacial clefts
156
investigations for CHARGE syndrome
C - ophtho
H - echo
A - temporal bone CT
r
G - renal bladder US
E - audiology
157
how many features do you need for vacterl
at least 3 of the following
Vertebral
Anal atresia
Cardiac
TE fistula
Renal anomalies
Limb anomalies
158
rhizomelic long bone shortening
proportionally shorter proximal limb bones compared to distal long bones
seen in achondroplasia
159
eye problems in Marfans
ectopia lentis (up and out)
glaucoma
cataracts
160
homocystinuria
*similar to marfans*
marfanoid body habitus
ectopia lentis (down)
intellectual disability!!
thrombotic events!!
dx: measure serum homocysteine levels
161
hypertension in NF1
screen for renal artery stenosis and pheo
162
ectodermal dysplasia
can't sweat -- at risk of hyperthermia
conical teeth
163
hypotonia, gavage feeding and puffy hands and feet with cryptorchidism newborn
prader willi
164
165
key pearl for urea cycle defect
High ammonia
may be alkalotic or mildly acidotic
low urea!
166
key pearl for organic acidemia
profound metabolic acidosis (much more than urea cycle defect)
also have high ammonia
normal urea
167
Phenylketonuria
aminoacidopathy
autosommal recessive
incidious onset! no crisis
features: microcephaly, GDD, rash, mood
NMS is usual diagnosis
tx: breast milk or phenylalanine free formula
168
homocystinuria
looks like marfan's but will have intellectual disability and can have recurrent thrombosis
ectopia lectis (down)
no metabolic crisis
life long methianine avoidance
169
maple syrup urine disease
autosomal recessive
presents with **acute crisis**
--> headache, lethargy, vomiting
neonate: hypertonic, coma
high ketones!
170
methylmalonic acidemia
organic acidemia
presents with metabolic acidosis and high ammonia and high urea
elevated urine organic acids
171
OTC deficiency
urea cycle defect
high ammonia!!! low/normal urea!!
x linked (but females can be affected)
liver transplant is curative
172
glycogen storage disease
metabolic acidosis but NO ammonia elevation
presents after a few months when infant starts stretching feeds
unable to store/use glycogen so goes hypoglycemic with fasting BUT able to make ketones (unlike FAOD) so therefore ketotic hypoglycemia
173
pompe disease
glycogen storage disorder type 2 (doesn't really present like glycogen storage disease type 1 - no hypoglycemia, rarely any lab findings, mainly problems with glycogen storage deposition)
- cardiomegaly
hypotonia
hepatosplenomegaly
174
baby with hypotonia, respiratory insufficiency, cardiomegaly and ECG with short PR interval - what condition?
Prader Willi
Noonans
neonatal lupus
Pompe disease
pompe disease (Glycogen storage type 2)
175
condition that causes a false positive newborn screen for galactossemia
G6PD
176
fatty acid oxidation disorder presentation
crisis during times of fasting or poor intake
hypoketotic hypoglycemia --> lethargy, sz, coma
may have hepatitis
dx with acylcarnitine profile (increased) and carnitine profile (decreased)
acute tx: high dextrose infusion. No lipids!
avoid prolonged fasting
177
bone finding in congenital hypothyroidism
distal femoral epiphysis is often absent on xray
