PhysDi - Clinical Genetics (pics) Flashcards
When should a patient be referred for genetic evaulation?
- If they present with a group of specific
clinical features of a known condition - If they have clinical characteristics
suggesting dysmorphic features and/or
cognitive disabilities - If they have a family history of a specific
genetic condition
What is the most important component of a medical history in genetics?
family history - 3 generations
Genetics PMH
- childhood illnesses or disabilities (ex: deafness)
- preterm birth or postnatal complications
- growth delay/developmental issues
- hospitalizations
- surgical history (cleft palate, etc)
- major adult illnesses
- cancer history, any prescursor lesions
OB history in genetics
- intrauterine drug exposure
- prenatal complications
- prenatal testing
- spntaneous abortions, stillbirths
- T.P.A.L: term births, preterm briths, abortions, live briths
Why should ethnic and racial background be noted as part of the medical history?
certain geographic, ethnic, and racial groups are at relatively high risk for otherwise rare genetic disorders (Ex: Ashkenazi Jewish ancestry)
Recommended questions for family history to obtain informtion on key genetic issues
- heath problems that run in family
- cancer, heart disease, other adult onset medical conditions at an early age
- intellectual/learning disabilities
- early deaths (stillbirhts, infant deaths etc.)
- extreme/unexpected reactions to anesthesia
- problems w/ pregnancy, infertility, or brith defects
How do you record a family history for genetic purposes?
- as a pedigree
- include first and second degree relatives
- note unusual diseases (breast cancer in male)
- single relative w/ multiple cancers
- bilateral cancers in paired organs
- disease onset <40 yo
- family members w/ precursor lesions (colon polyps)
Benefits of pedigrees
- help visualize disease inheritance risk
- visually superior than list form
- obtain data from both sides of family
- uses 3 generations minimum
What to ask about when building a pedigree
- spontaneous abortions
- stillbirths
- infertillity
- children relinquished for adoption
- deceased individuals
- consanguintiy if indicated
What to take into account when interpretting a pedigree
- size of family
- number of unaffected relatives
- types of dx
- age at onset
- adoption
proband
family member who is first diagnosed for a specific genetic disorder
Pedigree Key
Inheritance of Red/Green color blindness (X-linked recessive) pedigree
What inheritance patter is this pedigree?
autosomal dominant
X-linked dominant pedigree example
Social history in genetics
- should include exposure to teratogens/chemicals:
- tobacco, ETOH, drug use
- occupational exposure risk
- asbestos
- chemical warfare in military
- radiation exposure
- behavioral and social issues
Preconceptual/prenatal medical history “red flags”
- genetic disorder/congenital abnormality in family
- 2 or more pregnancy losses
- unexplained infertility
- ethnic predisposition
- mother > 35 at time of delivery
- abnormal maternal serum screening
- abnormal fetal US
- teratogen exposure
- maternal condition affecting fetus
- parents w/ close biological relationship
Pediatric medical history red flags
- malformations/dysmorphic features
- abnormal newborn screening
- abnormal developent
- congenital hearing loss
- congenital blindness or cataracts
- fam history
- development of degenerative neuro disorders or unexplained seizures
Adults medical history red flags
- family history
- diagnosis of common disorder w/ earlier age onset than typical ( like cancer, heart disease, etc.)
- unusual manifestation of disease
- pediatric indications that have not yet been evaluated
Instruments for physical exam
- sliding digital calipers
- hand held ruler
- paper/flexible ruler
- camera
- FAS (facial photographic analysis software)
microcephaly
anencephaly
acrocephaly
craniofacial disorder refers to ?
an abnormality of the face and/or head:
- jaw size and position
- cleft palate
- missing bones
- premature closure of skull fibrous joint (sutures)
- hypoplasia
micrognathia
- reduced length and width of mandible
- noted from front
retrognathia
- posteriorly positioned lower jaw, set back from face
- noted from side
epicanthal fold def.
