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Genetic Disorders (Disorders of *Sexual Development (dropped image link…

- - - - Meiosis 1 vs 2 Non-disjunction
        
        Meiosis 1 = disjunction of HOMOLOGOUS chromosomes
        --> homologous = different chromosomes
        
        Meiosis 2 = disjunction of SISTER chromatids
        --> sister chromatid = copy of the SAME chromosome
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
  - - - Clinical Case
      - Notes:
        
        showing here that spin bifida is a complex inheritance pattern
        --> Multifactorial Inheritance
- - - - Clinical Case:
      - Notes:
        
        keys to Bruton/X-linked Agammaglobulinemia are that the patient has:
        
        recurrent infections
        --> suggests there is a possible genetic immunosupression
        
        absent cytosolic tyrosine kinase messaging molecules
        
        X-linked Agammaglobulinemia has B cells that don't mature and ever leave the bone marrow to go to the thymus
        --> recall that B cells are CD19+ and CD20+
    - - Clinical Case:
      - Notes:
        
        keys to Bruton/X-linked Agammaglobulinemia are that the patient has:
        
        recurrent infections
        --> suggests there is a possible genetic immunosupression
        
        absent cytosolic tyrosine kinase messaging molecules
        
        X-linked Agammaglobulinemia has B cells that don't mature and ever leave the bone marrow to go to the thymus
        --> recall that B cells are CD19+ and CD20+
  - - - CURIOUS GEORGE PHAROH MONKEYS WHO are using their 3 and 4 PHAROH FORKS to try and CATCH 22 the HYPOCALCEMIA COW who stole their THYMIC TURKEY LEG on the PLATE and BROKE their TETANIS TITANIC TOY
      - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        DiGeorge Hypothymus Syndrome case 2
        
        Case example:
        
        Notes:
        
        note that DiGeorge Syndrome here presented with the classic low set ears and cleft palate
        
        note that DiGeorge has hypocalcemia and hypothymus
        --> they present with abnormal muscle movements and seizures due to this
        
        DiGeorge Syndrome
        
        T cell deficiency
        
        absent / hypoplastic thymus
        
        normal B cells
        
        DiGeorge is the CATCH 22 --> CATCH all 3 kinds of bugs!
        C = conotruncal cardiac defects (tetralogy of Fallot)
        A = abnormal facies
        T = T cell deficiency / thymus absent or hypoplastic
        C = Cleft palate (or other craniofacial deformities)
        H = hypoparathyroidism / hypocalcemia
        --> think thymus is absent and also the parathyroid
        --> causes hypocalcemia (no PTH)
        3 = CD3 counts are lower due to low T cells (CD3+)
        --> more prone to all infections (bacteria, fungal, viral)
        
        Genetic deletion on chromosome 21 in DiGeorge Syndrome:
        
        DiGeorge syndrome is caused by a heterozygous deletion of part of the long arm (q) of chromosome 22, region 1, band 1, sub-band 2 (22q11.2).
        
        note the chromosome nomenclature goes:
        --> chromosome (#)(p/q = short/long arm)(region on chromosome)(band)(sub-band)
        
        Notes:
        
        DiGeorge Syndrome is a T cell deficiency genetic disorder due to an absent or hypoplastic thymus
        
        T cell deficiency in DiG Syndrome comes from a gene deletion on chromosome
        
        recall that CD = cluster of differentiation re the specific antigens for the different lymphocytes
        
        B cells (humoral immunity / antibodies)
        
        CD20+ are B lymphocyte antigens (these are the ones affected in HIV)
        --> think of the tv station "WB 20" --> B cells have CD20+ antigens
        
        CD3+ are T lymphocyte antigens (these are the ones affected in DiGeorge Syndrome)
        --> think "tylenol 3s = T3s" --> T cells have CD3+ antigens
      - Pathophys of Di George
        
        micro deletion of chrom 22.11
        
        failure of the neural crests cells to migrate to the 3rd and 4th pharyngeal pouches
        --> 3/4 puches make the thymus and parathyroid gland
        --> this causes the thymus and t cell dysfunction and hypocaclemia from the paraT loss
        
        note the thyroid is separate and descends from the glossus foreman cecum canal
- - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        X-linked Androgen
        Insensitive Receptors case 1
        
        biological male = 46 X,Y
        
        Case presentation:
        
