Epigenetics, Imprinting, Chromosome Instability Syndromes Flashcards
upd(6)pat
- transient neonatal diabetes–> insulin-requiring hyperglycemia within 1st month of life
- low birth weight
- severe IUGR
- most cases involve chr 6 isodisomy
IMPRINTED GENES:
- IGF2R (insulin-like growth factor 2 receptor)
- PLAGL1/ZAC
upd(7)mat
- first documented UPD in humans
- significant pre and postnatal growth retardation
- 7-10% of patients with SILVER-RUSSEL SYNDROME
- heterogeneous phenotype
- body asymmetry
- triangular face
- prominent forehead
IMPRINTED GENES:
- GRB10 (growth suppressor)
- MEST/PEG1 - mesoderm
upd(11)pat
only a few cases reported for entire chromosome (lethal?)
mosaic segmental UPD observed in 10-20% of BW patients
IMPRINTED GENES:
- IGF2
- H19
Beckwith-Wiedemann Syndrome
- incidence
- phenotype
INCIDENCE: 1:13,000
PHENOTYPE:
- macrosomia; hemihyperplasia
- macroglossia
- visceromegaly
- childhood embryonal tumors (Wilms tumor, hepatoblastoma, neuroblastoma, etc)
- omphalocoele, umbilical hernia
- neonatal hypoglycemia
- renal abnormalities
upd(14)mat
mild to moderate motor/developmental delay
- hypotonia
- short stature
- precocious puberty
- other variable features
upd(14)pat
- polyhydramnios, low birth weight
- characteristic facial anomalies
- severe neurologic involvement!
- skeletal anomalies
ovarian teratoma
2 maternal genomes
embryonal tumor with ectodermal, mesodermal, endodermal germ layers
complete hydatidiform mole
2 paternal genomes
no embryo
large, abnormal, cystin placenta
most frequently results from fertilization of an oocyte without active nucleis followed by chromosome duplication
digynic triploidy
2 maternal and 1 paternal genomes
results in severe IUGR/small, underdeveloped placenta
early spontaneous abortion
“relatively good” embryo development
partial hydatidiform mole
results from diandric triploidy - 2 paternal genomes, 1 maternal
- large cystic placenta with molar changes
- fetus only if mosaic for normal cell line
MOST COMMON TRIPLOIDY - results from dispermy
Fanconi anemia
- characterized by
- clinical description
CHARACTERIZED BY
- congenital anomalies
- predisposition to bone marrow failure and malignancy
VARIABLE PHENOTYPE - 75% have physical features - 50% have radial-ray anomalies (ie bilateral absent thumbs and radii, unilateral hypoplastic thumb or bifid thumb) - short stature - hypogonadism predisposition to cancer, especially AML
Fanconi anemia diagnosis
- prevalence
- carrier frequency
- differentials
PREVALENCE: 1:100,000
carrier frequency about 1:300, but subpopulations vary
13 distinct complementation groups, with 60-80% falling in group C
DIFFERENTIAL: Holt-Oram syndrome, VACTERL association, TAR
very difficult to diagnose
Ataxia Telangiectasia
- characterized by:
- clinical description
CHARACTERIZED BY:
- progressive cerebellar ataxia, ocular and facial telangiectasias (widened blood vessels), immunodeficiency, frequent infections
- elevated AFP
- increased risk of cancer
- sensitivity to ionizing radiation
CLINICAL DESCRIPTION
- progressive gait and truncal ataxia
- progressive slurred speech
- 25% have myoclonic jerking, intention tremors
- most confined to wheelchair by 10 yo
- typically normal intelligence
Ataxia Telangiectasia
- prevalence
- gene/mutations
- differential diagnosis
PREVALENCE: 1: 89,000
GENE: ATM (11q22.3) - signal transduction network signaling
- cell cycle checkpoints
- recombination
- apoptosis
- other DNA damage cellular response
> 500 known mutations, no hotspots
- majority are nonsense/protein truncating
- sequencing is available, but laborious
DIFFERENTIAL: cerebral palsy, Friedrich’s ataxia, other chromosomal instability disorders
Bloom Syndrome
- Characterizations
CHARACTERIZED BY:
- pre- and postnatal growth retardation
- sun sensitivity
- erythematous facial sun lesions
- immunodeficiency
- diabetes
- infertility
- increased predisposition to cancer
