Premium
Giant diencephalic harmartoma and related anomalies: A newly recognized entity distinct from the Pallister–Hall syndrome
Author(s) -
Guimiot Fabien,
Marcorelles Pascale,
Aboura Azzedine,
Bonyhay Georges,
Patrier Sophie,
Menez Françoise,
DrouinGarraud Valérie,
Icowick Valentine,
Eurin Danièle,
Garel Catherine,
Moirot Hélène,
Verspyck Eric,
SaugierVeber Pascale,
AttieBitach Tania,
Picone Olivier,
Oury Jean François,
Verloes Alain,
Delezoide Anne Lise,
Laquerrière Pr. Annie
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32859
Subject(s) - hypothalamic hamartoma , hamartoma , holoprosencephaly , anatomy , aborted fetus , pathology , gli3 , lesion , polydactyly , dysgenesis , fetus , biology , diencephalon , medicine , central nervous system , endocrinology , precocious puberty , pregnancy , genetics , repressor , hormone , transcription factor , gene , biochemistry
An hypothalamic hamartoma is an abnormal mass of mature glio‐neuronal tissue present in the hypothalamic area. It usually measures <2 cm of diameter. Most of the time, this hamartoma occurs in Pallister–Hall syndrome (PHS), due to heterozygous GLI3 mutations. We report on five fetuses with giant diencephalic hamartoma and other midline brain and facial malformations, without mutation in the GLI3 gene or genomic rearrangements in three of them. The fetuses showed facial asymmetry, unilateral ear and eye anomalies, and facial cleft. Extracephalic malformations consisted of vertebral anomalies and short nails, without polydactyly and cardiac malformation. The diencephalon was replaced by an encephaloid mass protruding into the facial cleft. Normal cerebral structures were not detectable. In one patient, holoprosencephaly of the syntelencephalic type was noted. Arhinencephaly was present in all patients. Histologically, the ill‐defined, multilobulated lesion was made of neuroblastic and neurocytic cell foci, lying in a fibrillar network, elaborating sometimes perivascular pseudorosettes, with a maturation gradient in accordance with the fetal age. Owing to their location, the tumors could be described as diencephalic, rather than hypothalamic hamartomas. The striking asymmetry of the facial anomalies and the diencephalic malformations are not in the spectrum observed with PHS and related syndromes, suggesting a distinct entity involving abnormal morphogenetic developmental fields at around 5 weeks of gestation. © 2009 Wiley‐Liss, Inc.