Term
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Definition
-Human genome contains 3164.7 million chemical nucleotide bases
-Total number of genes is estimated at 30K
-Almsot all (99.9%) nucleotide bases are exactly the same in all people |
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Term
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Definition
-Meiosis: forms the gametes (sex cells) and this is where the variety in our genes comes from
-Genotype: Genetic make up of an individual
-Phenotype: physical expression in an individual
-Allele: specific form of a gene
-Heterozygote: two different alleles at a gene location
-Homozygote: same two copies of an allele at a gene location
-Loci (Locus): gene location
-Pedigree: shaded in means the person is affected by Dz; circles are girls and boys are squares; women on the right; triangle is a pregnancy loss |
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Term
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Definition
-Family Hx: include 3 generations; include ethnic background; age of Dx; age of death
-Medical Hx
-Developmental Hx
-Physical and dysmorphology exam
-Genetic testing |
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Term
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Definition
-EX: Neurofibromatosis, Marfan, 22q1 I deletion (DiGeorge)
-Nonpenetrance, variable expression, late onset, new mutation
-Males and females can both be affects; 50% chance offspring will be affects (on parent affect and one not); each pregnancy carries a 50% risk
-Both parents have disorder: 25% chance offspring unaffected |
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Term
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Definition
-EX: CF, PKU, Sick Cell
-Both parents are carriers: 25% chance the offspring will be affected
-Males and females affected; carriers unaffected
-Only on parent is a carrier: no affected children; 50% carriers
-One parent is affect and the other NOT carrier: ALL children unaffected carriers
-One parent carrier and other affected: 50% affects and 50% carriers
-Sibling of affected child has 2/3 chance of being a carrier |
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Term
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Definition
-EX: X-linked rickets
-NO M-M transmission
-Affected males have NO affected sons but ALL affected daughters
-Both male and female offspring of female carriers have 50% risk of inheriting phenotype
-Usually lethal in utero for males |
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Term
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Definition
-EX: Hemophilia, Color blindness, Fragile X
-If mom is carrier: 50% of sons will have disorder and 50% of daughters wil be a carrier
-If a male is affected: none of the sons will be a carrier or affected and females will be carriers |
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Term
| Types of Chromosomal Abnormalities |
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Definition
-Constitutional: Present in every cell or in most cells
-Acquires (Somatic): Present in only certain cells or tissues (Cancer)
-Numerical: Too many/Too few chromosomes
-Aneuploidy: One or more extra chromosomes (common in women over 40)
-Partial Deletions/Duplications: DiGeorge Syndrome is an example; missing portion of the q of the chromosom |
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Term
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Definition
-Often a DeNovo or new event
-parents may be a balanced (appear normal) carrier or even have the condition
-Must determine to provide accurate recurrence risk |
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Term
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Definition
-EX: CF, Marfan, Hereditary breast or ovarian cancer
-Follow patterns of inheritance
-Can be De Novo or inherited |
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Term
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Definition
-Very rare
-Change in a DNA sequence
-Results from DNA copying mistakes, exposure to ionizing radiation, exposure to matgens, infxn by virus
-Germ line mutations occur in the eggs and sperm (can pass on)
-Somatic mutations occur in body cells (not passed) |
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Term
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Definition
-Involves one of two or more variants of a particular DNA sequence
-Most common type involves variation at a single base pair
-Can also be much larger in size and involve long stretches of DNA (SNP)
-SNPs correlate with Dz, drug response and other phenotypes |
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Term
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Definition
-Genetic and Environmental components
-EX: heart defects, spina bifida
-Inheritance risk is almost impossible to nail down
-1st degree relatives with greatest risk |
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Term
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Definition
-A trait in which the same genotype may produce phenotypes of varying severity or expression even with families
-EX: neurofibromatosis |
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Term