        Notes:
        
        Androgen insensitivity x-linked syndrome is similar in many ways to Turner's syndrome, though very different
        --> both are X-linked (Turner's is X chromosome monosomy)
        --> both have phenotype of female
        --> both Turner's and Androgen insensitive receptors (x-linked) present with primary ammenorrhea (menarche late = at or after age 16)
        
        phenotype = female, but karyotype os 46 -XY
        --> normal male levels of testosterone, but androgen receptors are insensitive to testosterone and thus male secondary sexual characteristics can't develop
        --> primary male sexual reproductive organs present = testicles (usually located in the lower abdomen / inguinal area)
        --> default mullerian duct --> no penis, female external genitalia with no uterus
        
        excess circulating testosterone that cannot activate androgen receptors
        --> testosterone converted into estradiol
        --> breast formation and other female phenotypical characteristics
  - - - Infertility of Turner's Syndrome
        
        degeneration of the ovaries
        --> don't produce enough estrogen and progesterone to support a pregnancy plus no oocytes that are mature to be fertilized
        
        CAN give birth ONLY with IVF and estrogen and progesterone supplements for endometrial growth
        
        Clinical Cases
        
        Turner's Syndrome case 3
        
        example shows Turner's, even though there is a missing X chromosome
        
        it comes from meotic non-disjunction
        
        Notes:
        -
        
        Clinical Case
        
        Turner's Syndrome example
        
        example shows Turner's is SOMATIC mosaicism, NOT germline
        
        Notes:
        
        note that 2 types of mosaicism are germline and somatic
        
        any case where there is mosaicism in the phenotype of someone, that is somatic mosaicism
        --> even though it is a sexual genetic condition
        
        germline mosaicism ONLY affects the germline in someone and whether they pass it on to their offspring
        
        Clinical Case
        
        Turner's Syndrome case 2
        
        example shows Turner's Syndrome and risk for aortic coarctation --> infant preductal vs adult postductal
        
        Notes:
        
        note that Turner's Syndrome hasrisk for aortic coarctation
        --> infant preductal vs adult postductal
        
        infant ductus arteriosis
        
        adult = ligamnetum arteriosum
        
        need to be able to recognize Aortic coarctation and aortic dissections based on the symptoms present
        
        note also that for coarctations, you differentiate pre or post ductal based on infant vs adult
        --> here it is a child so post ductal
        --> note on pic to the left, the preductal has a patent ductus arteriosus so there is blood getting to the low extremities
        
        this example shows an important presentation for Turner's syndrome
        
        10% of Turners have aortic coarctation and present with hypoxia to the lower exttremities
        -> look out for this
        
        Clinical Case
        
        Turner's Syndrome case 4
        
        example shows Turner's common presentations
        
        coarctation of aorta --> femoral pulses weak
        
        bilateral swelling of the fett and hands
        
        posterior neck mass = cystic hygroma
        
        Notes:
        
        classic presentations here for Turners Syndrome
        
        coarctation of aorta --> femoral pulses weak
        
        bilateral swelling of the fett and hands
        --> this is due to lymphedmea
        --> very common in Turners in early years of life and slowly regresses
        
        posterior neck mass = cystic hygroma
        --> this is a mix of cysts and connective tissue
        
        Clinical Case
        
        Turner's Syndrome case 5
        
        example shows Turner's most common cardiac defect is bicuspid aortic valve
        
        think that Turner's has 2 wide nipples, 2 wide neck side and 2 aortic valves = bicuspid valve
        
        Notes:
        -
        
        Clinical Case
        
        Presentation of Turner's Syndrome
        "AMENNOREA ...WIDE neck, WIDE breasts, SHORT stature, SHORT ovary life"
        
