Genetics Flashcards
What is Wolf-Hirschhorn Syndrome
4p- deletion syndrome Greek helmet facies (ocular hypertelorism, prominent glabella and frontal bossing) growth deficiency microcephaly beaked nose hypertension short philtrum hypotonia congenital cardiac anomalies seizures developmental delay
What is Cri-Du-Chat Syndrome?
5p- deletion syndrome moon face with telecanthus (wide spaced eyes) down slanting palpebral fissures hypotonia short stature microcephaly high arched palate wide and flat nasal bridge intellectual disability cardiac manifestations in 33%
What is de Grouchy syndrome?
18q - microcephaly and developmental delay atretic or narrowed ear canals depressed midface protruding mandible deep-set eyes everted lower lip intellectual disability
What is 9p- or trigonocephaly
discrete exophthalmos, arched eyebrows, short neck with pterygium colli (bilateral web or tigh bank of skin of the neck extending from the acromion to the mastoid) long fingers, toes and cardiac abnormalites
What is see in Angelman syndrome
maternally derived 15 q11-13 jerky ataxic movements microcephaly characteristic gait hypotonia fair hair midface hypoplasia prognathism (large chin, mandible) seizures inappropriate bouts of laughter severe intellectual disability absent or very delayed speech
what is seen in Prader-Willi syndrome?
Paternally derived 15 q11-13 severe hypotonia at birth failure to thrive at birth followed by obesity later short stature small hands and feet hypogonadism mild intellectual disability
What is seen in Williams Syndrome?
7 q11.23 - deletion periorbital fullness with prominent down turned lower lip friendly cocktail party personality stellate pattern of the iris strabismus supravalvular aortic stenosis intellectual disability hypercalcemia
What is WAGR syndrome?
11p13- Wilms tumor Aniridia Genitourinary malformations Retardation (intellectual disability) wilms tumor in up to 50% by age 3 male genital hypoplasia (hypospadias, cryptorchidism) intellectual disability from IQ <35 to normal gonadoblastoma - esp girls, who have streak ovaries long face upward slanting palpebral fissures ptosis beaked nose poorly formed ears
What is seen in Alagille syndrome?
20 p12- AD mutation in the jagged-1 gene Triangular facies with pointed chin long nose with broad mid-nose bile duct paucity with cholestasis pulmonary valve stenosis and peripheral artery stenoses, tetralogy of fallot embryotoxon ocular defects prominent white ring of Schwalbe and iris strands that partially obscure the chamber angle butterfly vertebrae
What is DiGeorge or velocardiofacial syndrome
22q11.2 deletion
Catch 22
cleft palate
absent thymus
hypocalcemia (parathyroid hypoplasia / agenesis)
cardiac abnormalities (tetralogy of fallot > interrupted aortic arch > VSD > truncus arteriosus
short stature
behavior problems
hypoplasia of the auricle and external auditory canal
What is seen in Klinefelter syndrome?
47 XXY males who are tall with gynecomastia secondary sex development is delayed azoospermia small testes infertile
What is seen in Turner Syndrome?
45 X short stature ovarian failure / gonadal dysgenesis with lack of secondary sexual development webbed neck broad shield like chest posteriorly rotated ears lymphedema of the hands and feet 50% have cardiac defects of bicuspid aortic valve, coarctation of the aorta
What disorders are associated with Turner Syndrome
hashimoto thyroiditis alopecia carbohydrate intolerance vitiligo GI disorders ***Gonadoblastoma if they are a mosaic with a Y chromosome***, streak gonads must be removed
What is pierre robin sequence
mandibular hypoplasia
this displaces the tongue leading to cleft palate, glossoptosis
feeding and respiratory problems
What is hemifacial microsomia?
external ear anomalies (microtia, anotia, canal atresia and or preauricular tags
maxillary and/or mandibular hypoplasia
What is associated with hemifacial microsomia?
cervical vertebral anomalies in 33%
cardiac anomalies
renal anomalies (why a renal US is obtained in those with ear anomalies)
What is Goldenhar Syndrome
hemifacial microsomsia and epiblulbar lipodermoids (fatty-fibrous masses on globe) conductive hearing loss vertebral defects cardiac anomalies renal anomalies
What is seen with Brachio-Oto-Renal syndrome
brachial cleft fistulas or cyts
preauricular pits
cochlear and stapes malformation with mixed sensory and conductive hearing loss
renal dysplasia /aplasia
What is seen in Treacher-Collins Syndrome
AD mandibular and maxillary hypoplasia zygomatic arch clefts ear malformations down sloping palpebral fissures colobomata of the lower eyelids
What is seen in Achondroplasia
disproportionately short stature with rhizomelic shortening (short lengths of the most proximal segment compared to distal segments)
trident hands (3-4 digits more lateral, short hands, broad fingers)
macrocephaly
flat nasal bridge, prominent forehead, midface hypoplasia
What are children with achondroplasia at risk for?
serous otitis media motor milestone delay bowing of the legs orthodontic problems foramen magnum stenosis and/ craniocervical junction abnormalities causing cord compression -> apnea, quadriparesis, growth delay and hydrocephalus
What is seen in Osteogenesis imperfecta Type 1?
