We report on congenital hypothalamic hamartomas, discovered at autopsy in 3 unrelated fetuses. In the first 2 patients, the tumor was associated with skeletal dysplasia only. In the third patient, it was part of a non-random congenital malformation association, suggestive of Meckel syndrome. In one family, a previous boy died soon after birth with similar craniofacial and skeletal abnormalities. As far as we know, the association between isolated skeletal dysplasia and congenital hypothalamic hamartomas has not yet been documented in the literature. Nevertheless, a spectrum of skeletal abnormalities has been described in association with congenital hypothalamic "hamartoblastoma" and a constellation of variable visceral malformations under the eponym of "Pallister-Hall syndrome" (PHS). A detailed analysis of the PHS reported cases shows that only skeletal dysplasia and oro-facial abnormalities are present constantly. They show similarities with those found in our first 2 cases. These findings prompt us to consider skeletal dysplasia and oro-facial abnormalities as common denominator and minimum criteria required to define a nosologically distinct, possibly familial entity, which we suggest calling "congenital hypothalamic hamartoma syndrome" (CHHS).

In this study, fetal growth velocities of the body weight, crown-heel length, crown-rump length and head circumference were established from 478 normal fetuses and neonates, aged 8–41 gestational weeks. The growth rates were computed by time intervals, and the velocity curves were plotted with their 95% confidence intervals. The body weight displayed an accelerating pattern of growth until 34–35 weeks and a breakdown of the growth rate afterwards, as we already observed for the brain weight in another study published in Biology of the Neonate. Decreasing patterns of growth velocity throughout pregnancy were observed for the crown-heel and the crown-rump lengths, with a marked fall at 35 weeks. The growth velocity curve of the head circumference is also decreasing, but in a more irregular way. A curious revival of growth velocity was observed in most parameters at about 38 weeks. These changes in the growth rhythm were similar to those found previously with ultrasound data.

Two sets of siblings, in two different families, presenting with congenital and progressive neurological disorders, cerebral calcifications and leukodystrophy are reported. In the first family, the diagnosis of brain calcifications in two infants was based on skull X-rays; in the second family, ultrasound scans showed hyperechoic areas in the basal ganglia and periventricular white matter in both infants. Neuropathological studies confirmed the calcifications and revealed severe abnormalities of the white matter with GFAP positive gliosis. Electron micrographs showed large astrocytes with an increased amount of glial filaments. In the group of idiopathic non arteriosclerotic cerebral calcifications, these four cases may represent a separate entity with possible autosomal recessive inheritance.

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