        "SHORT ovary life" = ovaries degenerate
        --> causes the amennorea
        
        It takes many TURNS to become
        Horse track B CHAMPS
        
        B = bicuspid aortic valve
        --> hard to TURN OPEN the aortic valve
        
        C = cystic hygroma/webbed neck
        --> hard to TURN your NECK
        
        H = Horseshoe kidney
        --> your Kidneys TURN to join each other
        
        A = Aortic Coarctation
        --> your Aorta takes a SHARP TURN inward
        
        M = monosomy X
        --> your other X TURNS into an O
        
        P = Primary Amennoria
        --> you never make the TURN towards puberty
        
        S = Streak Ovaries
        --> your Ovaries TURN into streaks
    - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        Klinefelter's Syndrome
        
        47, XXY
        
        also mosacism + 48 XXXY
        
        Clinical Case
        
        Notes:
        
        note the main presentation of Klinefelter's Syndrome is hypoorchidea, dysfunctional Leydig cells which then causes gynecomastea due to higher levels of FSH and LH
        
        some have intellectual disabilites and some do not
        
        note that these patients usually don't present until puberty
        
        note that 47 XXY is the most common karyotype, bute there is also mosaicism
        --> mosaicism = 46 XX / 47 XXY
        --> 48 XXXY
        
        the more chromosomes the more severe the condition
        
        Notes:
        
        Cryptorchidism = failure of the gabernaculum to drop the testes into the scrotum
        
        XLINE FELTER
        
        X = extra X chromosome
        
        L = little testes (cryptoorchidism)
        
        IN = INfertile and INtelectual disability
        
        Elevated X 2 = FSH and LH
        
        F = facial hair loss
        
        E = estrogen high / gynecomastea
        
        L = long limbs
        
        T = tall and slim
        
        Elevated X 2 = FSH and LH
        
        R = rage/aggressive
        
        Calvine KLINE FELTER FASHION SHOW
        
        MRS LADY BUG = fashion queen was there
        --> abnormal leydig function
        --> high FSH and LH
        --> high estrogen
        
        school bus watching = mental retardation
  - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        *Fragile X Syndrome
        
        most common cause of mental retardation
        
        Notes:
        
        fragile X syndrome is the most common cause of mental retardation
        
        classic clinical features are:
        
        mental retardation
        
        large prominant forehead
        
        large ears and long face
        
        macroorchidism
        --> orchi referring to testicles
        
        Clinical case:
      - F = face is long
        
        R = repeats in FMR gene CGG (=chin and GIANT GONADS)
        
        A = autism and ADHD
        
        G = Giant gonads (testes)
        
        I = intelectual disability (most common cause)
        
        L = large hands and feet
        
        E = ears are long
        
        X = Xtensible joints and X linked dominant
        --> reason why most common
- - - - Notes:
        
        Alpha-thalassemia (causes --> hypochromic microcytic anemia) is seen in southeast Asian populations (Thailand here)
        
        adult Hb
        --> 2 x alpha globin protein chains
        --> 2 x beta globin protein chains
        
        fetal Hb
        --> 2 x alpha globin protein chains
        --> 2 x gamma globin protein chains
        
        gamma globin protein chains have a much higher affinity for oxygen, so in severe Alpha-thalassemia, there are defective alpha Hb, so the body compensates by making 4 gamma-Hb
        --> these 4 gamma chains are too high in O2-affinity
        --> they cannot drop off O2 to tissues and you get severe hypoxia and death
      - Clinical Case:
- - - - Marfan Presentation:
        
        flat feet
        
        pectis carinatumm / pectis excavatum
        
        arachnodactyly
        
        high arm to height ratio
        
        tall and thin
        
        longer legs than torso
        
        affects skeleton, eyes and CVS
        --> scoliosis / kyphosis
        --> blurred vision
        --> heart problems
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        Marfans syndrome and CVS complications
        
