Genetics Flashcards
Leukemia associated with DS
Acute lymphocytic leukemia (but acute myeloblastic leukemia if in first 3 years of life)
Natural Hx of DS
– Major cause for early mortality is congenital heart disease
– Muscle tone improves with age
– Rate of development slows with age
– Early onset of Alzheimer disease
______is the second most common pattern of human malformation.
Edwards syndrome
SSx of Edwards syndrome
– Mental retardation
– Low-set, malformed ears; microcephaly, micrognathia; prominent occiput
– Clenched hand—index over third; fifth over fourth
Cardiac abn associated with Edwards
– VSD, ASD, PDA, cyanotic lesions,
Ortho abn associated with Edwards
– Rocker-bottom feet, hammer toe
GI abn associated with Edwards
– Omphalocele
Natural Hx of Edwards
– Many spontaneous abortions
– Feeble from birth
– Most do not survive first year
defect of midface, eye, and forebrain development → single defect in first 3 weeks’ development of prechordal mesoderm. It involves older maternal age
Patau syndrome
Asscn with Patau
– Scalp defects in parietal-occipital area (cutis aplasia)
– Postaxial polydactyly
Deletion asstd with WAGR syndrome
11p13; Wilms + Aniridia + GU anomalies + MR
– Decreased IQ (average IQ 85−90)
– Behavioral/psychiatric problems
– Long limbs (decreased upper:lower segment ratio)
Klinefelter Syndrome (XXY)
– Congenital lymphedema, residual puffiness over dorsum of fingers and toes
– Broad chest, wide-spaced nipples
– Low posterior hairline; webbed posterior neck
– Cubitus valgus (elbow) and other joint problems
– Horseshoe kidney, and other renal defects
Turner Syndrome (XO)
MC cardiac abn asstd with Turner
° Bicuspid aortic valve (number 1 cardiac anomaly)
° Coarctation
Natural Hx of Turner
– Decreased height velocity with delayed bone age
– Estrogen treatment indicated
– May increase height by 3−4 cm with growth hormone (GH)
Fragile X syndrome
Fragile site on _________in affected males and some carrier females—
Molecular diagnosis—variable number of repeat ______(preferred diagnosis = DNA-based molecular analysis)
long arm of X
CGG
Features of Fragile X
– Mild to profound mental retardation; learning problems
– Large ears, dysmorphic facial features, large jaw, long face
– Large testes—mostly in puberty (macroorchidism)(fertile
Genetic abn in Beckwith-Wiedemann Syndrome
– IGF-2 disrupted at 11p15.5 (imprinted segment)
Findings of Beckwith-Wiedemann Syndrome
– Macrosomia
– Macroglossia—may need partial glossectomy
– Pancreatic beta cell hyperplasia—excess islets → hypoglycemia
What dxtic test to do in pts with Beckwith-Wiedemann Syndrome
obtain ultrasounds and serum AFP every 6 months through 6 years of age to look for Wilms tumor and hepatoblastoma
– Most with deletion at 15q11-q13–imprinted segment
– Paternal chromosome responsible
Prader-Willi Syndrome
Prader-Willi Syndrome features
– Obesity—onset from 6 months to 6 years
– Mild to severe mental retardation
– Food-related behavioral problems (binge eating)
– Small hands and feet, puffy; small genitalia
– Hypothalamic—pituitary dysfunction (growth, thyroid, adrenal)
– Severe MR
– Paroxysms of inappropriate laughter
– Absent speech or <6 words (100%); most can communicate with sign language
Angelman Syndrome (Happy Puppet Syndrome)
Why is Angelman Syndrome called Happy Puppet Syndrome)
Ataxia and jerky arm movements resembling a puppet’s movements (100%)
Mandibular hypoplasia in utero → posteriorly placed tongue → posterior palatal, shelves → cleft palate and other palatal abnormalities
Robin Sequence (Pierre Robin
Isolated finding or associated with some syndromes of Robin Sequence (Pierre Robin)
