Genetic Flashcards
- What are the key features of Edwards syndrome (Trisomy 18)?
Trisomy 18: IUGR, clenched fists, rocker-bottom feet, micrognathia, VSD, poor prognosis
- Karyotype: 47,XX/XY+18
- What are the features of Klinefelter syndrome (47,XXY)?
Features: Tall stature, small testes, gynecomastia, learning difficulties, infertility
- Karyotype: 47,XXY
- How is Turner syndrome diagnosed?
Diagnosis: Karyotyping
- May be suspected with short stature and delayed puberty in girls
- What are the medical complications of Turner syndrome?
Complications: Coarctation of aorta, bicuspid aortic valve, renal anomalies, infertility, hypothyroidism, osteoporosis
- What are the key clinical features of Down syndrome (Trisomy 21)?
Features: Hypotonia, flat face, epicanthic folds, upslanting palpebral fissures, single palmar crease, sandal gap toe, intellectual disability
- What are the genetic and clinical features of Turner syndrome?
Turner: 45,X (or mosaicism), short stature, webbed neck, shield chest, lymphedema, primary amenorrhea
- What are the key features of Patau syndrome (Trisomy 13)?
Trisomy 13: Cleft lip/palate, holoprosencephaly, polydactyly, microphthalmia, severe ID
- Karyotype: 47,XX/XY+13
- What are the common medical complications associated with Down syndrome?
Complications: Congenital heart defects (AVSD), hypothyroidism, leukemia risk, hearing loss, GI anomalies (duodenal atresia), atlantoaxial instability
- What is the genetic cause and presentation of Fanconi anemia?
Fanconi anemia: AR/X-linked (DNA repair defects)
- Pancytopenia, short stature, radial anomalies, café-au-lait spots, leukemia risk
- What are the features of Bloom syndrome?
Bloom syndrome: AR, BLM gene (DNA helicase defect)
- Growth retardation, sun-sensitive rash, immunodeficiency, cancer predisposition
- What are the features and genetic defect in Ataxia-telangiectasia?
Ataxia-telangiectasia: AR (ATM gene)
- Cerebellar ataxia, oculocutaneous telangiectasia, recurrent infections, cancer risk
- What is the genetic basis and presentation of Beckwith-Wiedemann syndrome?
Beckwith-Wiedemann: Imprinting disorder (11p15, IGF2/H19)
- Macrosomia, macroglossia, organomegaly, omphalocele, Wilms tumor risk
- What are the types and clinical signs of osteogenesis imperfecta?
OI: COL1A1/2 gene mutation
- Features: Blue sclerae, fractures, hearing loss, dental issues
- Types I–IV, type II lethal
- What are the red flag signs that suggest a genetic syndrome in a pediatric patient?
Red flags: Multiple congenital anomalies, dysmorphic features, developmental delay, growth failure, consanguinity, family history
- What is the genetic basis and presentation of congenital adrenal hyperplasia (CAH)?
CAH: AR (most common 21-hydroxylase deficiency, CYP21A2 gene)
- Salt-wasting crisis, virilization, ambiguous genitalia in females
- What are the types of CAH and how are they diagnosed genetically?
Types: Classic salt-wasting, simple virilizing, non-classic
- Diagnosed by elevated 17-OH progesterone and genetic testing
- What are the features and diagnosis of Silver-Russell syndrome?
Silver-Russell: Hypomethylation of 11p15 or maternal UPD7
- Features: IUGR, triangular face, limb asymmetry, feeding difficulty
- What are the genetic and clinical features of Fragile X syndrome?
Fragile X: X-linked, CGG repeat on FMR1 gene
- Features: Macroorchidism, long face, large ears, autism, ID, hand-flapping
- What are the features and genetics of Alagille syndrome?
Alagille: AD (JAG1/NOTCH2 gene)
- Features: Cholestasis, butterfly vertebrae, posterior embryotoxon, cardiac defects, facial features
- What are the inheritance patterns and features of mitochondrial disorders?
