Genetics Flashcards
Brachial cyst vs thyroglossal duct cyst
Thyroglossal duct cyst– midline or near midline (usually moves the tongue movement/swallowing
Brachial cleft cyst– can be anywhere along the neck (more lateral) and even more preauricular, may have an overlying pore or sinus; marsupilization if becomes secondarily infected
Waardenburg Syndrome and mode of inheritance?
Autosomal dominant White forelock of hair Albinism (including ocular) Heterochromia Deafness
Apert Syndrome and mode of inheritance?
Autosomal dominant Early cranial suture closure (long head) Bilateral syndactyly Choanal atresia Cleft palate
Head shaped like “A PEAR” with duck-like hands; or think of daffy-duck?
Nail Patella Syndrome
Mode of inheritance: Autosomal dominant Abnormal nails (pitting, ridging, splitting) Abnormal patella (small, absent, irregular) Elbow deformities as well (kinda like the patella of the hands)
Noonan’s Syndrome
Autosomal dominant
Webbed neck, low set ears
HOCM/ pulmonic stenosis (subvalvular)
Pectus excavatum
Achondroplasia
Autosomal dominant
Frontal bossing/macrocephaly
Normal sized torso with short arms and legs
Sudden death cause: compression of the cervicomedullary junction (head is too big for body–memory aid)
Genu varum deformity (bowed legs)
Trident-like fingers– because hand is so small, fingers have to spread far apart from each other like a trident
Peutz-Jeghers Syndrome
Autosomal dominant AKA hereditary intestinal polyposis Hamartomatous GI polyps Hyperpigmented macules on the lip/oral mucosa Life-time risk of cancer is increased.
Gardner Syndrome
Autosomal dominant
AKA familial adenomatous polyposis
Premalignant polyps throughout the intestine but whole lot of other extras
Extra teeth and tumors in other parts of the body–including bone tumors– needs to be resected
Gardner with extra teeth with all kinds of overGROWTH all over him
Retinoblastoma
Autosomal dominant– although high rate of spontaneous mutations, don’t discount just because there is no family history
Increased risk of osteosarcoma
Leukocoria
von Willebrand Factor deficiency mode of inheritance?
Autosomal dominant
Acute Intermittent Porphyria mode of inheritance and disease symptoms?
Autosomal dominant
Accumulation of metabolite of heme synthesis in the cytoplasm of cells
Abdominal pain, confusion, weakness, photosensitivity
Triggers– infections, hypoglycemia, seizure/sulfa medications
Treat with D10 infusion and stop offending agents.
Retinitis pigmentosa
Retinal dystrophy leading to blindness
Multiple modes of inheritance
Tuberous Sclerosis mode of inheritance?
Autosomal dominant
Mnemonic for autosomal recessive disorders?
PAT HAS WACK GAS in the BACK SEAT of the automobile
Phenylketonuria (PKU) Alpha-1- Antitrypsin Tay-Sachs Hurler's syndrome Ataxia Telangiectasia Sickle cell disease and Thalassemias Wilson's disease Alpers Syndrome Cystic Fibrosis Kartagener's Syndrome Galactosemia A- repeat A's from above S- repeat S's from above
BACK SEAT of automobile– autosomal recessive
Johanson-Blizzard Syndrome
Autosomal recessive
Pancreatic insufficiency
Hypoplasia of nostrils
Scarlett Johansson is holding her pancreas and cannot smell?
X-linked dominant disorders will present in what population of patients?
100% daughters of an affected male, does not present in sons (because gets Y chromosome from father)
Familial Hypophosphatemic Rickets is also known as? Mode of inheritance?