        2 most common CVS problems in Marfans
        
        NOtes
        
        75% of Marfans have aortic aneurisms
        --> lead to aortic dissection = most common cause of death
        
        mitral valve prolapse
        --> mitral valve regurgitation
        
        Case presentation:
        
        *Fibrillin in Marfans
        -
      - MARFANS :
        
        M = MVP
        
        A = AR (A regurge), AR (ARachnodactyly)
        --> (ARACHNO - dactyly = "spider fingers" vs plain Dactyly = sausage fingers)
        
        R = retinal detachment
        --> (lens cords have fibrillin/elastin)
        
        F = fibrillin-1 (ligaments and blood vessels)
        
        A = AN = aoritc ANeurism
        
        N = Negative Nitroprusside
        --> (differentiates HOMOCYsteinuria whihc has marfan in it)
        
        S = subluxated lens (=ectopia lentus)
        
        Subluxation = ectopia lentus of the lens
        
        the lens is displaced in the eye, but still in the capsule (floating)
  - - - Notes:
        
        Q: what is the probability that her son marked with a P will get the disease?
        --> solution = 50%
        
        note that in Duchene's MD there is normal development until about age 4, normal crawling and walking, etc.
        
        then the child starts to have proximal lg weakness, then distal and also upper extremity muscle weakness
        
        Duchenes MD is an X-linked recessive disorder
        -->thus it mostly affects men and women are normally carriers, since they have one affect X and one normal
        
        note that it matters whether the parent carrier is male or female
        
        "walking up your legs like a RECESSIVE DUCHE!!"
        --> Duchenne's is x-linked recessivve
        --> presents clinically with 4 year old boys walking up their own legs to get up
        --> this is called Gowers sign
      - Case presentation:
- - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        Trisomy 21 = Down's Syndrome case 2
        
        Downs have a high incidence of umbilical hernia
        
        they can happen without Downs though --> Ella and Cecilia
        
        they spontaneously close in first few years
        
        if not closed by age 5 --> operate to close it
        
        Notes:
        
        note that there are 3 causes of Down's Syndrome that all result in Trisomy of chromosome 21
        
        95% of cases are meotic nondisjunctions = meaning one parent's chromosome 21 doesn't disjoin and you get a trisomy
        
        ~ 2% = unblanaced translocations
        
        < 2% = mosaicism
        --> note that the last 2 are very rare, but can still lead to trisomy
        
        Clinical Case
        
        Trisomy 21 = Down's Syndrome case
        
        most common GI defect in Downs is duodenal atresia
        = closure of the Gi tract at the duodenum
        
        present with emesis and classic "double bubble" air in the GI
        --> stomach and duodenum
        
        Notes:
        
        note that on scan Trisomy 21 has increased nuchal transluciency
        --> area down the back of the fetus
        --> not sure what it is?
        
        also on labs it has decrease Alpha fetoprotein = AFP
        
        Clinical Case
        
        Trisomy 21 = Down's Syndrome case 3
        
        Downs is normally trisomy caused by non-disjunction during meiosis
        
        smaller subset are caused by balanced robertsonian translation carriers
        
        Balanced Robertsonian Translocations
        and Acrocentric Chromosomes
        
        Notes:
        
        note that
        
        Clinical Case
        
        Trisomy 21 = Down's Syndrome case 1
        
        Notes:
        
        note that there are 3 causes of Down's Syndrome that all result in Trisomy of chromosome 21
        
        95% of cases are meotic nondisjunctions = meaning one parent's chromosome 21 doesn't disjoin and you get a trisomy
        
        ~ 2% = unblanaced translocations
        
        < 2% = mosaicism
        --> note that the last 2 are very rare, but can still lead to trisomy
        
        Clinical Case
      - Sequalae to Down's Syndrome
        
        ASD in 80% of cases?
        
        acute lymphoblastic leukemia = ALL
        
        most common Cardiac defect in Down's is common AV valve
        
        Downs's Cardiac defects
        
        endocardial cushion defects
        
        most common Cardiac defect in Down's is common AV valve
        --> between both chambers of the heart
      - C = cardiac A/V complete and septal defects (ASD most common)
        