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Definition
-The probability of expressing a phenotype, given that an individual has inherited a predisposing gene
-EX: Familial Adenomatous Polyposis (FAP< Hereditary Breast and Ovarian Cancer Syndrome (HBOC) |
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Term
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Definition
-A single disorder, trait, or pattern of traits caused by different mutations within a gene
-EX: CF has over 1000 different mutations that alter the protein |
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Term
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Definition
-A single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci
-EX: Hereditary Non-polyposis Colorectal Cancer (HNPCC/Lynch Syndrome) has multiple genes that cause same phenotype |
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Term
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Definition
-The post-fertilization occurrence of two or more cell lines with different genetic of chromosomal constitutions within a single individual or tissue
-Gonadal Mosaicism: more than one cell type in gonads and may not be detected in other tissues
-Sex Limited: phenotype that is limited in one gender (Male pattern baldness, ovarian cancer in HBOC)
-De Novo: new mutation in individual that was not in the previous generation (Duchenne and Becker MD) |
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Term
| Non-Genetic Limiting Factors of Family Hx |
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Definition
-Incorrect info
-Small families
-False paternity
-Gamete donors |
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Term
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Definition
-Existing Family Hx
-Presence of concerning symptoms: Birth defect, consanguinity, thnicity, pregnancy losses
-Advanced maternal age
-Medication exposures |
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Term
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Definition
-Existing family Hx
-Presence of concerning symptoms: birth defect, developmental delay, dysmorphic features, unique feature, unexplained connections, consanguinity/ethnicity, behavioral features, sensory loss
-Cluse on PE: anomaly or developmental delay; two or more minor anomalies (clinodactaly, low set ears); Major anomaly (heart defect, cleft lip/palate, spina bifida) |
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Term
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Definition
-Early onset cancer (<50); Multiple cancers (>1 primary)
-Family hx
-Unusual cancers (adrenocortical tumor, pheo)
-Related cancers
-Striking features (bilateral breast cancer, males with breast cancer)
-Known mutation |
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Term
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Definition
Lat onset condition (ataxias, MD, Huntington's, Polycystic renal dz, thrombophilia, cardiac arrhythmias, Alzheimer's)
-Transition of care
-Changes in symptoms
-Children at risk
-Symptoms of adulthood: Marfan |
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Term
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Definition
-Family Hx
-Multiple miscarriage
-Reproductive or testing options
-Preimplantation Genetic Dx |
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Term
| What are overall clues to referral? |
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Definition
-Unique or multiple features
-Dysmorphic features of delays
-Family hx
-Questions about genetic testing, recurrence risks, family planning
-Known Dx
-Early onset
-New symptoms |
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Term
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Definition
-These are rare symptoms
-Isolated vs syndromic
-Inheritance pattern is important
-Genetics is a family affair
-New testing or research options
-Unique needs for support |
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Term
| Down Syndrome: Trisomy 21 |
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Definition
CHROMOSOMAL
-Due to nondisjunction
-Males and females
-Features: ID, heart defects, short stature, hearing loss, dysmorphic, poor muscle tone, hypothyroidism, celiac dz, Alzheimers |
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Term
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Definition
CHROMOSOMAL
-Lifespan limited
-Median survival 7 days
-About 10% live past 1 yr
-Can be a result of a balanced 13:14 translocation in parents
-Characteristics: Holoprosencephal; hypotelorism sometimes cyclopia; retinal dysplasia and colobomata; Cardiac defects in 80%; Polydactyly; Scalp defects; other multiple system involvement
-Cleft lip, clenched hand, small head, crumpled ears |
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Term
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Definition
CHROMOSOMAL
-More males than females
-Shortened life expectancy (1/2 die in first month)
-Characteristics: small for age, short sternum, clenched hand
-Multiple organ system involvement
-Cardiovascular: VSD, ASD, PDA
-Neuro: weak, polyhydramniosis, hypertonic
-GI: TE fistula
-Other findings: clenched hands, prominent occiput, malformed ears, shield chest and wide set nipples |
