Genetics and Syndromes

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 deficiencySyndromes 1


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: omphaloceleSyndromes 2


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 ASyndromes 3


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 valgusSyndromes 4


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)Syndromes 5


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 genitaliaSyndromes 6


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


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 aneurysmSyndromes 7


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, dislocationsSyndromes 8



  • 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 lordosisSyndromes 9


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, TOFSyndromes 10


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 testesSyndromes 11


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)Syndromes 12


3) Sequences:

Potter Sequence: 

  • 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 anomaliesSyndromes 13


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 palateSyndromes 14


4) Associations:

WAGR Syndrome:

  • Wilms
  • Aniridia
  • GU anomalies
  • Retardation, mentalSyndromes 15


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)



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