Flashcards in Genetic Disorders/Inborn Errors Of Metabolism Deck (36):
Malformation versus deformation versus disruption
Abnormal process forms abnormal tissue (bladder extrophy from failure of infraumbilical mesenchyme to migrate)
Mechanical forces under normal tissue resulting in abnormal tissue
Normal tissue becomes abnormal after being subjected to destructive forces
Causes of elevated AFP?
1. Neural tube defects
2. multiple gestation pregnancies
3. underestimated gestational age,
5. Ventral abdominal wall defects
6. Fetal demise
Low AFP levels associated with?
1. Overestimated gestational age
2. Trisomies 21 and 18
3. intrauterine growth retardation
Triple markers for down syndrome? Trisomy 18?
Low AFP, low unconjugated estriol, high beta-hCG
Low AFP, low unconjugated estriol, low beta-hCG
Ways to genetically evaluate fetus? (And best time to do so)?
1. Chorionic villus sampling (10 to 13 weeks)
2. Amniocentesis (16 to 18 weeks)
3. Percutaneous umbilical blood sampling
Marfan syndrome – chromosome? Gene? Clinical features? Rule out? Complications?
1. Skeletal findings (tall stature, long fingers, pectus excavator, scoliosis)
2. Ocular findings (upward lens subluxation, Retinal detachment)
3. Cardiovascular (aortic root dilatation, mitral valve prolapse, aortic regurgitation)
Rule out homocystinuria
Endocarditis, retinal detachment, aortic dissection
Prader-Willi syndrome – chromosome? Clinical features? Diagnosis? Complications?
Absence of parental chromosome 15
1. Almond shaped eyes, fishlike mouth
2. Failure to thrive followed by obesity
3. Short stature with small hands/feet
4. Neuro - Hypotonia, mental retardation, learning disabilities, behavioral problems
5. Hypogonadism (small penis/testes or cryptorchidism)
1. Infancy – poor sucking, feeding problems, developmental delay
2. In childhood – obesity and OSA
3. In adulthood – cardiac disease, type two diabetes
Angelman syndrome – chromosome? Clinical features? Diagnosis?
Deletion of maternal chromosome 15 segment
1. Neurologic – ataxia, jerking arm movements, inappropriate laughter, mental retardation ("happy puppet")
2. Craniofacial – small head, large mouth, tongue protrusion, blonde hair, blue eyes
Noonan syndrome – chromosome? Clinical features? Diagnosis?
1. Skeletal – short and shield chest
2. Craniofacial – Web neck, low hairline, widely spaced eyes, low-set ears, epicanthal skin folds
3. Cardiac – right sided heart lesions (pulmonary valve stenosis)
4. Mental retardation
Diagnosis based on clinical features
DiGeorge syndrome – defect? Clinical features? Diagnosis? Complications?
Structures from third and fourth pharyngeal pouch
1. Craniofacial – small chin, ear anomalies
2. Cardiac – aortic arch anomalies, VSDs, tetralogy of Fallot
3. Thymus/parathyroid hyperplasia – cell-mediated immunodeficiency, severe hypocalcemia
FISH probes on chromosome 22
Infections and seizures
Velocardiofacial syndrome - Clinical features? Diagnosis?
1. Craniofacial – cleft palate, wide nose, short chin, fish-shaped mouth
2. Cardiac – VSDs, right-sided aortic arch
3. Neurologic – hypotonia, learning disabilities
FISH probes for chromosome 22
New proposed name for DiGeorge syndrome and velocardiofacial syndrome?
Chromosome 22 defect
Elhers-Danlos syndrome – defect? Clinical features? Diagnosis? Complications?
Defective type IV collagen
1. Musculoskeletal – hyper extensible joints
2. Derm – velvety, loose, fragile skin. Poor wound healing and tissue paper scars
3. Cardio – MVP, aortic root dilatation easy bruising
4. G.I. – rectal prolapse, hernias
Diagnosis based on clinical findings
Complications – aortic dissection, G.I. bleeding
Osteogenesis imperfecta – defect? Clinical features? Diagnosis? Complications?
Abnormal type one collagen
1. Blue sclera
2. Frequent fractures, scoliosis, osteoporosis/osteopenia
3. Yellow or gray-blue teeth
4. Easy bruisability
Diagnosis based on decreased type I collagen synthesis in fibroblasts
Complications: early conductive hearing loss and skeletal deformities
Limb defects (radial hypoplasia, polydactyly)
1. Colobomas - (Absence or defect of ocular tissue), impaired vision
2. heart defects – tetralogy of Fallot
3. Atresia of nasal passages
4. Retardation of growth and cognition
5. Genital anomalies – genital hypoplasia
6. Ear defects – cup shaped and hearing loss
Williams syndrome – chromosome/Gene? Heredity? Clinical features? Diagnosis?