        H = hypotonic / hypoplastic midface
        
        E = epicanthic folds
        
        F = flattened nose
        
        S = Short stature and simean crease
        
        B = brachycephaly (short skull)
        
        U = upslanting palpable fissures
        
        G = GAP 21 = gap in 1st /2nd toe
        
        M = mental retardation
        
        A = atresia (duodenal/anal) and APP gene on chromosome 21 = early AD
        
        P = protruding tongue
        
        Presenting Signs and Symptoms of Down's Syndrome
        
        Lets GET DOWN!!! Night Club for Downs people
        
        Duodenal Atresia Tree = Bouncer of the club
        
        Club closes at midnight = AD early in downs
        --> APC = amyloid precursor protein
        --> APC is on chromosome 21
      - *Diagnosis of Downs
        
        Quad blood screening test for Downs syndrome
        
        AFP
        
        hCG
        
        Estriol (estrogen from babies liver)
        
        Inhibin A
        
        *Quad screening test for Downs
        
        Quad blood screening test for Downs syndrome
        
        Low markers for Downs:
        
        LOW AFP
        
        LOW Estriol (estrogen from babies liver)
        
        Raised = placenta compensation markers for Downs:
        
        hCG
        
        Inhibin A
  - - - Patau MNeumonics
        
        pataeu syndrome = PUBERTY time
        
        PUBERTY PADDLE PATEAU HALL MONITOR BABY who wear his HOLOPROSENCEPHALY HALO for being so perfect and ROCKS back and forth on his ROCKER BOTTOM FEET and POLYCYSTIC KIDNEYS
        
        PUBERTY PATEAU the HALL MONITOR with PADDLES
        
        PUBERTY PATEAU PADDLE HALL MONITOR notices some BROKEN CLEFT PLATES and VASEs with DEFECTS in them because TRISOMY 13 ran them over with his TRYSOMY
        
        HALL MONITOR PADDLE PATEAU hits him in his MICROENCEPHALY small head
        
        PUBERTY HALL MONITOR PADDLE PATEAU then paddles POLLY DACTYLY who is TEXTING when she should have been studying her RETARDED TAR BOOK
  - - - Edwards Scissor Hand = EDWARDS Syndrome = Trisomy 18
        "EDWARD Scissor Hand president slogan = Make America Kids Again"
        
        E = elongate skull of his BUSH
        
        D = Digits overlapping
        --> his Scissor hands
        
        W = VSD
        --> V in his scissor hands
      - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
        
        Trisomy 18 = Edward's Syndrome
        
        Notes:
        
        remember the EDWARD mnemonic for trisomy 18
        E = ELONGATED occiput
        D = DIGITS 2 and 5 extend over the other
        W = / V --> VSD = ventricular septal defect Cardiac problem
        A = APNEA = cause of death usually
        R = ROCKER-bottom feet
        D = disability and dysplastic ears = low set
        
        Clinical Case
- - - - *Prader Willi Syndrome
        and Angelman Syndrome
        
        imprinting of chromosome 15
        --> either loss of the imprinting from one parent or loss of entire imprinting gene caused by uniparental disomy
        
        *Prader Willi Syndrome
        
        imprinting of chromosome 15
        
        inherited alleles ONLY from MOM
        
        either microdeletion from father
        
        or complete loss of father gene from uniparental disomy from mom
        
        *Angelman Syndrome
        
        imprinting of chromosome 15
        
        "DADDYs little ANGEL..."
        --> inherited alleles ONLY from DAD
        
        either microdeletion from mother
        
        or complete loss of mother gene from uniparental disomy from dad
- - - - Notes
        
        note that auto recess is always carrier probability x 1/2
      - Case example:
    - - *Homocystinuria
        
        see metabolism map
        
        high homocysteine in urine
        
        recall HOBO peter patrick
        --> living in the Cystern
        --> has MARFANS syndrome
        --> with HOMOCY + OCCULAR problems
        
        recall HOBO peter patrick PYRIDIMINE and the Methionine VB12 THF folate cycle
        --> can't convert homocysteine --> cysteine and disrupts the whole methionine pathway
        --> can't make sulfur containing AA's
        --> needed for collagen 1 in MARFANs
        