- skin fold of the upper eyelid covering the inner corder of the eye
- can be normal in very yound children
- more common in asians and native americans
- associated w/ Trisomy 21
epicanthal fold photo
How would you document this appearance?
pronounced or prominent medial epicanthal fold present b/l
hypertelorism definition
an increased interpupillary distance (>2 SD above mean or 97th percentile)
hypotelorism definition
a decreased interpupillary distance (> 2 SD below mean or <3rd percentile)
hypertelorism pic
hypotelorism pic
palpebral fissure
- space b/w the medial and lateral canthi of the open eyelids
- in adults, measures about 10mm vertically and 30 mm horizontally
Eye measurements; IPD, PFL, ICD
short palpebral fissure
long palpebral fissure
telecanthus
increased distance b/w the inner canthi
Coloboma
-keyhole deficiency of iris
Coloboma can be associated w/ what things?
- CHARGE syndrom
- Cat eye syndome
- Patau syndrome (Trisomy 13)
- Treacher Collins Syndrome
- can also be a normal varient
What to look at for dysmorphic features of the mouth
- look at philtrum length and smoothness
- upper lip thinness
- smooth patterns (can be normal) but often associated w/ genetic syndromes or FAS
FAS example
Dysmorphic feature of nose - low nasal bridge
Types of congenital ear deformities
- microtia: underdeveloped, very small outer ear
- anotia: missing 1 or both ears
- simple ear: lack of interior detail, flat pinna
- protruding ears: more than 2 cm from head
- cupped ears: flattened or rolled outer ears
- cryptotia: upper ear underneath the scalp skin
- Stahl ear: pointed outer ear
Dysmorphic features of the digits
- clinodactyly: inward curving of 5th finger
- brachydactyly: shortening of digits
- syndactyly: fusion of two digits
- polydactyly: extra digits
- unusual shape: tapered, clubbed, broad thumbs
tapered digits
What is this condition?
clinodactyly
finger clubbing
What condition is this?
Syndactyly
Musculoskeletal physical exam features
- limb length
- height
- arm span
- joint hypermobility
Dysmorphic features of the skin and hair
- pigmentation: hypopigmentation/hyperpigmentaiton
- hair quality, texture, pattern, distribution
- albinism: autosomal recessive inheritance caused by mutation
Cafe au lait macules are associated w/ what?
neurofibromatosis
How can genetic conditions produce neurocognitive impairments?
- structureal brain malformation
- aberrant signaling involving genes that play important neurological roles
- inborn errors of metabolism (not enough of needed substrate or accumulation of toxic metabolite)
- developmental delay
Clinical features at birth in Down Syndrome (Trisomy 21)
- low set ears
- hypotonia
- simian crease
- wide space b/w 1st and 2nd toe
- flat face
*Cause is chromosomal abnormality, not inherited mutation
Clinical features later on in down syndrome
- upslanting palpebral fissures, epicanthal folds, midface hypoplastia, and small dysplastic pinnae
- generalized hypotonia
- cognitive disabilities (mild to moderate)
- assocaited congenital heart disase and GI anomalies
Trisomy 18 (Edwards Syndrome) clinical findings
- small infants for gestational age
- dymorphic features:
- characteristic facies (micrognathia, cleft palate)
- prominent occiput
- malformed ears
- overlapping fingers
- rocker-bottom feet
- congenital heart disease (ventricular septal defect or PDA)
Trisomy 18 (Edwards) overview
Turner syndrome clinical features
- short stature
- broad chest, wideset nipples
- low hairline
- webbed neck
- cubitus valgus
- lymphedema of hands and feet
Turner Syndrome
Treacher Collins Syndrome clinical features
- underdeveloped zygomatic bone and maxilla
- sad looking face, eyes slant down
- celft palate
- ear deformities and hearing loss
- can have respiratory problems
- wide range of severity
- normal intellect
Treacher Collins pic
