Genetics Flashcards
Pregnancy screening for Down syndrome?
low AFP, low estriol, high HCG, high inhibin
What is brachydactyly?
Short, broad fingers and toes
Anticipatory guidance for Down syndrome (6)?
1) Echo in newborn period
2) Ophthalmology before 6 months
3) Hearing eval before 6 months
4) TSH/FT4 at 3, 6, 12 months, then annually
5) Vision screening at 4 years
6) All immunizations
Future risk of Trisomy 21?
If Mom <35yo, risk is 1% (different if Downs is due to translocation or mosaicism)
Characteristic Edwards syndrome (Trisomy 18) (6)?
1) IUGR
2) MR
3) Rocker bottom feet
4) Clubfoot/clenched fist with overlapping fingers
5) CHD–most often VSD with dysplastic valves
6) Microcephaly
Mortality in Edwards?
50% by 1 week of age, 40% by 1 year of age (usually due to central apnea)
Characteristic findings in Patau syndrome (Trisomy 13) (8)? (Think midline!)
1) Cleft lip
2) Post-axial polydactyly
3) Holoprosencephaly
4) CHD
5) Hypoplastic or absent ribs
6) Genital abnormalities
7) Abdominal wall defects
8) Cutis aplasia
Mortality in Patau?
80% die within 1st month (median survivial is 2.5 days)
Characteristic findings in mosaic Trisomy 8?
Deep palmar and sole creases
Characteristic findings in Wolf-Hischhorn syndrome (4p-) (6)?
1) “Greek helmet” facies (ocular hypertelorism, prominent glabella, frontal bossing)
2) Growth deficiency
3) Beaked nose
4) Hypotonia
5) CHD (50%)
6) Seizures (90%)
Characteristic findings in Cri-du-chat (5p-) (6)?
1) “Cat’s cry” (due to anatomic change in larynx)
2) Telecanthus (decreased medial palpebrus distance)
3) Hypotonia
4) Short stature
5) MR
6) CHD (33%)
Characteristic findings in De Grouchy syndrome (18q-) (5)?
1) Atretic or narrowed ear canals (classic!)
2) Microcephaly
3) Developmental delay
4) “Frog-like” leg position
5) MR
Characteristic finds of Prader Willi syndrome (paternally derived 15q11-13) (6)?
1) Severe hypotonia
2) Obesity after newborn FTT
3) Short stature
4) Small hands and feet
5) Hypogonadism
6) Mild MR
Characteristic finds of Angelman syndrome (maternally derived 15q11-13) (6)?
1) Jerky ataxic movements (“happy puppet”)
2) Hypotonia
3) Seizures
4) Inappropriate bouts of laughter
5) Severe MR
6) Absent or severely delayed speech
Characteristic findings in Williams syndrome (7q11.23-) (6)?
1) Friendly “cocktail party” personality
2) Stellate pattern of iris
3) Strabismus
4) Supravalvular aortic stenosis
5) MR
6) Hypercalcemia
Characteristic findings in WAGR syndrome (11p13-) (5)?
1) Wilms tumor (up to 50%, usually by 3yo)
2) Aniridia
3) Male GU abnormalities (hypospadias, cryptorchidism, micropenis, hypoplastic scrotum)
4) MR
5) Also, possible gonadoblastoma
Characteristic findings in Alagille syndrome (20p12-) (6)?
1) AD inheritance
2) Bile duct paucity with cholestasis
3) PV stenosis and peripheral artery stenoses
4) Posterior embryotoxon
5) Skeletal defects (butterfly vertebrae)
6) Triangular facies
How soon does symptomatic cholestasis occur in Alagille syndrome?
In the first 3 months of life
Most common cardiac manifestations in Alagille syndrome?
Peripheral and branch PS (67%) and tetralogy (7-16%)
Characteristic findings in 22q11.2- syndrome (6)?
1) Cleft palate
2) Thymic aplasia/hypoplasia (immune deficiency)
3) Parathyroid gland aplasia/hypoplasia (hypocalcemia)
4) CHD (tet>interrupted arch>VSD>truncus)
5) Short stature
6) Behavioral problems
Heart defect in Turner syndrome?
Coarctation of the aorta; bicuspid aortic valve
Inheritance and gene involved in achondroplasia?
AD; FGFR3 on chromosome 4p16.3
Other keys with achondroplasia (2)?
1) Foramen magnum stenosis
2) Usually new mutation; rate increases with increasing paternal age
Mode of inheritance for all osteogenesis imperfecta?
AD (affecting collagen)
Characteristics of type I OI?
Mildest form–blue sclerae, delayed fontanelle closure, hyperextensibility, hearing loss, normal stature, multiple fractures (rare birth fractures)
Defect in type I OI?
Decreased Type 1 collagen
Characteristics of type II OI?
Most severe form–newborn death due to respiratory insufficiency
Defect in type II OI?
Disrupted collagen formation
Characteristics of type III OI?
Newborn fractures, short stature, difficulty ambulating, neuro complications (hydrocephalus, basilar skull invagination)
Characteristics of type IV OI?
Milder form, white sclerae, delayed fontanelle closure, birth fractures, short stature, tibial bowing
Mode of inheritance for Marfan syndrome?