Vitamin D Resistant Rickets
X-linked dominant
Aicardi syndrome
X-linked dominant
Missing corpus callosum
Mental retardation
Infantile spasms, epilepsy
Imagine Cardi-B missing her corpus callosum because she is dumb– memory aid
Alport Syndrome
X-linked dominant
Renal disease– hematuria and eventually ESRD
Bilateral sensorineural hearing loss
Vision problems
Fragile X Syndrome
X-linked dominant
Trinucleotide repeat disorder
Most common cause of inherited MR
Social awkwardness, macro-orchidism, large ears, prominent jaw
Chronic Granulomatous Disease
X-linked recessive
Child is diagnosed with Serratia
Other common bugs (Aspergillus, Candida, E. coli, staph- catalase positive organisms)
Nitroblue Tetrazolium or Dihydrorhodamine testing
Several kinds of abscesses, osteomyelitis
Duchenne Muscular Dystrophy
X-linked recessive
Deficiency of the dystropin gene
Poor cough, frequent pneumonias
Weak respiratory muscles– respiratory failure
Gower’s maneuver
CK for screening
Genetic testing for confirmation– if unknown, muscle biopsy
MOP can have elevated CK if she is a carrier and be asymptomatic
G6PD deficiency
X-linked recessive
Jaundice, dark urine, hemolytic anemia
Exposure to Bactrim, fava beans, cipro, nitrofurantoin
Mediterranean and African American descent
Heinz bodies–denatured hemoglobin
Check G6PD levels few weeks after acute phase– false negative
Hemophilia A and Hemophilia B
X-linked recessive
Factor VIII and IX deficiencies respectively
PTT is increased
Deep bleeds (into joints/muscles)
Hunter’s Syndrome mode of inheritance?
X-linked recessive
Ornithine Transcarbamylase deficiency mode of inheritance?
X-linked recessive
Androgen Insensitivity?
X-linked recessive
Testicular feminization (no male external genitalia even though testes/gonads are present)
Testes may be found in the inguinal canal
Blind ending vagina
Lacks of female reproductive organs (ovaries, uterus)
May have breasts and no pubic hair?
Wiskott Aldrich Syndrome?
X-linked recessive Both T and B cell problems Thrombocytopenia or small sized thrombocytes Recurrent infections Eczema IgM low, IgA high Treatment: BMT
Name the disorder: round face, almond shaped eyes, MR, upslanting palpebral fissures, sandle-toe deformity, simian crease, flattened nasal bridge, macroglossia
Down’s Syndrome
Name the disorder: atlanto-axial instability, AV canal or VSD heart defect, clinodactyly (incurved pinky finger)
Down’s Syndrome
True or False: both males and females with Down’s Syndrome are infertile.
False. Males with Down’s Syndrome are typically infertile, while females with Down’s are not.
Brushfield spots vs Stellate eyes
Brushfield spots- associated with Down’s syndrome, around the periphery of the iris
Stellate eyes- Williams Syndrome involves the entire eyes, bursting from the center
Trisomy 21 Down’s– risk of recurrence in future pregnancies? What would you see on karyotype of parents?
Mother’s age related risk + 1%
Normal parental karyotype, non-dysjunction occurs during miosis
Translocation Down’s workup
Need parental karyotype to determine risk of future recurrent pregnancies with Down’s
Chromosome 21 translocated onto chromosome 14 or another chromosome 21
Translocation Down’s risk of recurrence in future pregnancies?
If t(21q;21q)– 100% risk of recurrence, because they only have that copy of chromosome 21 to give
If t(21q;14q)–
Mom is the carrier: 10-15% risk of recurrence
Dad is the carrier: 5% risk of recurrence
Presentation of atlantoaxial instability in a down’s syndrome patient?
Brisk reflexes, gait disturbances or other neurological symptoms in a Down’s Syndrome kid
Obtain an X-ray/MRI (preferred) in this kid
Name the disorder and prognosis? Rocker bottom feet Clenched fists with overlapping fingers Horseshoe kidneys Small jaw (micrognathia) Pectus excavatum
Trisomy 18 or Edward’s Syndrome
Usually die in utero or survive to 1 years of age
Name the disorder and prognosis? Punched out scalp lesions Low set ears Cystic kidneys Cleft lip/palate Micro-ophthalmia, microcephaly Polydactyly
Trisomy 13 or Patau’s Syndrome
Poor prognosis, usually survive to 6 months old
Bifid uvula may be an outward sign of what hidden issue?
Submucosal cleft palate
May also have difficulty hearing due to affected tympanic membrane movement.
Name the disorder: Cocktail party personality Elfin face Low and flat nasal bridge Upturned nose Wide spaced teeth Supravalvular aortic stenosis Peripheral pulmonic stenosis
Williams’s syndrome
Hypercalcemia
Holt Oram Syndrome
Upper limbs and cardiac abnormalities
Upper limbs- hypoplastic radius and thumb OR triple jointed thumb
Cardiac abnormalities- ASD/VSD
Cri-du-chat syndrome, genetic locus?
