Our group recently described a 23-week fetus with the association of holoprosencephaly-diencephalic hamortoblastoma (HDH) and reviewed the literature, identifying 19 additional patients with similar features. Both clinical and etiological heterogeneity were outlined, thus suggesting that HDH could indeed represent an overlapping phenotype of separate conditions, perhaps within a common morphogenetic pathway. In pathogenetic perspective, we hypothesized that the cause(s) for HDH may act early in gestation, probably during blastogenesis [Castori et al., 2007].We had an opportunity to evaluate an additional fetus with HDH, born to a G1P0 36-year-old woman and a 33-year-old man. Family history was unremarkable. Following ultrasound detection of alobar holoprosencephaly (HPE) and severe IUGR, transabdominal amniocentesis performed at 17 weeks demonstrated a 69,XXX fetal karyotype. Pregnancy was terminated at 19 weeks. Physical examination showed a female fetus with a weight of 108 g (<3rd centile); crown-rump length, 13 cm; crown-heel length, 19 cm (<3rd centile); and head circumference, 13 cm (<3rd centile), suggestive of apparently symmetric growth restriction. Facial abnormalities included upslanting palpebral fissures, apparently low-set ears, premaxillary agenesis, ankyloglossia, retrognathia, and mild nuchal edema (Fig. 1A,B). Bilateral III-IV finger and II-V toe syndactyly, stubby great toe on the left, and sandal gap of the right foot were also evident ( Fig. 1C-E). Necropsy findings comprised ostium secundum type interatrial septal defect, ventricular septal defect, ''horseshoe'' kidneys with cystic dysplastic disease of the fused inferior poles, and hypoplastic adrenal glands. The placenta was small (29 g, <3rd centile) with multiple calcifications and had no sign of hydatiform degeneration. Brain dissection showed alobar HPE with a single ventricle and the absence of the falx cerebri, corpus callosum, septum pellucidum, and olfactory tracts and bulbs. Both thalami were substituted by a mass extending over the optic chiasm and the right optic nerve (Fig. 2A). Microscopically, this mass was composed of disorganized relatively mature neurons, glial cells, ependymal elements, and vessels, without any cytological atypia (Fig. 2B,C). These findings were consistent with hypothalamic hamartoma (HH). The eyes were normally formed and histologic examination showed bilateral retinal dysplasia, manifested by numerous rosettes and minimal gliosis (Fig. 2D). Neuronal migration defects and other histological abnormalities were excluded. A radiographic survey confirmed limb anomalies and
