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 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

 

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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

 

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)

 

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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 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

 

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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)

 

 

 

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Download the PDF version: here

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References:

• Kaplan step 2 lecture notes
• Master the boards