Untitled Deck Flashcards
(41 cards)
What genes/changes cause Alagille Syndrome
JAG1 seq (83%), JAG1 del (11%), NOTCH2 (2.5%)
What is the disease mechanism for Alagille?
JAG1 truncated protein product rendering it unable to bind to the cell membrane resulting in functional haploinsufficiency
What are the proteins and gene locations in Alagille?
JAG1 = jagged 1 on 20p12.2, NOTCH2 = neurogenic locus notch homolog protein 2 on 1p12
Clinical features of Alagille syndrome?
Bile duct paucity, cardiac defects (peripheral PS stenosis), cholestasis, skeletal abnormalities (butterfly vertebrae), eye (posterior embryotoxon), characteristic facial features, DD, growth failure
Inheritance pattern for Alagille
autosomal dominant, but 50-70% de novo
What are the facial features of Alagille
prominent/broad forehead, deep-set eyes w/ moderate hypertelorism, pointed chin, saddle or straight nose w/ bulbous tip
What is the primary gene, protein, and cytogenetic location for Brugada Syndrome
SCN5A, sodium channel protein type 5 subunit alpha, 3p22.2
What is the inheritance pattern for Brugada?
autosomal dominant. Except for KCNE5 which is XLR
What is the disease mechanism for Brugada?
LOF mutations in SCN5A cause lack of expression of or acceleration in the inactivation of cardiac sodium channels
What is a common clinical feature of Brugada Syndrome related to sleep?
Nocturnal agonal respiration
This refers to abnormal breathing patterns during sleep, often associated with serious medical conditions.
In which leads are ST-segment abnormalities observed in Brugada Syndrome?
Leads V1-V3 on EKG
These leads are part of a standard 12-lead electrocardiogram used to assess heart function.
What is a significant risk associated with Brugada Syndrome?
High risk of ventricular arrhythmias and sudden death
Ventricular arrhythmias can lead to life-threatening heart rhythms and sudden cardiac events.
At what stage of life does Brugada Syndrome primarily manifest?
Primarily in adulthood
Symptoms and complications typically arise in adult patients.
What is the mean age of sudden death in individuals with Brugada Syndrome?
40 years
This statistic highlights the serious nature of the condition and its impact on lifespan.
How may Brugada Syndrome present in infants?
As SIDS or sudden unexpected nocturnal death
SIDS stands for Sudden Infant Death Syndrome, which is a critical concern in pediatric populations.
What family history may be relevant in cases of Brugada Syndrome?
Family history of sudden cardiac death
This can indicate a genetic predisposition to arrhythmias and related conditions.
What is the management for Brugada syndrome?
implantable defibrillators (controversial in ASx patients)
What medication is used to treat electrical storm in Brugada patients?
isoproterenol
What circumstances should be avoided in Brugada syndrome?
fever, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic antagonists, TCAs, 1st gen antihistamines, cocaine, class 1C antiarrhythmic drugs, Class 1A agents (procainamide, disopyramide)
What are the genes/proteins and their locations that cause Cardio-Facio-Cutaneous (CFC) syndrome
BRAF1 (B-Raf proto-oncogene serine/threonine protein kinase) on 7q34, MAP2K1 on 15q22.31, MAP2K2 on 19q13.3 (mitogen-activated protein kinase 1 and 2), KRAS (GTPase Kras) on 12p12.2
What is the inheritance pattern for CFC Syndrome
Autosomal dominant, but majority are de novo
What is the disease mechanism for CFC syndrome
sustained activation of the Ras MAPK pathway downstream effectors: MEK and/or ERK
What cardiac abnormalities are seen in CFC syndrome?
pulmonic stenosis, septal defects, hypertrophic cardiomyopathy, arrhythmias
What neurologic manifestations are in CFC syndrome?
hypotonia, seizures, mild-severe ID