5p deletion syndrome or 5p minus syndrome High-pitched cry Developmental delay Wide-set eyes High palate
Crouzon Syndrome
Early suture closure (craniosynostosis)
Proptosis
Frontal bossing
Cleft lip/palate
Similar to Apert Syndrome– EXCEPT LACK OF SYNDACTYLY
Angelman Syndrome, genetic imprinting?
Happy, laughing frequently Puppet gait-- ataxia Delayed milestones Chromosome 15- missing or defective mom's copy, paternal imprinting (behaves like the paternal allele for the gene) Diagnosed by FISH
Father’s angel, daddy’s girl– but can be found in boys and girls
Prader-Willi Syndrome, genetic imprinting?
Hypotonia as a baby, poor feeding Growing up and have an enormous appetite Small phallus Obesity Small hands Almond-shaped eyes Mild retardation Diagnosed by FISH
Absence or dysfunction of the paternal copy; maternal imprinting (behaves like the maternal allele for the gene)
Mama’s boy, feeds him whatever he wants– but can be found in boys and girls
Supravalvular aortic stenosis is associated with which disorder?
Williams Syndrome
Laurence Moon Biedl Syndrome features
Similar to Prader-Willi syndrome but PROGRESSIVE
Replace Laurence with Insurance
Moon– (OoO) makes you think of eyes (retinitis pigmentosa), small brain (progressive CNS disease), and hypogonadism/hypospadias
Beckwith-Wiedemann Syndrome features
Macroglossia, macrosomia (large body) Hemihypertrophy Increased risk of Wilms Tumor Mid-line defects (omphalocele/umbilical hernia) Born with hypoglycemia
Klippel-Trenaunay Syndrome features
AV fistulae
Port-wine stain
Hemihypertrophy (bone, soft tissues)–especially of a unilateral extremity
Hemihypertrophy is found in which disorders?
Beckwith-Wiedemann Syndrome
Klippel-Trenaunay Syndrome
Russell-Silver Syndrome
Proteus Syndrome
Smith-Lemli-Opitz and mode of inheritance?
Autosomal recessive
Cleft palate, 2-3 syndactyly of toes, extra digits
Microcephaly, MR
Underdeveloped genitalia in males/hypospadias
Cardiac defects
Klippel-Feil Syndrome features?
Failure of the cervical vertebrae to clip–> torticollis
Proteus Syndrome features?
Hemihypertrophy
Pierre-Robin Syndrome features?
Triad of cleft palate, micro/retrognathia, and glossoptosis (retraction and falling back of tongue onto posterior palate because of retrognathia). Concern for airway obstruction, especially with laying supine.
High risk for cor pulmonale within the first year of life.
Syndactyly/clinodactyly
CHARGE syndrome?
Coloboma Heart defects Atresia (choanal) Retarded (slowed) growth Genitourinary anomalies Ear anomalies
Leading cause of congenital blindness-deafness.
Cockayne Syndrome features?
Premature aged appearance, photosensitive skin, dwarfism (slowed growth), vision/hearing problems
True or false. The most likely physical manifestation of schwannomas includes bitemporal hemianopsia.
FALSE. Bilateral ACOUSTIC neuromas– hearing impairment is more likely. Bilateral hemianopsia is associated with a pituitary gland or sella turcica tumor.
Name the disorder: facial muscle wasting/atrophy, firm grip with difficulty releasing grip, proximal muscle strength is intact. What is the mode of inheritance of this condition?
Myotonic dystrophy. Autosomal dominant.
Name the disorder: port-wine stain along the V1 distribution of the face. What complications is this child at an increased risk for?
Sturge-Weber syndrome– think of a web of capillaries over the face? Complications- seizures/glaucoma.
Name the disorder: at birth infant identified to have a low-lying hairline, redundant nuchal fold and edema of dorsal hands and feet.
Turner Syndrome
Noonan syndrome is associated with what kind of hematologic condition?
Bleed diathesis– usually factor 11 deficiency/thrombocytopenia; frequent bruising
Wide carrying angle and hyperconvex fingers nails are associated with what disorder?
