Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association

Marco Castori, Sofia Douzgou, Evelina Silvestri, Férechté Encha-Razavi, Bruno Dallapiccola

Research output: Contribution to journalArticlepeer-review


We report on a 23-week fetus with a hypothalamic hamartoma, lobar holoprosencephaly, right anophthalmia, and facial asymmetry, features which are consistent with the boloprosencephaly-diencephalic bamartoblastoma (HDH) association. In an attempt to better delineate HDH, we reviewed 19 published patients with similar features. The HDH clinical spectrum ranges from classic holoprosencephaly with micro/anophthalmia, multiple additional findings in non-contiguous structures and early lethality, to isolated microforms of holoprosencephaly. Associated cephalic features mainly include cortical/neuronal migration defects (39%), meningeal anomalies (28%), brainstem/ posterior fossa malformations (22%), dysmorphic ears (41%), facial asymmetry (35%), and hypoplastic mandible (29%). Fifty-three percent of patients have additional extracephalic malformations, for example, vertebral/rib segmentation defects (50%), hypo/aplastic lungs (38%). congenital heart defect (29%), and urinary anomalies (29%). HDH shows etiological heterogeneity, that is, teratogenic exposure, chromosome imbalances, autosomal recessive as well as dominant "de novo" mutations. Several features could directly result from a disruptive sequence caused by an early hamartoma which alters the development of forebrain, hindbrain, meninges, and 1st-2nd branchial arches, although the pleiotropic action of genetic/environmental factors cannot be excluded. HDH does not emerge as a distinct syndrome, but other hypotheses, including separate conditions within a common pathway and the developmental field defect theory, are discussed.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number3
Publication statusPublished - Feb 1 2007


  • Blastogenesis
  • Developmental field defect
  • Etiological heterogeneity
  • Holoprosencephaly
  • Hypothalamic hamartoma
  • Sequence

ASJC Scopus subject areas

  • Genetics(clinical)


Dive into the research topics of 'Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association'. Together they form a unique fingerprint.

Cite this