Chromosomes 7/elastin Gene
1. Elf face – flattened nasal bridge, round cheeks
2. Loquacious personality and mental retardation
3. Supravalvular aortic stenosis
4. Idiopathic hypercalcemia
5. Connective tissue defects – hoarse voice, hernias
Cornelia de Lange? Clinical features? Diagnosis?
1. SGA and FTT
2. Craniofacial – single eyebrow (synopheys), curly eyelashes, microcephaly, down-turned upper lip
3. infantile hypertonia
4. Mental retardation
5. Small hands/feet
6. Cardiac defects
7. Behavioral – autistic features, no facial expression, self-destructive tendencies
Russell-Silver syndrome – clinical features?
2. Craniofacial – small triangular face, prominent for head, head looks large but normal head circumference
3. Skeletal – short stature and lean asymmetry
4. Café au lait spots
5. Excessive sweating
Pierre Robin syndrome – clinical features? Complications?
1. Cleft lip/palate
2. Large tongue
Recurrent otitis media and upper airway obstruction
Cri du chat – Chromosome? Clinical features?
Microcephaly, mental retardation, cat-like cry, hypertelorism (Increased distance between eyes)
Clinical features of down syndrome?
1. Craniofacial – Crutchfield spots (speckled irises)
3. Mental retardation
4. Musculoskeletal – single Palmer creases, wide toe spacing
5. G.I. – duodenal atresia, Hirschsprung's disease, pyloric stenosis
6. Cardiac features – endocardial cushion defects
Complications of down syndrome?
1. Atlantoaxial spine instability
3. Celiac disease
4. Alzheimer's disease
6. Conductive hearing loss
8. Cataracts, glaucoma, refractive errors
Clinical findings of Trisomy 18? Prognosis?
1. Neuro – mental retardation and hypertonia with scissoring lower extremities
2. Small facial features
3. Musculoskeletal – clenched hands, overlapping digits, rocker bottom
95% die within the first year
Turner syndrome – clinical features? Diagnosis?
1. Short stature
2. Webbed neck
3. Shield chest with broadly spaced nipples
4. Sign of dorsum of hands and feet
5. Ovarian dysgenesis
6. Left-sided heart lesions (coarctation, bicuspid aortic valve, hypoplastic left heart)
Fragile X syndrome – clinical features? Diagnosis?
1. Mental retardation
2. Craniofacial – large ears, macrocephaly, blue irises
3. Large testes during puberty
4. Behavioral – emotional instability, autistic features, ADHD
Klinefelter syndrome – clinical features? Diagnosis?
1. Tall stature
2. Hypogonadism with delayed puberty
4. Variable intelligence
5. Behavioral findings – antisocial behavior, excessive shyness, aggression
Classifications of skeletal dysplasias?
1. Rhizomelia – Proximal long bone abnormalities (short humerus/femur)
2. Mesomelia - medial long bone abnormalities (short ulna/tibia)
3. Acromelia – distal abnormalities (small hands/feet)
4. Spondylodysplasias – Spinal abnormalities
Most common skeletal dysplasia? Type? Inheritance? Clinical features? Diagnosis? Complications?
Achondroplasia; rhizomelia gene; autosomal dominant; fibroblast growth factor receptor 3 gene
1. Craniofacial – megalocephaly, foreman magnum stenosis, midface hypoplasia
2. Skeletal findings – lumbar kyphosis in infancy which becomes lumbar lordosis, limb shortening, joint hyperextensibility, trident-shaped hands
3. Recurrent otitis media with conductive hearing loss
Clinical features and radiographs
1. Foreman magnum stenosis leading to hydrocephalus or cord compression (can cause sudden infant death)
2. Obstructive sleep apnea
3. Severe bowed legs and back pain
Potter syndrome? Caused by? Leads to?
1. Chronic amniotic fluid leak
2. Intrauterine renal failure caused by bilateral renal agenesis, polycystic kidneys, obstructive uropathy
1. Lung hypoplasia
2. Fetal compression – limb abnormalities and squashed facial features
Amniotic band syndrome? Caused by? Leads to?
Fluid leaks into intrauterine constraints causing amnion to wrap around fetus
Rupture of amniotic sac
Limb scarring and amputation
Most common teratogen? Features?
Microcephaly, SGA, short palpebral fishers, mental retardation, ADHD, VSD
Anomalies associated with maternal cigarette smoking? Cocaine?
Intrauterine growth retardation, microcephaly, GU abnormalities
Abnormalities associated with maternal use of diethylstilbestrol? Isotretinoin? Thalidomide?
Cervical carcinoma, GU abnormalities
CNS malformations, cardiac defects, thymic hyperplasia
Phocomelia (Flipper like appendages)
Abnormalities associated with maternal use of phenytoin? Valproic acid?
Wide anterior fontanelles, low hairline, small nails, cardiac defects
Narrow head, high forehead, midface hypoplasia, spina bifida, cardiac defects, convex nails