fetal alcohol syndrome, Edwards Syndrome
Findings in Robin Sequence (Pierre Robin
– Micrognathia
– Retroglossia → possible airway obstruction
– Cleft soft palate and other abnormalities
Mutations in gene for fibroblast growth factor receptor 3 at 4p16.3 (FGFR3)
Achondroplasia/Hypochondroplasia
FIndings in Achondroplasia/Hypochondroplasia
– Short stature (increased upper-to-lower segment ratio; short-limbed dwarfism)
– Proximal femur shortening
– Megalocephaly, small foramen magnum (may have hydrocephalus), small cranial
base, prominent forehead
– Lumbar lordosis
Cx of Achondroplasia/Hypochondroplasia
Early cervical compression, respiratory problems, obstructive and central apnea, later cardiovascular disease
– Autosomal dominant with wide variability
– Mutation in fibrillin gene (FBN1)—15q21.1
Marfan Syndrome
Bony abn asstd with Marfan
– Arm span > height – Arachnodactyly – Decreased U:L segment ratio (as with XXY) – Joint laxity with kyphoscoliosis – Pectus excavatum or carinatum
Ophtha abn asstd with MArfan
Lens subluxation (upward; defect in suspensory ligament); secondary glaucoma, myopia, retinal detachment
Cardiac abn asstd with MArfan
Ascending aortic dilatation with or without dissecting aneurysm (uncommon in children and adolescents unless case is severe) with secondary aortic regurgitation.
Mitral valve disease (MVP and regurgitation) is the most common in children.
NAtural course of Marfan
– Prevent scoliosis
– Vascular complications chief cause of death
– Evaluate heart and aorta
– Droopy ears
– Hyperextensible skin, fragile, easy bruisability, poor wound healing
– Joint hyperlaxity; tendency toward hip, shoulder, knee, and clavicular dislocation
Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome cardiac association
– MVP, tricuspid valve prolapse, aortic root dilatation; dissecting aneurysm, ASD
Ophtha findings of Ehlers-Danlos Syndrome
Blue sclera, myopia, glaucoma, ectopia lentis, retinal detachment
Cardiac anomalies in EDS:
VSD > ASD, tetralogy of Fallot
• Similar features with prenatal exposure to carbamazepine, valproate, primidone,
and phenobarbital
• No dose-response relationship has been demonstrated
• Growth deficiency
Fetal Hydantoin Syndrome
Physical features of Fetal Hydantoin Syndrome
Hirsutism
• Cupid’s-bow lips
- Midface hypoplasia; cleft lip
- Cardiac defects
- Long, thin fingers and toes; convex nails
- Meningomyelocele
Fetal Valproate Syndrome
- Mild facial asymmetry; bilateral microtia/anotia (ear); facial nerve paralysis ipsilateral to ear; narrow, sloping forehead; abnormal mottling of teeth
- Conotruncal malformations
- CNS malformations
Retinoic Acid Embryopathy (from Isotretinoin)
Upto when is taking (from Isotretinoin) safe?
No problems if stopped before 15th postmenstrual day
– Renal agenesis/dysgenesis or other type of urinary tract defect must occur prior to 31 days’ gestation → oligohydramnios (also from chronic leakage)
– Leads to fetal compression (mid-face, ears)
– Lack of alveolar sac development → pulmonary hypoplasia
Potter Sequence
What is the Potter facies
hypertelorism, epicanthal folds, low-set flattened ears, micrognathia, compressed flat nose
VACTERL Association
V = Vertebral defects A = Anal atresia (imperforate anus) C = Cardiac defects (VSD and others) T = TE fistula E = Esophageal atresia R = Renal defects L = Limb defects (radial
CHARGE Association
C = Coloboma (from isolated iris to anophthalmos; retinal most common) H = Heart defects (TOF, PDA, and others) A = Atresia choanae R = Retardation of growth and/or development G = Genital hypoplasia (in males) E = Ear anomalies and/or deafness