        HOMOCYsteine
        
        H = high homocysteine in urine
        
        O = occular problems
        
        M = marfans (kyphosis and CVS with it)
        
        O = osteoporosis
        
        C = CVS problems
        
        Y = kYphosis (from the marfans)
        
        see metabolism map
        
        *CF = cystic fibrosis
        
        mutation in CFTR Cl- ion protein channel
        --> most CFTR can't fold and get degraded before reaching the surface
        
        CF in eccrine sweat glands
        --> in resp pumps the cl- out of sweat ducts and back into the cells
        --> again the ENaC get inhibited
        --> high salt in sweat
        
        CF in lungs and pancreaas
        --> in resp pumps the cl- out
        --> CFTR inhibits the Na+ ENaC also
        --> get dry mucus in lungs = viscous
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        CF = Cystic Fibrosis example
        
        shows if someone with NO disease present and heterozygous auto recessive parents
        --> 2/3 chance of being a carrier
        --> 1/3 chance of passing 1 mutated allele on
        
        Notes
        
        note that since he has a sibling with CF, and her parents have no disease
        --> skipped generation
        --> auto recessive
        --> means her parents are heterozygous
        
        draw a punnett square
        --> 4 choices, but patient doesn't have the disease so only 3
        
        of these 3 2 of them are carriers
        --> 2/3 chance of being a carrier
        
        note that crucial step now is to multiply by 2 since if you assume she has 2/3 of being a carrier, she now has to actually pass one of those one
        
        Case example:
    - - Note:
        
        for autosomal recessive someone with NO disease present and heterozygous auto recessive parents
        --> 2/3 chance of being a carrier
        --> 1/3 chance of passing 1 mutated allele on
  - - - *X-linked recessive disorders
        
        G6PD deficiency (HMP Shunt)
        
        WAS = Wiskott-Aldrich Syndrome
        --> WASp mutation
        --> WATER triad
        
        *WAS = Wiskott-Aldrich Syndrome
        
        WASp mutation
        
        WA-TER triad
        --> thrombocytopenia
        --> Eczema
        --> recurrent infections (immunodeficient)
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
  - - - *pleiotropy = "ploidy of phenotropes"
        
        multiple phenotypes from one gene
        --> ex: homocysteinuria (HOMOCY symptoms) = all very different systems and proteins but from the same gene
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
      - *Linkage disequilibrium
        
        the frequency of 2 separate genes/alleles on the same chromosome coming together in the same HAPLOID gamete cell is
        --> GREATER than expected
        
        Example:
        
        always take the frequency of the two alleles
        --> p = 0.2 and q = 0.3
        --> multiply them = 0.2 x 0.3 = 0.06
        
        expected frequency of the 2 seaparate genes together = 0.06
        --> but in this example the ACTUAL frequency of them together = 0.02
        --> much higher than the 0.06 expected
        --> thus LINKAGE DISEQUILLIBRIUM
        
        Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
      - *Polygenic Inheritance
        
        "POLY GENES" determine 1 thing
        
        "AA 8EIGHTS Ball Diseases"
        --> AA = Androgenic Alopecia (most common form of male balding and also done by polygenic)
        --> Ball = WB 20 chromosome
        
        *Androgenic Alopecia
        
        "POLY GENES" determine 1 thing
        
        "AA 8EIGHTS Ball Diseases"
        
