Genetics/Derm Flashcards
Beckwith Wiedemann syndrome mode of inheritance(s)
50%: loss of methylation on maternal chromosome 11
20%: paternal uniparental disomy
5%: gain of methylation on maternal chromosome 11
Klippel-Trenaunay-Weber
port-wine stains with superficial vascular abnormalities; present at birth with underlying hypertrophy of bones or soft tissues
Sturge-Weber
unilateral port wine stain on head and neck; unilateral face in 1stor 2nddivision of trigeminal nerve distribution
Also have mental deficiency, seizures, hemiparesis contralateral to facial lesion, ipsilateral tramline intracortical calcifications, glaucoma, optic atrophy, buphthalmos
cutis aplasia
congenital absence of skin involving epidermis and dermis; can occur ANYWHERE, most common on scalp or trunk. Benign form is AD. Re-epithelizlize over several months. Associated with limb defects
Maternal MMI use
Staph scalded skin syndrome
fever, irritability, conjunctivitis, crusting around eyes/mouth; rapidly recovers without scarring
Infantile hemangiomas ________ until 6-8 months, then ______. Which require intervention?
grow for 6-8 months, then involute. 75% involute by age 7 without scarring or recurrence
Require intervention if large, ulcerate, become secondarily infected, or compromise airway or vision b/c location
CHARGE syndrome
autosomal dominant; mutation in gene chromodomain helicase DNA-binding protein 7 (CHD7), mutation detected in only about 67% of patients
MAJOR criteria = coloboma, choanal atersia/stenosis, CN dysfunction, ear anomalies
Down’s syndrome causes
95% of cases result from nondisjunction, 47 chromosome karyotype
3-4% unbalanced translocation
1-2% mosiac
nevus sebaceous of Jadossohn
hamartoma composed of abnormal amount of sebaceous glands and other adnexal structures. Solitary well-defined oval or linear yellow-to-orange waxy plaque with super imposed hair loss
Becker’s nevus
initially flat, hyperpigmented patch at birth
Cobb syndrome
cutaneomeningospinal angiomatosis, cutaneous angiomas and vascular abnormalities of spinal cord
Cutis marmorata
occurs in neonates less than 1 mo of age, T18, T21, Cornelia de Lange syndrome, or hypothyroidism. Presents with diffuse symmetric reticulated erythematous patten involving extremities and trunk
Incontinentia pigmenti
X-linked dominant. Linear inflammatory, pigmented warts, macular hyperpigmented streaks and whorls on trunk and extremities, hypopigented streaks that atrophy in childhood
Apert syndrome
(acrocephalosyndactyly) - AD, mutation in fibroblast growth factor receptor 2 gene. Fusion of the hands, skull, feet bones
Phenytoin maternal use increases risk of what condition
PHEN
cleft lip/palate
Hypoplastic face, small head, heart defects
Embryopathy
Hypoplastic nails / digits, Neuro defects
Bohn nodules
Ebstein pearls
Epulis
Ranula
Bohn nodules - 1-2 mm gray-white or yellow, on maxillary alveolar ridge
Ebstein pearls are on hard palate
Epulis - single, soft pedunculated nodule over gingiva of anterior maxillary ridge, multiple nodules
Ranula - translucent lesion that arises from floor of mouth and may appear blue
The different blots
Southern blot: DNA is digested and exposed to DNA probe
Northern: hybridization of labeled DNA probe to digested RNA fragment
Western: proteins are separated based upon size and charge and specific antibody is used as probe to identify protein
Dot blot: patient’s DNA is amplified in region of known mutation and applied to membrane
FISH vs microarray
FISH: synthesis of single-stranded DNA probe that is complementary to sequence of interest, tagged with fluorescent marker (Trisomies, prader-Willi, Angelman, cri du chat, Digeorge, other genetic dz)
Microarray: analysis of molecular fragments of DNA to determine of genomic gain or loss has occured
Name genetic abnormalities for OI, achondroplasia, Stickler syndrome, Ellis-van Creveld syndrome, Jeune syndrome
OI: COL1A
Thanatophoric dysplasia / achondroplasia: FGFR3
STickler syndrome: COL2A
Ellis-van Creveld syndrome: EVC1, 2
Jeune syndrome: IFT80
Trisomy 13
VSD, cleft lip/palate, narrow hyperconvex fingernails, cutis aplasia
Majority of T 13, 18, and 21 is extra chromosome of _______ origin
maternal
Fragile X syndrome
MACROcephaly (large ears, large head, large testes)
X-linked dominant
dermis of premature infants have _____ collagen fibers compared to term infants
fewer
Eccrine or sweat glands of infants < 30 weeks are ________
NONfunctional (anhidrosis)
Eccrine glands of term infants have ______ activity for first week of life, ______ neurologic control for up to 3 years
decreased x2
Preterm infants have significantly ______ SA - V ratio compared to term infants and adults
increased
Preterm infants have ______ number of melanosomes compared to term infants
1/3
Linkage Studies
indirect method to diagnose genetic diseases, uses loci that are near each other on same chromosome or “linked” to determine of an individual has inherited chromosome containing a disease gene