Mitochondrial disorders: Maternal inheritance
- Affect high-energy tissues (muscle, brain), variable penetrance and severity
- What is genetic counseling and what are its main principles?
Genetic counseling: Process of advising patients on inherited conditions, recurrence risks, testing options, family planning
- What is the presentation and inheritance pattern of Marfan syndrome?
Marfan: AD (FBN1 gene mutation)
- Features: Tall, long limbs, lens dislocation, aortic dilation, scoliosis
- What are the common modes of inheritance in pediatric genetic disorders?
Modes: Autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant, mitochondrial, multifactorial
- What is the difference between genetic mosaicism and chimerism?
Mosaicism: Two cell lines from one zygote (postzygotic mutation)
- Chimerism: Two genetically distinct zygotes (e.g., twin fusion)
- What are the clinical features and inheritance of Rett syndrome?
Rett: X-linked dominant (MECP2 mutation), girls only
- Regression after 6–18 months, hand-wringing, seizures, autism features
- What is multifactorial inheritance and what conditions follow this pattern?
Multifactorial: Caused by gene-environment interactions
- Examples: Cleft lip/palate, neural tube defects, congenital heart defects, diabetes
- What are common X-linked disorders in pediatric practice?
Examples: Duchenne muscular dystrophy, Hemophilia A/B, G6PD deficiency, OTC deficiency, Fragile X syndrome
- What are examples of autosomal recessive disorders in pediatrics?
Examples: Cystic fibrosis, Phenylketonuria, Sickle cell anemia, Tay-Sachs, Congenital adrenal hyperplasia
- What are examples of common autosomal dominant genetic disorders in children?
Examples: Marfan syndrome, Neurofibromatosis type 1, Achondroplasia, Tuberous sclerosis, Noonan syndrome
- What are the key features of X-linked inheritance?
X-linked: Recessive disorders more common in males; females usually carriers
- No male-to-male transmission
- What are the key features of autosomal recessive inheritance?
Autosomal recessive: Both alleles must be mutated
- Often seen in consanguinity; parents are carriers; 25% risk with each pregnancy
- What are the key features of autosomal dominant inheritance?
Autosomal dominant: One copy of mutant gene causes disease
- Often multigenerational, variable expressivity, incomplete penetrance possible
- What are the features of Noonan syndrome and its inheritance?
Noonan: AD disorder (PTPN11 gene), short stature, webbed neck, CHD (pulmonary stenosis), low-set ears, cryptorchidism
- What is the difference between screening and diagnostic genetic tests in prenatal care?
Screening: Non-invasive (NIPT, serum markers, ultrasound)
- Diagnostic: Invasive (CVS, amniocentesis) with definitive chromosomal/genetic analysis
- What are the common genetic testing techniques used in pediatrics?
Testing: Karyotyping (chromosomal), FISH (microdeletion), CGH (CNV), WES/WGS (single gene or exome-wide), PCR for known mutations
- What are copy number variations and their clinical relevance?
CNVs: Gain/loss of DNA segments; detected by CGH
- Cause intellectual disability, autism, congenital anomalies
- How is Down syndrome diagnosed prenatally and postnatally?
Prenatal: Nuchal translucency + PAPP-A, quad screen, non-invasive prenatal testing (NIPT), amniocentesis
- Postnatal: Clinical features + karyotype (47,XY+21)
- What are the common chromosomal microdeletion syndromes in pediatrics?
Microdeletion syndromes: DiGeorge (22q11), Williams (7q11), Prader-Willi/Angelman (15q), Cri-du-chat (5p)
- What are the features of Angelman syndrome?
Features: Severe intellectual disability, happy demeanor, microcephaly, seizures, ataxia
- Chromosome 15q11–q13 (maternal deletion)
- What is uniparental disomy and how is it involved in Prader-Willi and Angelman syndromes?
Uniparental disomy: Both copies of a chromosome from one parent
- Paternal loss = Prader-Willi, Maternal loss = Angelman
- What are the features of Prader-Willi syndrome?
