Upgrade to remove ads
100 syndromes - DiGeorge, Alagille
Terms in this set (37)
what is the typical deletion size in DiGeorge syndrome?
list potential genes of interest in DiGeorge syndrome
TBX 1, COMT, GPT 1 PT, UFDIL
List gastrointestinal abnormalities in DiGeorge syndrome. Why?
Severe dysphagia, constipation, structural abnormalities. Due to dysmotility of the GI tract attributed to TBX1?
What autoimmune diseases are common in DiGeorge syndrome?
JRA, autoimmune thyroiditis and IgA deficiency
Name some additional disorders on the DiGeorge phenotypic spectrum:
VCF, Conotruncal anomaly face syndrome, Opitz G/BBB synrome, Sedlackova syndrome, Cayler cardiofacial syndrome.
Typical clinical features of DiGeorge syndrome include:
congenital heart disease, immune dysfunction, palate abnormalities, feeding problems, developmental delay and disability ,hypocalcemia, renal anomalies, psychiatric disorders, And medial deviation of the internal carotids
patients with the DiGeorge syndrome phenotype without the typical deletion have what other deletion?
10 P13-P14 deletion
other than FISH, what molecular test can be used to diagnose DiGeorge syndrome?
ML PA (Multiplex ligation PCR amplification)
Describe some features of the 22 q. 11. 2 micro-duplication syndrome.
Features include learning difficulties autistic disorder growth retardation hypotonia and cardiac anomalies
Features include prematurity growth delay developmental delay intellectual disability skeletal abnormalities cardiac malformations (truncus arteriosus)
Genes responsible are thought to be CRKL and ERK2/map K1, UEB213.
Alagille syndrome: Responsible genes
JAG1, notch 2 (JAG1 encode the ligand for the NOTCH transmembrance receptor)
Alagille syndrome Diagnostic criteria:
Bile duct paucity on liver biopsy +3 of the following: Cardiac defects (pulmonary artery, tetralogy of Fallot), eye defects (posterior embryotoxon), facial features (triangular facies, deep set eyes, broad forehead, prominent pointed chin, low set ears), skeletal defects, developmental delay, growth failure.
If there is an affected individual, one clinical feature is needed for diagnosis (variable expressivity)
The pathogenic mechanism for Alagille syndrome is:
haploinsufficiency. A truncated protein product is produced which prevented from binding efficiently to the cell membrane. (Jag1)
Mechanism other than single gene defects leading to Alagille syndrome:
microdeletion of 20p12, in approximately 7% of affected individuals.
specific pathogenic mutations in NOTCH2 lead to what other disorder? What are the features? What is this type of change referred to as?
Hajdu-Cheney syndrome: focal bone destruction, osteoporosis, craniofacial dysmorphology, renal cysts, cleft palate, and cardiac defects. Mutations in the last exon (exon 34) disrupt the intracellular PEST (proline-glutamate-serine-threonine-rich) domain and decrease clearance of the notch intracellular domain, thus increasing Notch signaling.
Somatic pathogenic NOTCH2 mutations lead to:
Splenic marginal zone lymphoma
Typically adrenergic stimuli, including exercise and sudden emotion (Fear/excitement triggers!).
Exercise and at rest and with auditory stimuli, such as alarm clocks and phones (everything!)
Slower heart rates during rest periods and sleep (sleeping sickness... scary). SUNDS (sudden, unexpected nocturnal death syndrome - South Asians)
Jervell-Lange Nielsen disorder
AR form of Romano-Ward (AD prolonged QT, LQT1), also has deafness.
LQT genes (some of them...)
SCN5A is responsible for what % of Brugada syndrome?
15 to 30%
Brugada syndrome is diagnosed based on
characteristic EKG abnormalities (V1-V3 elevation in ST segment "Coved
little hump), family history of sudden death, personal hx of syncope.
Quinidine (normalizes the ST segment elevation)
BRAF, MEK one and MEK 2, and KRAS. Members of the map(mitogen activated protein) kinase pathway.
clinical features of CFC:
cardiac abnormalities, dermatologic abnormalities (sparse or curly hair, atopic dermatitis keratosis pilaris, ichthyosis), dysmorphic facial features (macrocephaly with broad forehead,spurs curly hair bitemporal narrowing, shallow orbits, lack of eyebrows and/or eyelashes, webbed neck, low set ears, hypertelorism, coarse facies), developmental delay, seizures, poor growth and feeding.
Costello syndrome Gene:
HRAS (map kinase pathway)
clinical features of Costello syndrome:
macrocephaly, coarse facies, intellectual disability, thickened lips, bulbous nose, thick earlobes, thin deep set nails, decreased range of motion, CHD, papillomas of the perioral, nasal, and anal regions
early lethal form of Costello syndrome:
G12VHRAS is associated with respiratory distress, hypertrophic cardiomyopathy, or malignant tachycardia, resulting in early death.
Neoplasms associated with Costello syndrome:
rhabdomyosarcoma and neuroblastoma (15%)
diagnostic features of hereditary hemorrhagic telangiectasia (HHT, Osler Weber Rendu)
recurrent epistaxis, mucocutaneous telangiectasias, visceral (pulmonary, cerebral, hepatic, spinal, gastrointestinal, pancreatic), AVM, first degree relative with the diagnosis of HHT.
genes associated with HHT:
ENG (noted to have a higher frequency of pulmonary AVM), ACVRL1/ALK1, SMAD4 (1-2% of cases, leads to juvenile polyposis syndrome and HHT).
in Holt-Oram syndromewhich carpal bone is always affected?
genes associated with Holt-Oram syndrome
pathophysiologic mechanism of Holt-Oram syndrome
the TBX5 mRNAs are rapidly degraded, or the DNA binding sites is affected preventing proper activity.
the no longer the technical name of the syndrome LEOPARD stands for
lentigines, EKG anomalies, ocular space hypertelorism, pulmonic stenosis, abnormalities of the genitalia, retardation of growth, and deafness.
Ataxia Telangectasia is associated with which translocation?
Sets found in the same folder
SMP 8 22q11.2 deletion syndrome (patient day)
22q11.2 Deletion Syndrome (DiGeorge Syndrome, Velo…
22q11.2 deletion syndrome (DiGeorge)
DiGeorge Syndrome (DGS or DGA)- BOD Exam 1
Sets with similar terms
Genetic terms mixed
Medical Conditions - Keywords
Other Quizlet sets
Ch. 5 health science
Ch. 7 - Nervous System
Quiz Questions for Neuroscience
Nutrition 1000 Exam 2