Syndromes/Genetics Flashcards
Gorlin’s syndrome
Aka Nevoid Basal Cell Syndrome
BCC, odontogenic keratocysts, falx calcifications
Genovese syndrome
bystander effect
CHARGE association
C-coloboma H-heart defect A-atresia of choana R-retarded growth G-genital abnormalities E-ear deformities
Short, wide, ear with little or no lobe, prominent antihelix, triangular concha, decreased cartilage, asymmetric (>50%)
Choanal atresia in 50-60%
Mutation in 8q11
CN anomalies: hyposmia/anosmia in 90-100%, swallowing difficulties in 70-90%, facial nerve paralysis in 40%
MEN 1
pancreas, parathyroid, pituitary
MEN 2
medullary carcinoma, parathyroid, pheochromocytoma
MEN 3
medullary carcinoma, pheochromocytoma, mucosal neuromas
What is a sequence?
a pattern of multiple anomalies derived from a single prior anomaly or mechanical factor.
Whast is a syndrome?
a set of symptoms occurring together; the sum of signs of any morbid state; a symptom complex.
What is an association?
the occurrence together of two or more phenotypic characteristics more often than would be expected by chance.
Pierre Robin sequence
micrognathia, glossoptosis, and cleft palate (50%)
there is posterior and superior positioning of the tongue
U-shaped cleft palate involving soft palate and posterior hard palate
Error in 1st branchial arch structures
GILLS
Pierre Robin Sequence management:
May help identify infants who will fail surgical management
GERD
Intubation preoperatively
Late operation (>2 weeks)
Low birth weight
Syndromic diagnosis
Stickler Syndrome
Collagenopathy, types II and XI
Typically AD, phenotype varies
PRS with or without CP, ocular abnormalities including retinal detachment, cataracts, high myopia, and glaucoma
Van der Woude syndrome
autosomal dominant syndrome characterized by a cleft lip or cleft palate, distinctive pits of the lower lips, or both
most common syndrome associated with cleft lip or cleft palate.
Velocardiofacial syndrome (VCFS)
DiGeorge - CATCH22 (22q11.2)
Cardiac Abnormality (especially tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate (overt or submucosal cleft)
Hypocalcemia/Hypoparathyroidism.
Treacher-Collins syndrome
Defect of 1st and 2nd arch development; TCOF1 gene locus implicated in inherited forms
40% have an affected parent
Midface hypoplasia, micrognathia, lower lid coloboma, microtia, CDHL, vision defets, downward sloping palpebral fissures
Oculauriculovertebral (OAV) syndrome
also known as Goldenhar’s syndrome, hemifacial microsomia, craniofacial microsomia, and 1st and 2nd branchial arch syndrome
Usually unilateral, right sided
Both AD and AR types described
triad of craniofacial microsomia, ocular dermoid cysts, vertebral anomalies
Mutation in Marfans syndrome?
- dominant trait
- carried by the gene FBN1, which encodes the connective protein fibrillin-1
Mutation in Cystic Fibrosis?
- autosomal recessive
- CFTR gene
- error of q31.2 locus of chromosome 7
What is Pendred Syndrome?
A genetic disorder leading to congenital bilateral SNHL and goiter and occasional hypothyroidism
Autosomal recessive inheritence
Mutations in the PDS gene, which codes pendrin protein (chromosome 7q31)
Same gene mutation also causes enlarged vestibular aqueducy syndrome (EVAS)
Effects iodide/chloride transport in thyroid, cochlea, kidneys
No specific treatment, just hormone replacement and hearing aids
What is Jervell and Lange-Nielsen syndrome?
- Type of long QT syndrome, causes the cardiac muscle to take longer than usual to recharge between beats.
- The disorder also contributes to hearing loss.
- Autosomal recessive
- Affects an estimated 1.6 to 6 in 1 million children
- Responsible for less than 10 percent of all cases of long QT syndrome.
- Mutations in the KCNE1 and KCNQ1 genes
- Proteins produced by these two genes work together to form a potassium channel that transports positively charged potassium ions out of cells.
- The movement of potassium ions through these channels is critical for maintaining the normal functions of the inner ear and cardiac muscle.
Treatment
- Beta-blocker like propranolol if the patients is asymptomatic or there is no documented syncope. Beta-blocker + dual mode/dual chamber/dual sensing pacemaker if the patient is symptomatic or there is documented syncope.
What is osteogenesis imperfecta?
aka brittle bone disease, or “Lobstein syndrome”
- born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen
- autosomal dominant
- mutations in the COL1A1 and COL1A2 gene
- Type I: the mildest and most common type—usually inherited
- Type II: the most severe type—frequently life-threatening and die young
- Type III: severe type—usually no family history
- Type IV: moderate type—often traced through family lines
What is Langer-Giedion Syndrome?
- aka Trichorhinophalangeal syndrome type II (TRPS2) or LGCR (Langer-Giedion Chromosome Region)
- Autosomal dominant
- Mild to Moderate learning difficulties
- Short stature
- Unique facial features
- Small head and skeletal abnormalities including bony growths projecting from the surfaces of bones
- Fine scalp hair, ears that may be large or prominent, broad eyebrows, deep-set eyes, a bulbous nose, long narrow upper lip, and missing teeth.
What is Melkersson-Rosenthal Syndrome?
Pathophysiology
unknown etiology
Symptoms
chronic or recurrent edema of the face (defining feature), recurrent unilateral or bilateral facial motor dysfunction, fissured tongue, cheilitis granulomatosa
- facial swelling and facial paralysis begin in childhood and early adolescence
Diagnosis
clinical history and exam, lip biopsy reveals dilated lymphatics and granulomatous changes with giant cells, may have elevated ACE levels during attacks
Treatment
empiric management with corticosteroids, may consider surgical decompression (controversial)
What is Eagles Syndrome?
Pathophysiology
elongated styloid process or ossified stylohyoid
ligament causes mechanical irritation of surrounding nerves
Symptoms
odynophagia, unilateral tonsilar pain, pain behind mandibular angle, referred otalgia, palpation at site reproduces pain
Diagnosis
radiography
Treatment
excision from intraoral or external approach