Features: Hypotonia, obesity, hypogonadism, almond-shaped eyes, short stature, developmental delay
- Chromosome 15q11–q13 (paternal deletion)
- What are the clinical features of Cri-du-chat syndrome?
Cri-du-chat: 5p deletion
- High-pitched cat-like cry, microcephaly, hypertelorism, ID, hypotonia
- What is the genetic basis and presentation of Williams syndrome?
Williams: Microdeletion on 7q11.23 (elastin gene)
- Elfin facies, supravalvular aortic stenosis, hypercalcemia, social personality
- What are the clinical findings in children with Cornelia de Lange syndrome?
Cornelia de Lange: Cohesin gene mutations (NIPBL)
- Synophrys, limb defects, micrognathia, growth delay, ID, behavior issues
- What are the genetic causes and features of Pierre Robin sequence?
Pierre Robin: Micrognathia → glossoptosis → airway obstruction
- Often part of Stickler syndrome (COL2A1 mutation)
- What is the presentation of 22q11.2 deletion syndrome (DiGeorge syndrome)?
22q11 deletion: CATCH-22 (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia)
- What are the key features and genetics of Gaucher disease?
Gaucher: AR (GBA gene)
- Types I–III, hepatosplenomegaly, anemia, bone pain, Erlenmeyer flask deformity
- Treat with enzyme replacement
- What is Zellweger syndrome and how does it present?
Zellweger: Peroxisomal biogenesis disorder
- Features: Hypotonia, large anterior fontanelle, craniofacial dysmorphism, seizures, liver dysfunction
- What are lysosomal storage diseases and their general features in children?
Lysosomal storage diseases: Inherited enzyme deficiencies causing accumulation of substrates
- Features: Neuroregression, organomegaly, skeletal abnormalities, coarse facies
- What is the clinical presentation of Tay-Sachs disease?
Tay-Sachs: AR (HEXA gene), Ashkenazi Jews
- Features: Neurodegeneration, hypotonia, exaggerated startle, cherry-red spot, no hepatosplenomegaly
- How does Niemann-Pick disease present in pediatrics?
Niemann-Pick: AR, sphingomyelinase deficiency (types A/B) or cholesterol trafficking (type C)
- Cherry-red spot, hepatosplenomegaly, hypotonia
- What is the clinical presentation of Kearns-Sayre syndrome?
Kearns-Sayre: Mitochondrial deletion
- Triad: Pigmentary retinopathy, external ophthalmoplegia, heart block (onset <20 yrs)
- What is Leigh syndrome and how does it present in children?
Leigh syndrome: AR or mitochondrial
- Neurodegeneration, hypotonia, lactic acidosis, symmetric basal ganglia lesions on MRI
- What are the features of MELAS syndrome in pediatrics?
MELAS: Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes
- Also has hearing loss, short stature, diabetes
- What are the key diagnostic criteria for Marfan syndrome?
Marfan criteria: Systemic score + aortic root dilation + ectopia lentis + FBN1 mutation
- Ghent nosology used
- What are the genetic and clinical features of achondroplasia?
Achondroplasia: FGFR3 gene (AD), 80% de novo
- Features: Short limbs, trident hands, macrocephaly, normal intelligence
- What are the genetics and clinical presentation of neurofibromatosis type 1?
NF1: AD (chromosome 17)
- Café-au-lait spots, neurofibromas, axillary freckling, Lisch nodules, optic glioma
- How is neurofibromatosis type 2 different from type 1?
NF2: AD (chromosome 22, merlin gene)
- Bilateral vestibular schwannomas, hearing loss, fewer skin signs
- What are the features and genetic cause of Smith-Lemli-Opitz syndrome?
Smith-Lemli-Opitz: AR, cholesterol synthesis defect (DHCR7 gene)
- Features: Microcephaly, cleft palate, syndactyly, genital anomalies, ID
- What are the features of tuberous sclerosis complex and its genetic basis?
Tuberous sclerosis: AD (TSC1/TSC2)
- Features: Ash-leaf spots, seizures, ID, facial angiofibromas, cardiac rhabdomyoma