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Term
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Definition
SEX CHROMOSOM ABNORMALITY
-Monosomy X
-Due to nondisjxn
-Females only
-Features: Heart defects, short stature, infertility/amenhorrhea, kidney problems, webbed neck, normal intelligence, lymphedema, nevi, low hairling, small fingernails, widely spaced nipples |
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Term
| Klinefelter Syndrome (XXY) |
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Definition
SEX CHROMOSOM ABNORMALITY
-Nondisjxn
-Infertility (azoospermia or olidospermia)
-Small, firm testes
-Gynecomastia
-Tall, slender body habitus with long legs and shorter torso
-Osteoporosis (in young or middle-aged men)
-Motor delay dysfxn; Speech and language difficulties
-Attention deficits/behavioral
-Learning disabilities; dyslexia or reading dysfxn |
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Term
| VCF: Velocardiofacial Syndrome or DiGeorge Syndrome, 22q11 Deletion |
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Definition
CHROMOSOME DELETION SYNDROMES
-93% De Novo, AD
-Features: Heart defects, clefting, learning delays, psychiatric illness, immunodeficiency
-Other S&S of DiGeorge: Congenital heart dz, palatal abnormalities, hypocalcemia, immune deficiency, learning difficulties, characteristic facial features |
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Term
| Wolf-Hirschorn, 4p-Deletion |
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Definition
CHROMOSOME DELETION SYNDROMES
-"Greek Helmet" face and nasal bridge
-Hypertelorism
-Downturned mouth
-Scalp defects
-Failure to thrive |
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Term
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Definition
CHROMOSOME DELETION SYNDROMES
-15q duplication
-Typically De Novo
-Features: Hypotonia, dysmorphic, poor growth, developmental delays, seizures, autism |
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Term
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Definition
AUTOSOMAL DOMINANT DISORDERS
-6 or more cafe au lait macules over 5mm in greatest diameter in prepubertal individuals and over 15mm in greatest diameter in postpubertal individuals
-2 or more neurofibromas of any type or one plexiform neurofibroma
-Freckling in the axillary or inguinal regions
-Optic glioma
-Two or more Lisch nodules (iris hamartomas)
-A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis
-1st degree relative with NF1 as defined by the above criteria |
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Term
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Definition
AUTOSOMAL DOMINANT DISORDERS
-Clinical: Skeletal (habitus, pectus excavatum/carinatum, scoliosis, reduced elbow extension); lens dislocation; Cardiovascular (aortic root dilation, mitral valve prolapse)
-Skin striae, spontaneous PTX, dural ectasia |
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Term
| Hereditary Breast and Ovarian Cancer (HBOC) Syndrome |
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Definition
AUTOSOMAL DOMINANT DISORDERS
-Males can pass the gene on to their daughters
-Not all women that carry the gene will develop cancer
-Breast cancer <50, ovarian cancer at any age, two or more breast primary or bilateral cancers, Male breast cancer any age |
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Term
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Definition
AUTOSOMAL RECESSIVE CASES
Characterized by: Chronic pulmonary dz; GI/nutritional abnormalities; Frequent illness/infxn; obstructive azoospermia; failure to thrive
-Carrier screening
->1000 mutations
-Delta F508 accounts for 70% of mutations in Caucasians |
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Term
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Definition
AUTOSOMAL RECESSIVE CASES
-Normal HvA, most common traits, Hb S and Hb C
-1/12 AA are a carrier for SS (AS)
-S&S: anemia, pain crisis, vision loss, ulcers, stroke, infxn, delayed growth/puberty
-Other types of hemoglobinopathies: 1% of AA have Hb C trait (AC) |
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Term
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Definition
AUTOSOMAL RECESSIVE CASES
-In an untreated state is associated with plasma Phe concentrations >1000 and a dietary Phe tolerance of <500
-PKU associated with a high risk of severely impaired cognitive development
-Newborn screening
-Microcephaly, epilepsy, severe intellectual disability, and behavior problems
-Dietary restriction especially during childhood can drastically reduce the developmental and cognitive delays
-Maternal PKU |
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Term
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Definition
EXPANSION/REPEAT DISORDERS
-Most common cases of mental retardation
-Phenotype: tall early then short, macrocephaly
-Distinct facial findings: Long face, prominent chin and ears
-Hypotonia, hypermobility (small joint)
-Smooth skin
-Large testicles (post puberty)
-Autistic like behavior, intellectual disability, seizures
-Carier females with risk for premature ovarian failure and carrier males with adult onset ataxia |
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