Jacobsen Syndrome

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Jacobsen Syndrome

• Barry White, M.D.
• 8.23.05

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Case History

• Male infant delivered by LTCD at 39 weeks
• CD performed because of abnormal fetal
  echocardiogram
• APGAR scores of 7 and 8
• Echocardiogram showed HLHS, VSD, PFO, tricuspid
  regurgitation, mitral and aortic valve atresia,
  PDA and coarctation of aorta

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Case History

• Placed on prostaglandin E1 after birth
• CBC and CMP unremarkable except for
  thrombocytopenia (48-80,000)
• Blood drawn for cytogenetic analysis

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Physical Exam

• Hypertelorism, broad nasal ridge, trigonocephaly,
  carp-shaped upper lip, anteverted nostrils
• No poly- or syndactyly
• No cleft lip or palate
• Descended testes

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(No Transcript)
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Karyotype
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FISH
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Cytogenetic Analysis

• 46,XY,del(11)(q23.3)
• High resolution karyotype revealed a deletion of
  the long arm of chromosome 11
• This is consistent with Jacobsen Syndrome
• Also called 11q terminal deletion disorder

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Jacobsen Syndrome

• Incidence lt1/100,000
• First reported in 1973 less than 200 reported
  cases
• Most believe it is a result of a break in a
  folate-sensitive fragile site on 11q called
  FRA11B (part of CBL-2 proto-oncogene)
• Most occur de novo (only 8 by unbalanced
  inheritance)

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Jacobsen Syndrome

• Wide range of phenotypes
• growth retardation, psychomotor retardation,
  trigonocephaly, strabismus, hypertelorism, broad
  nasal bridge, anteverted nostrils, carp-shaped
  upper lip, retrognathia, low-set ears,
  camptodactyly, hammer toes, isoimmune
  thrombocytopenia, heart defects
• less commonly giant platelets, cryptorchidism,
  endocrinologic abnormalities

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Heart Defects

• About 55 have serious heart defects, including
  VSD, left sided obstructive lesions and
  abnormalities of aortic and mitral valves
• Hypoplastic left heart syndrome in approx. 5-10
  (1000-2000 times that of normal population)

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Prognostic Factors

• Significant heterogeneity in size of deletions
• Size of deletion correlates with neurocognitive
  function in most patients
• Critical regions for 14 phenotypes have been
  mapped (Grossfeld et al. 2004)
• All small deletions reported have been from
  paternal chromosome (?imprinting)

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Life Expectancy

• Largely unknown
• Most common causes of mortality are CHD and
  bleeding
• No apparent increased risk of pediatric neoplasms
  and unknown risk of adulthood neoplasms
• At least 3 tumor suppressor genes in 11q, with
  OPCML strongly linked to ovarian ca

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Outcome

• Norwood procedure was performed
• Problems with hemostasis and low oxygen
  saturation
• Now on ECMO