Turner Syndrome (also known as cubitus valgus)
What are some signs/symptoms of myotubular myopathy in a newborn?
Poor muscle mass (arrest in neonatal muscle maturation), respiratory distress/failure, muscle biopsy shows poorly developed muscle fibers and abnormal nuclei; pharyngeal weakness–> poor swallow–> polyhydramnios
Name the disorder: downward-facing epicanthal folds, eyelid coloboma, hypoplasia of significant portion of facial bones (frontal/malar/etc), normal intelligence, retrognathia, lacking eyelashes on the lower lids, malformed ears, poorly formed sinuses, bilateral conductive hearing loss, cleft lip/palate
Treacher-Collins Syndrome
Name the disorder: frequent infections, loud/harsh holosystolic murmur at the LLSB, hypertelorism, under-developed philtrum, bifid uvula, velopharyngeal insufficiency.
DiGeorge Syndrome
Velopharyngeal insufficiency– soft palate is supposed to block off nasopharynx from oropharynx during speech/swallow but it doesn’t (nasal speech, regurgitation of oral cavity contents into nasopharynx)
Mnemonic CATCH 22
For DiGeorge Syndrome
Cardiac anomalies (ToF, truncus arteriosus, ASD/VSD)
Abnormal facies
Thymic aplasia
Cleft palate/velopharyngeal insufficiency
Hypocalcemia/HypoPTH
22– chromosome 22 microdeletion
Cardiac rhabdomyomas are associated with which syndrome? What neurological manifestations can be seen in this disorder?
Tuberous sclerosis (autosomal dominant). Seizures/infantile spasms.
Name the disorder: notable verbal delay, hand-flapping (easily excitable), tremulous movements of the limbs/ataxia, inappropriately laughing/happy, mouth open with frequent drooling and thrusting of tongue. What chromosome is affected?
Angelman Syndrome (chromosome 15). Paternal imprinting, loss of maternal gene (daddy's girl-- although can be seen in both boys and girls).
Name the disorder: axillary freckling, seizure disorder, T2-weighted brain MRI showing multiple bright spots along brainstem/basal ganglia/cerebellum, multiple hamartomas noted on the iris, cortical thinning of long bones
Neurofibromatosis (autosomal dominant)
Multiple hamartomas– lisch nodules
What does WAGR stand for?
Wilms Tumor
Aniridia
Genitourinary anomalies
Retardation (reduced intellectual abilities)
Name the disorder: before age of 2 years old, irritable infant with tender bones–especially mandible. Radiography reveals hyperostosis of cortical bone.
Caffey syndrome (infantile cortical hyperostosis).
Autosomal dominant with incomplete penetrance.
Usually involves mandible, but can involve any bone.
Usually resolves by age 2 years old.
Name the associated disorder: dome-shaped yellowish brown papules that project from the iris.
Lisch nodules (neurofibromatosis).
Name the disorder: prominent forehead, pointed chin, direct hyperbilirubinemia with paucity of bile ducts, hepatomegaly, butterfly vertebrae
Alagille syndrome
Name the disorder: puffy eyes, full or wide mouth, cocktail party personality.
Williams syndrome
Name the disorder: FTT, long eyelashes, micrognathia, downward turn upper lip, unibrow, hirsuitism
Cornelia de Lange syndrome
Name the syndrome: neonate who presents with hypocalcemic seizures.
DiGeorge syndrome
Name the syndrome: neonate with intracranial hemorrhage, thrombocytopenia and absent radius.
TAR (thrombocytopenia with absent radius) syndrome
There is a 5-15x increased risk of Celiac disease in patients with what genetic disorder?
Down’s Syndrome
Pseudarthrosis/cortical long bone thinning leading to anterolateral bowing of the tibia with pathologic fractures or sphenoid dysplasia is associated with what disorder?
Neurofibromatosis
What is transient leukemia?
Leukemia where blast cell population in the blood exceeds that in the bone marrow, seen in Down’s syndrome. Usually resolves within 3 months or so without intervention. Although increased risk for AML in the future.
Name the disorder: doughy consistency skin, poor wound healing, mitral valve prolapse, easy bruising.
Ehlers-Danlos syndrome.
What is Stickler syndrome?
A group of genetic disorders that affects connective tissue. Tends to be associated with Pierre-Robin sequence.