AD mildest and most common form blue sclera delayed fontanelle closure hyperextensible joints hearting loss stature is near normal multiple fracture before puberty
What do individuals with Osteogenesis imperfecta Type 1 have later in life?
hearing loss
scoliosis in their 20-30s
What happens with Osteogenesis imperfecta Type 2?
most severe form
usually results in death in infancy from respiratory insufficiency
numerous fractures and severe bone deformity
XR shows crumpled appearance
What happens with osteogenesis imperfecta type 3?
presents as a newborn with numerous fractures
severe short stature and many can not ambulate as bones can not support their own weight
neurologic complications such as hydrocephalus and basilar skull invagination
What occurs in osteogenesis type 4?
milder forms sclera are usually white or near-white delayed fontanelle closure fractures are present at birth shorter than average stature ***tibial bowing***
What is seen in Marfan Syndrome?
ectopic lentis aortic root dilatation or dissection family history systemic features (need 7 points plus one of the above) wrist and thumb sign (long fingers) pectus myopia mitral valve prolapse pneumothorax skin striae scoliosis or kyphosis high arched palate
What is the usual cause of death in someone with marfan syndrome?
aortic root dilation and rupture
What should be ruled out in someone who is suspected to have marfan syndrome?
homocystinuria
What are some of the findings in classic Ehleros Danlos syndrome
doughy skin
extra skin over the hands, feet and stomach
stretchy skin
skin is fragile and opens with slight trauma
easily bruising due to capillary fragility
abnormal scaring, with pseudotumors on heels, elbows and knees from abnormal scarring
hypermobile joints
What does someone with Ehleros Danlos need to be screened for?
mitral valve prolapse
proximal aortic dilatation
What is seen in neurofibromatosis type 1
AD
Need any 2 of the below:
café au lait spots, >6, > 0.5 cm in children > 1.5 cm in adolescents/adults
2 benign cutaneous neurofibromas or 1 plexiform neurofibroma
axillary or inguinal freckling
> 2 Lisch nodules (benign iris hamartomas)
optic glioma
sphenoid dysplasia or thinning of the long bone cortex with or without pseduarthrosis
1st degree relative with neurofibromatosis
What else needs to be observed in patients with neurofibromatosis type 1?
plexiform neurofibromas have a 10% risk of malignant transformation to peripheral sheath tumors
50% have ADHD, learning disorders or speech disorders
short stature, macrocephaly, hypertension, constipation and headaches
What is seen in Neurofibromatosis Type 2
AD
bilateral vestibular schwannomas (acoustic neuromas)- hearing loss, tinnitus, imbalance, and facial weakness
other CNS tumors:
intracranial meningiomas, spinal schwannomas, cranial nerve schwannomas ependymomas
lens opacities or cataracts
What is seen in tuberous sclerosis
AD ash leaf spots or hypo-pigmented macules shagreen patches facial angiofibromas forehead plaques ungula and gingival fibromas cortical tubers and subependymal nodules renal angiomyolipomas polycystic kidney disease
rhabdomyomas in infancy infantile spasms (treat with vigabatrin)
What cancers are seen in von Hippel-Lindau Syndrome
AD
for diagnosis:
2 or more hemangioblastomas in the CNS (esp cerebellum) or retina
or 1 hemangioblastomas and 1 of:
pheochromocytoma
endolymphatic sac tumors
cysts in the kidney / pancreas
renal cell carcinoma
pancreas involvement, neuroendocrine tumors
or 1 first degree relative with the disease and 1 of the above manifestations
what two syndromes are seen with PTEN hamartoma tumor syndrome
Cowden syndrome
Bannayan-Riley-Ruvalcaba syndrome
What is cowden syndrome?
high risk of benign and malignant tumors of thyroid, breast and endometrium
usually have macrocephaly, trichilemmomas (benign outer root of the hair sheath) papillomatous papules
What is bannayna-Riley-Ruvalcaba syndrome
macrocephaly, intestinal hamartomatous polyposis (not malignant but can grow to cause obstruction)
What defects are seen with Thalidomide
limb defects including missing limbs
ear malformations with deafness
What defects can occur if baby is exposed to carbamazepine in utero
< 1% risk of spina bifida with exposure during days 15-29
What defects can occur if baby is exposed to methotrexate in utero
increased risk of craniosynostosis, cranial facial abnormalities and limb defects
during weeks 6-9
What defects can occur if baby is exposed to ace inhibitors in utero
if exposed during 2nd and 3rd trimesters
increases the risk of renal dysgenesis, oligohydramnios, skull ossification defects
What defects can occur if baby is exposed to diethylstilbesterol in utero
use before 12 weeks gestation increases risk of vaginal adenocarcinoma at a later age
uterine anomalies, vaginal adenosis and male infertility
What defects can occur if baby is exposed to lithium in utero
use before 8 weeks
< 1% chance ebstein anomaly
What defects can occur if baby is exposed to phenytoin in utero
use in first trimester, 10% risk of
growth deficiency, developmental delays, craniofacial anomalies, hypoplastic phalanges / nails
What defects can occur if baby is exposed to retinoic acid in utero
serious malformations: similar to DiGeorge syndrome, microcephaly, facial nerve palsies, microtia, cardiovascular defects, thymic hypoplasia and genitourinary anomalies
What defects can occur if baby is exposed to streptomycin in utero
Use during the third trimester results in hearing loss
What defects can occur if baby is exposed to tetracycline in utero
use after 20 weeks is associated with bone and tooth staining
What defects can occur if baby is exposed to valproic acid in utero
Use in the first 30 days, 2% risk of spina bifida
1st trimmest : craniofacial abnormalities, preaxial defects
What defects can occur if baby is exposed to warfarin in utero
nasal hypoplasia stippled epiphyses
if used later than 6-9 weeks CNS effects
How is fetal alcohol syndrome diagnosed
substantiated maternal alcohol use and 2 of the following shortened palpebral fissures epicanthal folds hypoplastic nasal root short upturned nose hypoplastic or absent philthrum thin upper lip midface hypoplasia and 1 of the following: weight < 10th microcephaly length/height ratio < 10 and at least 1 developmental or learning problem