        AA = Androgenic Alopecia (most common form of male balding and also done by polygenic)
        --> Ball = WB 20 chromosome for AA
        --> also X and Y chromosomes
        --> reason why you have variable expressivity with males vs females
- - - - Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that
      - Mitochondrial disorder
        
        blotchy red muscle fibres on stain
        
        Clinical Case
- - - - *Achondroplasia
        (Dwarfism)
        
        normal trunk of the body with shorter limbs and extremities
        
        autosomal dominant
        --> BUT 80% are actually sporadic mutations and only 20% are hereditary
        
        mutation in the FGTR gene = fibroblast growth factor receptor
        
        "Tiaran Lannister is A CON MAN and the Hounds funny GFR" = "CON MAN" = achondroplasia
        --> Peter Dinklage has achondroplasia
        
        for achondroplasia think of "Hounds funny GFR and her NEEDLE"
        --> "GFR " = funny little GIRLFRIEND
        --> "stick them with the POINTY END"
        --> Terian = point mutation in FGFR
        --> MARFANS in contrast has the "TGFR = transforming" mutation for fibrillin-1 for estin scaffolding
        
        Pathophys - Achondroplasia
        
        Abnormal Endochondrial Bone growth in Achondroplasia
        
        normal membranous bone growth
        --> facial bones + clavicle
        --> they have a large head and large clavicle
        
        Clinical Cases
        
        Clinical Case
        
        Notes:
        
        note that
        
        Clinical Case
        
        *Achondroplasia
        (cases)
        -
        
        Clinical Case:
        
        Notes:
        
        to the left is Peter Dinklage, who has achondroplasia and FGFR1 gene mutation
        
        achondroplasia = means "without cartilage growth"
        
        achondroplasia is not the only type of condition causing dwarfism (or little people), but it does make up 80% of the cases of dawrfism
        
        interesting that 90% of achondroplasia actually comes from de novo genetic defects in the germline FGFR1 gene
        --> only 10% are inherited from parents with mutated FGFR1 gene
        --> this is even surprising since achondroplasia is also autosomal dominant
        
        note that even though most achondroplasia cases are de novo spontaneous genetic mutations, if you have the condition you are highly likely to pass it on to your children
        --> homozygous achondroplasia is usually not compatable with life past the first month of life
        
        brachydactyly
        --> brachy- = short; brady- = slow
        
        -dactyly = referring to digits (fingers and toes)
        
        midface hypoplasia
        --> the scrunching up of the midline of the face in achondroplasia
        
        rhizomelia = shortened proximal limbs
        --> both upper and lower limbs
        
        "trident hands"
        --> space between the 3rd and 4th digits in achondroplasia
        
        Frontal bossing is a medical term used to describe a
        --> prominent, protruding forehead that’s also often associated with a heavy brow ridge
        --> think of Tyron Lannistor as the BOSS --> frontal bossing
        
        patients with achondroplasia have increased risk of spinal stenosis
      - *Neurocutaneous genetic disorders
        --> neuro and skin signs together
        
        Neurofibromatosis
        --> types 1 and 2
        
        VHL = Von-Hippel-Lindau Syndrome
        
        Tuberus sclerosis
        
        Sterge-Weber syndrome
        
        *VHL = Von Hippel-Lindau Disease
        
        mutation in VHL
        - "the VON HARP"
        
        VONT trap dominant kid plays the HARP
        
        "the VON HARP"
        
        VONT trap dominant kid plays the HARP
        --> can't stand because of RP (renal and adrenal problems)
        
        dominant kid = autosomal dominant
        
        H = hemangioblastoma
        
        A = angiomatosis
        
        R = renal cell carcinoma (RCC bilateral)
        
        P = pheochromocytosis
        --> RCC and pheochromocytosis are the VON trap kids RP reanal and adrenal problems
        
        2 more items...
        
        *NFM = Neurofibromatosis
        
        type 1 and 2
        
        Neurofibromatosis (type 1)
        
        "CAFE SPOT" --> eyes, arm pits, fibro back and BOWed Tibias
        
        Clinical Cases
        
        2 more items...
        
        4 more items...
        
        Neurofibromatosis (type 2)
      - *FHH = Familial Hypocalciuric Hypercalcemia
        
        mutation in CaSRs = calcium sensing receptors
        
        CaSRs = G protein receptors
- - - - Clinical Cases
        
        Clinical Case
        
        Clinical Case
        
        Notes:
        
        note that