Williams syndrome
7q11.23 deletion of elastin gene
50-70% have supravalvular subaortic stenosis, hypoplastic nails, prominent lips, hoarse voice, stellate iris pattern, renal anomalies
WAGR Syndrome
11p13 = WAGR sndrome
Wilm’s tumor
aniridia
GU
MR
Rubenstein-Taybi
16p13.3 deletion - cardiac (PDA, VSD), broad thumbs and toes, downward slanting palpebral fissures, hypoplastic maxilla, hirsutism, hypotonia, DD
How does a PCR work
amplifies specific DNA sequence from genomic DNA by using two primers on either side of sequence of interest; DNA is denatured, hybridized with specific primers flanking area of interest, and then extended
Holt-Oram syndrome
cardiac (ASD), upper limb defects, absent/hypoplastic thumbs, narrow shoulders, hypertelorism
Thanatophoric dysplasia
AD - FGFR3 (same as achondroplasia)- telephone receiver curved long bones, flat vertebral bodies
recurrence risk is same as baseline population risk bc new mutation leads to skeletal dysplasia
Trisomy 18
cardiac, clenched hands with overlapping digits, rocker bottom feet, single UA, short sternum
Trisomy 13
midline abnormalties (cardiac), cutis aplasia, polydactyl, narrow hyperconvex fingernails, cleft lip/palate, holoprosencephaly
Rapid degradation of misfolded protein = ________
Mislocalization of misfolded protein, accumulation and toxicity = _______
Rapid degradation of misfolded protein = CF, PKU
Mislocalization of misfolded protein, accumulation and toxicity - A1At, SCD, Gaucher dz
What is 2nd most common cause of mental deficiency after T21
Fragile X (X-linked dominant)
Cell-free DNA originates from _____
Placenta
Continuous turnover of vilous trophoblast results in shedding of apoptoci material containing cell-free DNA in maternal circulation
Likelihood of second anomaly in infant with prenatal dx of clubfoot
60%
Mosaic Turner’s syndrome puts you at increased risk of
gonadoblastoma
Enhancer
sequences that bind transcription factors that affect recruitment of RNA polymerase. Cis-acting, on same strand of DNA but can often be located at significant distance from coding region of gene
Leigh syndrome
mitochondrial d/o with progressive neurodegenerative dz
Cystic fibrosis cause
caused by point mutation in CFTR gene, problem with DNA polymerase
Triploidy can signify _____
placentomegaly
amniotic band syndrome is a form of
direct disruption of developing tissue
Prevalence of minor congenital anomalies
20%
Legius syndrome
6 or more cafe au lait macules; axillary or inguinal freckling; macrocephaly, learning disability. overlapping with NF-1
McCune Albright - gene?
large cafe au lait macules, coast of maine, lines of blaschko. precocious puberty. GNAS1 gene
Steroids for infantile hemangiomas are useful during what stage
Proliferative
Listeria - cutaneous findings are common in early or late dz?
Early - present at birth. white plaques on umbilical cord
Bifid ribs
usually unilateral, asymptomatic
Enhancers and promotors
noncoding regulatory DNA sequences and can BOTH bind transcription factors. Enhancers can act from a distance (promoters are always located in close proximity)
Angelman syndrome is caused by a contiguous gene disorder. what does that mean
deletion of multiple genes that are adjacent to one another
Syndactyly
most common type of congeital abnormality of UE, failure of separation of two fingers 5-8 weeks GA; sporadic, usually no genetic transmission
Under histology - IP vs Varicella/herpes
eosinophils, giant cells respectively
High humidity isolates carry risk of colonization with
pathogenic bacteria
Epidermolysis bullosa
inherited mechanobollous disorder characterized by development of blisters after skin is exposed to mild friction or trauma. Can be simplex, junctional, or dystrophic
Tx: supportive care
Difference between EB simplex, junctional, and dystrophic
simplex = superficial above basal cell layer of epidermis (AD), no scarring
junctional - junction of epidermis an dermis (AR), yes scarring
Dystrophic - bullae are dep within upper portion of dermis, AD and AR; disfiguring scarring
Cutis aplasia syndromes, inheritance
autosomal dominant
T13 or 4p syndrome
How to culture SSSS
nasopharynx; fluid of lesions is sterile
Major criteria for CHARGE
Coloboma, Choanal Atresia, CN dysfunction, characteristic ear
What is collodion membrane
membrane is a thickened stratum corneum that swells from amniotic fluid exposure. The tightened membrane around the infant causes ectropion (eversion of the lower eyelids), eclabion (eversion of the lips), and may lead to sausage-like swelling of the digits
significant risk for hypothermia, hypernatremic dehydration, and infection
nonbullous congenital ichthyosiform erythroderma
Describe Becker’s Nevus vs Epidermal nevus
Becker’s nevus - flat, hyperpigmented patch at birth
Epidermal nevus - wart-like lesion, linear, on limbs / trunk / scalp. Associated with skeletal defects, ocular complications, CNS
Apert syndrome? What is similar to it?
