title: Giant diencephalic harmartoma and related anomalies: a newly recognized entity distinct from the Pallister-Hall syndrome.
abstract: 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.
authors.affiliation: Department of Developmental Biology, AP-HP- Robert Debré Hospital, Denis Diderot University, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Guimiot
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.forename: Georges
authors.initials: G
authors.lastname: Bonyhay
authors.forename: Sophie
authors.initials: S
authors.lastname: Patrier
authors.forename: Françoise
authors.initials: F
authors.lastname: Menez
authors.forename: Valérie
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: Valentine
authors.initials: V
authors.lastname: Icowick
authors.forename: Danièle
authors.initials: D
authors.lastname: Eurin
authors.forename: Catherine
authors.initials: C
authors.lastname: Garel
authors.forename: Hélène
authors.initials: H
authors.lastname: Moirot
authors.forename: Eric
authors.initials: E
authors.lastname: Verspyck
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: Olivier
authors.initials: O
authors.lastname: Picone
authors.forename: Jean François
authors.initials: JF
authors.lastname: Oury
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Anne Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000028:Abortion, Induced; D000328:Adult; D004027:Diencephalon / Q000473:pathology*; D019066:Facies; D005260:Female; D005865:Gestational Age; D006222:Hamartoma / Q000235:genetics*; D006801:Humans; D054975:Pallister-Hall Syndrome; D011247:Pregnancy; D013577:Syndrome; D016216:Ultrasonography, Prenatal