1) Chromosomal Disorders:
Down Syndrome:
- Genetics: trisomy 21, Robertsonian translocation, mosaic
- Features:
- Eyes: upward slanting palpebral fissures, Brushfield spots (speckling of iris), prominent epicanthic folds
- Ears: small low-set ears, hearing loss
- Head: mental retardation, mild microcephaly, flat occiput, protruding tongue
- Neck: short neck, atlanto-axial instability, hypothyroidism
- Heart: AVSD > VSD > PDA, ASD, MVP
- GI: duodenal atresia, Hirshsprung
- MSK: small stature, hypotonia, single transverse palmar crease, brachydactyly, wide sandal gap
- Others: ALL, primary gonadal deficiency
Edward’s Syndrome:
- Genetics: trisomy 18 (non-disjunction)
- Features:
- General: SGA, growth deficiency
- Head: mental retardation, microcephaly, prominent occiput, micrognathia
- Heart: VSD (most commonly)
- MSK: short sternum, clenched hands + overriding fingers, rocker-bottom feet, hammer toe
- Others: omphalocele
Patau Syndrome:
- Genetics: trisomy 13
- Features:
- Eyes: holoprosencephaly, microphthalmia
- Head: severe mental retardation, microcephaly, cutis aplasia (scalp defects in parietal-occipital area), cleft lip\palate
- Kidney: fused kidneys
- MSK: post-axial polydactyly
- Others: SGA, single umbilical A
Klinefelter Syndrome:
- Genetics: 47, XXY (boys)
- Findings:
- Tall, slim, long limbs, feminine body build, gynecomastia
- Hypogonadism, hypogenitalism, infertility
- Decreased IQ, behavioral\psych problems
Turner Syndrome:
- Genetics: 45, XO (girls)
- Findings:
- Neck: webbed\broad neck, low posterior hairline, hypothyroidism
- Heart: bicuspid aortic valve, coarctation
- Kidney: horseshoe kidneys, unilateral renal agenesis
- Gonadal: hypoplastic “streak” ovaries, primary amenorrhea, infertility
- MSK: short stature, broad-chest, wide-spaced nipples, lymphedema and puffiness of hands\feet, cubitus valgus
2) Genetic Disorders:
Fragile X Syndrome:
- Genetics: CGG repeats, X-linked dominant (more in boys), MCC of inherited MR
- Findings:
- Mental retardation, behavioral and learning problems
- Long face, large ears, large jaw, large testes (macroorchidism, fertile)
Prader-Willi Syndrome:
- Genetics: deletion at 15q11-13 imprinted segment -> paternal
- Findings:
- Babies -> floppy(hypotonia), difficulty feeding, poor growth, FTT
- Children -> obesity (wt gain at 1-6 yrs), binge eating, hypothalamic-pituitary dysfunx
- Puffy, small hands\feet, small genitalia
Angelman Syndrome “Happy Puppet Syndrome”:
- Genetics: deletion at 15q11-13 imprinted segment -> maternal
- Findings:
- Severe mental retardation,
- Profound speech impairment, paroxysms of inappropriate laughter
- Ataxia, jerky arm movements, seizures
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Marfan Syndrome:
- Genetics: AD, mutation in the FBN1 gene on chr 15q
- Findings:
- General: tall, slim, long limbs, long fingers
- MSK: pectus malformation, kyphoscoliosis, joint laxity
- Eyes: myopia, lens dislocation
- Heart: floppy mitral valve, dilatation of the aortic root, dissecting aneurysm
Ehlers-Danlos Syndrome:
- Genetics: AD, many subtypes (MC is type 1)
- Findings:
- Eyes: blue sclera, myopia, ectopia lentis, glaucoma, retinal detachment
- Head: intracranial aneurysms, droopy ears
- Heart: aortic root dilatation, mitral\tricuspid valve prolapse, dissecting aneurysm
- Skin: hyper-extensible, fragile, easy bruising, poor wound healing
- Joints: hyper-laxity, dislocations
Achondroplasia\Hypochondroplasia:
- Genetics: AD, mutation in FBFR 3
- Findings:
- Short-stature (increased upper-to-lower segment ratio, short-limbed dwarfism)
- Megalocephaly, small foramen magnum, small cranial base, prominent forehead
- Lumbar lordosis
Di George Syndrome:
- Genetics: microdeletion on 22q11
- Findings:
- Subtle dysmorphism: down-slanting eyes, wide nasal bridge, small mouth, cleft lip\palate
- Thymus aplasia (T-cell def), parathyroid aplasia (hypocalcemia)
- Heart: aortic arch abnormalities, TOF
Noonan Syndrome:
- Genetics: AD, mutation in PTPN11 on 12q
- Findings:
- Inverted-triangle shaped head, hypertelorism, ptosis, webbed neck
- Chest malformation: pectus carinatum superiorly + pectus excavatum inferiorly
- CHD esp pulmonary stenosis
- Undescended testes
Williams Syndrome:
- Genetics: microdeletion on 7q11 (encompasses elastin gene)
- Findings:
- Peri-orbital fullness, star-like pattern of iris, anteverted nares, full cheeks, wide mouth, small widely spaced teeth
- CHD (supravalvular aortic stenosis)
3) Sequences:
Potter Sequence:Â
- Due to renal agenesis\dysgenesis -> oligohydramnios -> fetal compression
- Findings:
- Pulmonary hypoplasia -> respiratory insufficiency
- Face -> hypertelorism, compressed flat nose, low-set flattened ears
- Joint contractures, hands\feet deformities, limb anomalies
Peirre Robin Sequence:
- Can be and isolated finding or associated w\ other syndromes (FAS, Edward’s)
- Findings:
- Micrognathia + retroglossia -> risk of airway obstruction, cleft soft palate
- Micrognathia + retroglossia -> risk of airway obstruction, cleft soft palate
4) Associations:
WAGR Syndrome:
- Wilms
- Aniridia
- GU anomalies
- Retardation, mental
CHARGE Association: (mutation in chr 8)
- Colobomas of the eye
- Heart defects (TOF, PDA)
- Atresia choanae
- Retarded growth\development
- Genital hypoplasia (in males)
- Ear anomalies\deafness
VACTREL Association:
- Vertebral defects
- Anal atresia (imperforate anus)
- Cardiac defects
- TEF
- Esophageal atresia
- Renal defects
- Limb defects (radial)
Download the PDF version: here
References:
- Kaplan step 2 lecture notes
- Master the boards