Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association.
We report on a 23-week fetus with a hypothalamic hamartoma, lobar holoprosencephaly, right anophthalmia, and facial asymmetry, features which are consistent with the holoprosencephaly-diencephalic hamartoblastoma (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 extra-cephalic 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.
Castori
Marco
M
IRCCS-C.S.S. San Giovanni Rotondo and C.S.S.-Mendel Institute, Rome, Italy.
Douzgou
Sofia
S
Silvestri
Evelina
E
Encha-Razavi
Férechté
F
Dallapiccola
Bruno
B
D000015:Abnormalities, Multiple; D000025:Abortion, Eugenic; D000328:Adult; D001927:Brain Diseases / Q000150:complications / Q000151:congenital / Q000175:diagnosis*; D005260:Female; D005315:Fetal Diseases / Q000473:pathology; D006222:Hamartoma / Q000150:complications* / Q000175:diagnosis*; D016142:Holoprosencephaly / Q000150:complications* / Q000175:diagnosis*; D006801:Humans; D011247:Pregnancy