Apert syndrome - FGFR2 gene, craniosynostosis, VSD, pulmonary stenosis, overriding aorta
Apert and Crouzon are similar
Genes for TS and NF
TS - chromsome 9/16
NF - Chromosome 17
Bohn nodules vs epulis vs radula
bohn nodules - kind of like Epstein pearls, but on maxillary alveolar ridge (Ebstein’s pearls on hard palate)
Epulis - single, soft pedunculate nodule her gingiva of anterior maxillary ridge
Ranula - translucent lesion from floor of mouth (blue)
What causes skeletal dysplasia vs dysostoses
Skeletal dysplasia - abnormal organization of cells during early patterning events of skeletal development
Dysostoses - malformations of bones as result of insult during organogenesis
Southern vs Northern blot
Southern blot: DNA probe to DNA fragment
Northern: DNA probe to RNA fragment
Genes for OI, achondroplasia, Stickler, Ellis-van Creveld, Jeune
OI - COL1A
Thanatophoric / achondroplasia - FGFR3
Stickler - COL2A
Ellis-van Creveld - EVC1, 2
Jeune - IFT80
Who do you get extra chromosome for trisomies from?
Mom!
Preterm vs term skin differences (melanosomes, sweat glands)
Preterm have 1/3 amount of melanosomes compared to term (photosensitivity)
Eccrine / sweat glands < 30 weeks are nonfunctional; term infants have decreased activity for first week
Preterm has fewer # collagen elastic fibers
What are linkage studies
Linkage studies provide an indirect method to diagnose genetic diseases.
This analysis uses loci that are located near each other on the same chromosome or “linked” to determine if an individual has inherited a chromosome containing a disease gene. DNA polymorphisms can be used as markers. These loci are physically linked, but may not be functionally related.
Genes for WAGR, BWS, Rubenstin-taybi, Williams syndrome
11p13 = WAGR syndrome
11p15 = BWS
16p13.3 = rubenstein-taybi anomalies - cardiac (patent ductus arteriosus, ventricular septal defect, atrial septal defect), broad thumbs and toes, downward slanting of palpebral fissures, hypoplastic maxilla, hirsutism, hypotonia, and developmental delay.
Williams syndrome (chromosome 7)- hypoplastic nails, prominent lips, hoarse voice, stellate iris pattern, entail deficiency, renal anomalies, transient hypercalcemia, supravalvular aortic stenosis
Smith Lemli Opitz Syndrome
autosomal recessive
elevated 7 deoxycholesterol
What cardiac anomalies in DiGeorge?
conotruncal = iAA, TA, TOF
Thymus and parathyroid glands are from 3rd-4th pharyngeal pouch
Advanced paternal age and genetic risks?
increased risk of NEW gene mutations (Achondroplasia, Apert, Crouton, NF I, OI, RB, Thanatophoric dysplasia, Pfeiffer syndrome)
PCR vs FISH
PCR - amplify specific DNA sequence from genomic DNA by using primers on either side of sequence of interest
FISH - expose cells to single-stranded DNA probe tagged with fluorescent marker and allowing for hybridization
Holt-Oram Syndrome?
AD, variable expression - Heart + hand (hypo plastic or abnormally shaped thumbs, narrow shoulders hypertelorism)
Genetic inheritance of achondroplasia / thanatophoric dysplasia
80% de novo mutation, rest are inherited AD. Both are FGFR3
Features of T13
midline defects, heart, cutis aplasia, holoprosencephaly, cleft lip/palate
Risk of clubfoot with other anomalies?
60%
What are you at risk of with mosaic turner?
Gonadoblastoma
What is the promoter region / poly-A tail / Enhancer
Promoter region - where RNA polymerase and TF bind to initiate transcription
poly-A tail - mRNA transport and stability
Enhancer - bind TF that affect recruitment of RNA polymerase
What is Leigh Syndrome
mitochondrial
progressive neurodegenerative disease
What is Legius syndrome (what is similar to?)
6 or more cafe au last, no other stigmata of NF-1; AD; SPRED1 gene; mild DD
NF-2 - acoustic neuromas
Derm findings of early-onset Listeria
skin lesions presents at birth, white plaques on umbilical cord
Skin findings don’t happen in late onset dz
Bullous pemphigoid vs pemphigus syphiliticum vs bulbous impetigo vs SSSS vs EB
Bullous pemphigoid - AI, ab against BP antigen. Tense blisters on hands and feet. IgG and C3 on basement membrane on immunofluorescent staining
Pemphigus syphilitcum - congenital syphilis, early onset dz
Bullous impetigo - gram stain / culture of fluid , first two weeks life
SSSS - sterile bullae
Epidermolysis bullosa - 4 types - simplex, junctional dystrophic, mixed
- Immunofluorescence and electron microscopy
5 + 2 = type 7 collagen
BP is characterized by autoantibodies directed against the NC16A domain of collagen XVII, whereas patients with epidermolysis bullosa acquisita have autoantibodies against the NC1 domain of type VII collagen.
What syndrome associated with bifid ribs?
Gorlin Goltz
What do you see on histology for incontinentia pigmenti?
eosinophils; same as E-Tox
Inheritance of EB simplex, junctional, dystrophic
AD, AR, AR+AD
