The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

No abstract

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

No abstract

Mechanisms of endothelium-dependent regulation of cerebral circulation in human neonates are poorly understood owing to the lack of experimental data. Prostanoids, the products of the cyclooxygenase (COX) pathway, appear to be important regulators of blood flow in neonates. COX activity in cultured endothelial cells from small (60 -300 m) and large (Ͼ300 m) microvessels from the autopsy specimens of neonatal human cerebral cortex and cerebellum (22-26 wk gestational age) was detected as production of vasodilator prostanoids, prostacyclin [as 6-keto-prostaglandin (PG) F 1␣ ] and PGE 2 from arachidonic acid. Treatment of neonatal human cerebral microvascular endothelial cells (hCMVEC) with IL-1␤ (50 ng/mL, 17 h) stimulated COX activity 5-to 20-fold. Basal and IL-1␤-stimulated COX activities were inhibited by NS-398, indicating substantial COX-2 contribution to endothelial prostanoid synthesis in neonatal human brain cortex and cerebellum at rest and when mimicking the inflammatory conditions. Increased COX-2-linked activity in response to IL-1␤ was observed in hCMVEC from both cerebrum and cerebellum (5-to 20-fold), while under the same conditions elevated COX-1-linked activity was detected only in hCMVEC from cerebellum (5-to 10-fold). In IL-1␤-treated hCMVEC, a shift toward PGE 2 as the major vasodilator product of the COX pathway was observed. Acute treatment with the protein tyrosine kinase inhibitor, tyrphostin 25, inhibited basal and IL-1␤-induced COX activities, suggesting the importance of posttranslational modifications in endothelial COX-2 activation in human brain. Altogether, these data indicate that both COX-1 and COX-2 contribute to endothelial prostanoid synthesis in the neonatal human brain under basal conditions and in response to proinflammatory cytokine IL-1␤. Cerebral circulatory disorders produce serious complications in human neonates, such as cerebral hemorrhages and hypoxicischemic injuries, that can result in life-long neurologic dysfunction in survivors including cerebral palsy, epilepsy, and mental retardation. Mechanisms of the regulation of cerebral circulation in neonates are understood incompletely, and experimental data are very limited. Vascular endothelium-derived dilator prostanoids, NO, and carbon monoxide are vasorelaxant factors essential in the regulation of cerebral blood flow. There are speciesspecific and age-dependent differences in physiologically relevant endothelial vasorelaxants in the cerebral circulation (1). In human newborns, prostanoids appear to be major factors that contribute to regulation of cerebral blood flow in response to hypercapnia, asphyxia, ischemia, and cerebral hemorrhage (1-3), and indomethacin is widely used in neonatal practice (2,4,5). Similarly, in newborn pigs, prostanoids contribute to the regulation of cerebral blood flow under basal conditions and in response to physiologically important stimuli, such as CO 2 , oxygen, and changes in blood pressure (1). Prostanoids are also important in the pathogenesis of inflammation because they alter in...