Genetic Disorders/Inborn Errors Of Metabolism Flashcards Preview

Pediatrics > Genetic Disorders/Inborn Errors Of Metabolism > Flashcards

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?

15; fibrillin

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)

FISH probes

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

FISH probe


Noonan syndrome – chromosome? Clinical features? Diagnosis?

Chromosome 12

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?


Cardiac anomaly
Abnormal feces
Thymic hypoplasia
Cleft palate
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



Vertebral defects
Anal atresia
Cardiac (VSD's)
Tracheoesophageal fistula
Renal defects
Limb defects (radial hypoplasia, polydactyly)


CHARGE association?

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
Autosomal dominant

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

FISH probes


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?

1. SGA
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?

Chromosome 5

Microcephaly, mental retardation, cat-like cry, hypertelorism (Increased distance between eyes)


Clinical features of down syndrome?

1. Craniofacial – Crutchfield spots (speckled irises)
2. Hypotonia
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
2. Leukemia
3. Celiac disease
4. Alzheimer's disease
5. OSA
6. Conductive hearing loss
7. Hypothyroid
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)
7. Hypothyroidism

Chromosome analysis


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

Chromosomal analysis


Klinefelter syndrome – clinical features? Diagnosis?

1. Tall stature
2. Hypogonadism with delayed puberty
3. Gynecomastia
4. Variable intelligence
5. Behavioral findings – antisocial behavior, excessive shyness, aggression

Chromosome analysis


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?

Severe oligohydramnios

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?

SGA, polycythemia

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


Abnormalities associated with maternal use of propylthiouracil? Warfarin?

Hypothyroidism, goiter

Hypoplastic nose with deep groove, hypoplastic nails, epiphyseal stippling