AD
Most common cause of death in Marfan’s?
Cardiac–aortic root dilation and rupture
Direction of lens dislocation in Marfan’s?
Up and out
Direction of lens dislocation in homocystinuria?
Down and in
Defect in Marfan’s?
Fibrillin gene (FBN1)
Mode of inheritance for Ehlers-Danlos?
AD
Characteristic features of Ehlers-Danlos?
Hyperextensible skin, hypermobile joints, easy bruising/bleeding, dystrophic scarring
Cardiac problems with Ehlers-Danlos?
MVP and aortic root dilation (like Marfan’s)
Diagnostic criteria for NF-1 (need 2/7)?
1) >6 CAL spots >0.5cm before puberty or >1.5cm after puberty
2) >2 neurofibromas of any type or 1 plexiform neurofibroma
3) Axillary or inguinal freckling
4) Optic glioma
5) >2 Lisch nodules (iris hamartomas)
6) Sphenoid dysplasia or thinning of long bone cortex
7) 1st degree relative with NF-1
Mode of inheritance of NF-1?
AD (but 60% of cases are de novo; also with wide phenotypic expression, even in 1 family)
Mode of inheritance for NF-2?
AD
Diagnostic criteria for NF-2?
1) Bilateral acoustic neuromas, OR
2) 1st degree relative with NF-2 AND either unilateral acoustic neuroma, 2 of other CNS tumors, or lens opacity
What percent of plexiform neurofibromas (NF-1) can become malignant peripheral nerve sheath tumors?
10%
Other CNS tumors in NF-2?
Meningiomas, spinal schwannomas, cranial nerve schwannomas, ependymoma
Effects of acoustic neuromas?
Hearing loss, tinnitus, imbalance, facial weakness
Mode of inheritance of tuberous sclerosis?
AD (wide phenotypic variability even within 1 family)
Characteristics of TS?
1) “Ash leaf” hypopigmented macules (enhance with Wood’s lamp)
2) Shagreen patches (oval nevoid plaques)
3) Facial angiofibromas
4) Forehead plaques
5) Ungual and gingival fibromas
6) PCKD (with TSC2)
Other complications of TS?
1) Infantile spasms (50% of kids with IS will have TS)
2) Cardiac rhabdomyomas (multiple!)–may regress over time
Mode of inheritance for von Hippel-Lindau syndrome?
AD (VHL tumor suppressor gene; highly penetrant)
Diagnostic criteria for vHL?
1) 2 or more hemangioblastomas in CNS (usually cerebellum) or retina, OR
2) 1 hemagngioblastoma with either pheochromocytoma, endolymphatic sac tumors, kidney/pancreas cysts, RCC, neuroendocrine tumors of pancreas, OR
3) 1st degree relative and 1 of above
Teratogens–thalidomide?
Days 34-50–limb defects and ear malformations
Teratogens–carbamazepine?
Days 15-29–spina bifida
Teratogens–MTX?
Weeks 6-9 at >10mg/week–craniosynostosis, craniofacial abnormalities, and limb defects
Teratogens–ACE inhibitors?
2nd & 3rd trimesters–renal dysgenesis, oligo, skull ossification defects
Teratogens–diethylstilbestrol?
Before 12 weeks–vaginal adenocarcinoma in offspring of fetus
Teratogens–lithium?
Before 8 weeks–Ebstein anomaly
Teratogens–phenytoin?
During 1st trimester–fetal hydantoin syndrome (growth deficiencies, DD, craniofacial anomalies, hypoplastic phalanges/nails) or vitamin K deficiency
Teratogens–retinoic acid?
Weeks 2-5–DiGeorge-like features, microcephaly, facial nerve palsies, microtia/EAC anomalies, CV defects, thymic hypoplasia, GU anomalies
Teratogens–streptomycin?
3rd trimester–hearing loss
Teratogens–tetracycline?
After 20 weeks–bone and tooth staining
Teratogens–valproic acid?
1st 30 days–spina bifida; 1st trimester–craniofacial abnormalities, preaxial defects
Teratogens–warfarin?
Weeks 6-9–fetal warfarin syndrome (nasal hypoplasia and stippled epiphyses), CNS effects, or spontaneous abortion
Maternal exposure–alcohol?
Fetal alcohol syndrome–facial defects, growth deficiency, cognitive abnormalities (most frequently documented cause of MR)
Maternal exposure–cocaine?
Increased risk of miscarriage, stillbirth, premature delivery, fetal ICH
Maternal exposure–cigarettes?
Low birth weight; if heavy, miscarriage, prematurity, stillbirth
Maternal exposure–mercury (fish)?
Cerebral atrophy, seizures, DD
Maternal diseases–diabetes?
Sacral agenesis, holoprosencephaly, congenital heart defects (glucose control is vital!)
Maternal diseases–HTN?
Before 20 weeks–miscarrage; after 20 weeks–IUGR, placental insufficiency, placental abruption or previa
Maternal diseases–hyperthermia (hot tubs and fevers)?
Days 14-30–neural tube defects (if extensive and prolonged)
Maternal diseases–SLE?
Before 20 weeks–miscarriage; after 20 weeks–stillbirth, prematurity, congenital heart block
