Genetics - making cards Flashcards
Liddle Syndrome
HYPERTENSION with HYPOkalemic metabolic ALKAlosis
Asymptomatic Children
Adult onset bloating, nausea and vomitting (HTN/HypoK Sx)
Differential with Hyperaldosteronism conditions (tumours, primary mutation)
Autosomal Dominant (Rr)
Early Onset Gene: uSCNN1B/G
Management: Low NaCl diet and K-sparing Dieuretics
Barter Syndrome
Congenital Furosemide Overdose
Pre-natal Salt Wasting from electrolyte resorption (Renal) Impairment Oligohydramnios (with RDS, pulm. hypoplasia) HYPOcalcemia - osteopenia, cramping, arrhythmia risks HYPERcalciuria - stones HYPOkalemia - muscle cramping/weakness Mild cases are subtle polyuric failure to thrive as well Autosomal Recessive (rr) Gene Types: (1) uSLC12A1, (2) uKCNJ1, (3) uCLCNKB, (4) uBSND or CLCNKA+B
Management: (1) Chronic NSAIDs, (2) K-sparing diurectics, (3) ACEi (4) K and Mg supplementation
Gitelman Syndrome
Congenital Thiazide overdose
LATE onset Salt Wasting from electrolyte resorption (Renal) Impairment HYPOkalemia - muscle cramping/weakness HYPOmagnesemia - muscle cramping/cardiac arrhythmia, paresthesias HYPOCalcemia - cramping, arrhythmia Autosomal Recessive (rr) Gene: uSLC12A3 or uCLCNKB (rare)
Gordon Syndrome
HYPERTENSION with HYPERkalemic metabolic ACIDosis Autosomal Dominant (Rr) Early Onset Gene: uWNK1/4 or uKLHLB or uCOL3
Trisomy 13 - Patau Syndrome
Several congenital anomalies the typically are not compatible with sustained life - those that survive do so because of mosaicism. - IUGR - Cleft Lip/palate, ear malformations, Cutis aplasia - Holoprosencephaly (No forebrain development) - Polydactyly, Rocker-bottom feet - Hypotonia, Clenched Fists, anophthalmia - Renal Malformations and Cryptorchidism - Complex cardiac anomalies Gene: Mosaic distribution of a third chromosome 13
Trisomy 18
Several congenital anomalies the typically are not compatible with sustained life - those that survive do so because of mosaicism. - IUGR - Dolichocephaly, Ext Ear Malf., Microgrnathia, Short palpebral fissures (No typical cleft lip/palate) - Rocker-bottom feet - Hypotonia, Clenched Fists - Renal Malformations and Cryptorchidism - Complex cardiac anomalies Gene: Mosaic distribution of a third chromosome 18
Li Fraumeni Syndrome
Tp53 Mutation
ALL
Adrenocorticalcarcinoma (common)
Choroid plexus carcinoma
Breast Cancer
Neurofibromatosis Type 1
Autosomal Dominant (Rr)
Diagnostic if 2+ Criteria
- ≥ 2 Neurofibromas or a plexiform neurofibroma (Intracranial or large p-nerve sheaths)
- ≥ 6 cafe-au-lait macules (Small or big)
- Diameter > 5 mm prepubertal (>15 postpubertal)
- Axillary or Inguinal Freckling
- Optic glioma
- ≥ 2 iris hamartomas (Lisch nodules)
- Distinctive osseous lesion
- First Degree Relative diagnosed
Neurofibromatosis 2
Beckwith Wiedemann Syndrome
Wilms Tumour-Aniridia-Genitourinary anomalies-Intellectual Disability (WAGR) Syndrome
What is the pathophysiology of Fragile X Syndrome?
CGG Repeats which worsen with each generation
- 5-44 repeats is normal
- 45-54 repeat is a “gray” zone
- 55-200 repeats is Premutation Carrier - Gives Son disease
- > 200 Repeats is Mutation - Has disease
Fragile X Syndrome
Physical Issues
- Mild overgrowth, Long face, high forehead, prominent ears
- Pubertal Macroorchidism (80-90 %)
- Joint hyperlaxity and rare pectus
- Strabismus and Hyperopia
- Mitral valve prolapse
Developmental Issues
- Intellectual defeciency
- Autism Spectrum-like Hypersensitivity
- Language Delay and Cluttered Speech
- Hyperactivity which improves with age
Sotos Syndrome
Fragile X differential
Physical Issues
Developmental Issues
Prader-Willi Syndrome
- Paternal 15q11.2-q13 microdeletion (75 %)*
- Maternal disomy of chromosone 15 (20 %)*
- Imprinting defect (< 5 %)*
Physical Issues
- Prenatal low tone and activity
- Infantile low tone and poor feeding
- Short Stature (responds to Growth Hormone Tx)
- Central Obesity from Hyperphagia later on
- Scoliosis
- OSA (central and obstructive)
- Atypical saliva and enamel hypoplasia
- Glasses (strabismus, hyperopia, myopia)
Developmental Issues
- Motor delays (tone and coordination issues)
- Language delays (coordination)
- Mild intellectual delay
- Stubborn tantrums and manipulation
- Risk for psychosis
- High pain tolerance
