Abstract
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 language | English |
|---|---|
| Pages (from-to) | 277-284 |
| Number of pages | 8 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 143 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 1 2007 |
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Keywords
- Blastogenesis
- Developmental field defect
- Etiological heterogeneity
- Holoprosencephaly
- Hypothalamic hamartoma
- Sequence
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association. / Castori, Marco; Douzgou, Sofia; Silvestri, Evelina; Encha-Razavi, Férechté; Dallapiccola, Bruno.
In: American Journal of Medical Genetics, Part A, Vol. 143, No. 3, 01.02.2007, p. 277-284.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association
AU - Castori, Marco
AU - Douzgou, Sofia
AU - Silvestri, Evelina
AU - Encha-Razavi, Férechté
AU - Dallapiccola, Bruno
PY - 2007/2/1
Y1 - 2007/2/1
N2 - 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.
AB - 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.
KW - Blastogenesis
KW - Developmental field defect
KW - Etiological heterogeneity
KW - Holoprosencephaly
KW - Hypothalamic hamartoma
KW - Sequence
UR - http://www.scopus.com/inward/record.url?scp=33846815360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846815360&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.31591
DO - 10.1002/ajmg.a.31591
M3 - Article
C2 - 17230485
AN - SCOPUS:33846815360
VL - 143
SP - 277
EP - 284
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -