American Journal of Medical Genetics 3591-94 (1990)
Neonatal Progeroid Syndrome: More Than One Disease? James I. Hagadorn, William G. Wilson, W. Allen Hogge, Joseph H. Callicott, and Ernest F. Beale Department of Pediatrics, Division of Neonatology, Stanford Uniuersity, Stanford, California (J.I.H.); Departments of Pediatrics (W.G.W.,W.A.H.) and Obstetrics and Gynecology I W.A.H.), University of Virginia Health Sciences Center, Charlottesuille, and Virginia Baptist Hospital, Lynchburg, (J.H.C.,E.F.B.) Virginia
We report on an infant with the neonatal progeroid syndrome whose clinical course and autopsy findings indicate that this may be a heterogeneous phenotype. The infant had intrauterine growth retardation, absence of subcutaneous fat, and a wizened, aged face, all apparently characteristic of the condition, but also had congenital heart defects and urinary reflux not reported in previous cases. An elevated maternal serum alpha fetoprotein was noted at 16 weeks of gestation and lateonset growth retardation appeared after 31 weeks. Autopsy findings showed normal cerebral myelination, in contrast to findings of sudanophilic leukodystrophy in the one patient with the syndrome previously examined at autopsy. These findings suggest that the neonatal progeroid syndrome may be a phenotype and have more than one cause.
teristics common to all published cases, the degree of variability among them has been impressive. We report the clinical course and autopsy findings of a girl with NPS, including manifestations suggesting the possibility of clinical heterogeneity in the syndrome.
CLINICAL REPORT The patient was the 1,120 g product of a 35 week gestation, born to a 25-year-oldG2P2 white woman. An elevated maternal serum alpha fetoprotein (MSAFP)of 4.9 multiples of the median was noted at 16 weeks of gestation. Sonogram at that time showed no structural defects in the fetus, and dating parameters were consistent with menstrual age. Amniotic fluid AFP was normal, and chromosomes of cultured amniotic fluid fibroblasts were normal (46,XX). At 31 weeks, repeat sonographic evaluation showed apparently normal interim fetal growth and no structural malformations. However, a t 34 weeks ultrasonography showed severe oligohydramnios and symmetrical intrauterine growth KEY WORDS: Wiedemann-Rautenstrauch retardation. Premature onset of labor at 35 weeks with syndrome, progeria, matersevere fetal heart rate decelerations prompted emernal serum alpha fetoprogency cesarean section. tein, sudanophilic leukoAt hysterotomy the patient was found in a transverse dystrophy lie without amniotic fluid, with abnormal appearance and severe growth retardation. The umbilical cord had 3 vessels but was hemorrhagic at the base, and the plaINTRODUCTION centa showed multiple infarcts. Apgar scores were 8 and The neonatal progeroid syndrome (NPS), charac- 9 at one and 5 minutes, respectively. The patient apterized principally by intrauterine and postnatal peared to be in no distress, and had stable blood glucose growth failure, congenital facial appearance similar to and respiratory function. However, she developed abthat seen in older children with progeria, and virtual dominal distention shortly after birth, and was oliguric absence of subcutaneous fat, is an uncommon disorder; during the first 24 hours of life. A nasogastric tube was to date 6 cases have been reported in Europe [Rau- placed, from which bilious fluid drained. Abdominal tenstrauch et al., 1977; Wiedemann, 1979; Devos et al., sonography showed dilatation of the renal pelves and 1981; Snigula and Rautenstrauch, 1981; Martin et al., calyces, with no evidence of acute gastrointestinal ob1984;Rudin et al., 19881and one in Japan [Ohashi et al., struction. She was transferred to the University of Vir19871. While there are a number of distinctive charac- ginia Medical Center for evaluation and further management. On arrival the patient was an emaciated, small-forgestational-age, premature, white female, with apparReceived for publication March 9, 1989; revision received July ent generalized absence of subcutaneous fat and an ab21, 1989. Address reprint requests to William G. Wilson, M.D., Depart- normal, aged appearance (Fig. 1).Her weight was 1,090 ment of Pediatrics, Box 386 University of Virginia Health Sciences g (
Neonatal Progeroid Syndrome: More Than One Disease? James I. Hagadorn, William G. Wilson, W. Allen Hogge, Joseph H. Callicott, and Ernest F. Beale Department of Pediatrics, Division of Neonatology, Stanford Uniuersity, Stanford, California (J.I.H.); Departments of Pediatrics (W.G.W.,W.A.H.) and Obstetrics and Gynecology I W.A.H.), University of Virginia Health Sciences Center, Charlottesuille, and Virginia Baptist Hospital, Lynchburg, (J.H.C.,E.F.B.) Virginia
We report on an infant with the neonatal progeroid syndrome whose clinical course and autopsy findings indicate that this may be a heterogeneous phenotype. The infant had intrauterine growth retardation, absence of subcutaneous fat, and a wizened, aged face, all apparently characteristic of the condition, but also had congenital heart defects and urinary reflux not reported in previous cases. An elevated maternal serum alpha fetoprotein was noted at 16 weeks of gestation and lateonset growth retardation appeared after 31 weeks. Autopsy findings showed normal cerebral myelination, in contrast to findings of sudanophilic leukodystrophy in the one patient with the syndrome previously examined at autopsy. These findings suggest that the neonatal progeroid syndrome may be a phenotype and have more than one cause.
teristics common to all published cases, the degree of variability among them has been impressive. We report the clinical course and autopsy findings of a girl with NPS, including manifestations suggesting the possibility of clinical heterogeneity in the syndrome.
CLINICAL REPORT The patient was the 1,120 g product of a 35 week gestation, born to a 25-year-oldG2P2 white woman. An elevated maternal serum alpha fetoprotein (MSAFP)of 4.9 multiples of the median was noted at 16 weeks of gestation. Sonogram at that time showed no structural defects in the fetus, and dating parameters were consistent with menstrual age. Amniotic fluid AFP was normal, and chromosomes of cultured amniotic fluid fibroblasts were normal (46,XX). At 31 weeks, repeat sonographic evaluation showed apparently normal interim fetal growth and no structural malformations. However, a t 34 weeks ultrasonography showed severe oligohydramnios and symmetrical intrauterine growth KEY WORDS: Wiedemann-Rautenstrauch retardation. Premature onset of labor at 35 weeks with syndrome, progeria, matersevere fetal heart rate decelerations prompted emernal serum alpha fetoprogency cesarean section. tein, sudanophilic leukoAt hysterotomy the patient was found in a transverse dystrophy lie without amniotic fluid, with abnormal appearance and severe growth retardation. The umbilical cord had 3 vessels but was hemorrhagic at the base, and the plaINTRODUCTION centa showed multiple infarcts. Apgar scores were 8 and The neonatal progeroid syndrome (NPS), charac- 9 at one and 5 minutes, respectively. The patient apterized principally by intrauterine and postnatal peared to be in no distress, and had stable blood glucose growth failure, congenital facial appearance similar to and respiratory function. However, she developed abthat seen in older children with progeria, and virtual dominal distention shortly after birth, and was oliguric absence of subcutaneous fat, is an uncommon disorder; during the first 24 hours of life. A nasogastric tube was to date 6 cases have been reported in Europe [Rau- placed, from which bilious fluid drained. Abdominal tenstrauch et al., 1977; Wiedemann, 1979; Devos et al., sonography showed dilatation of the renal pelves and 1981; Snigula and Rautenstrauch, 1981; Martin et al., calyces, with no evidence of acute gastrointestinal ob1984;Rudin et al., 19881and one in Japan [Ohashi et al., struction. She was transferred to the University of Vir19871. While there are a number of distinctive charac- ginia Medical Center for evaluation and further management. On arrival the patient was an emaciated, small-forgestational-age, premature, white female, with apparReceived for publication March 9, 1989; revision received July ent generalized absence of subcutaneous fat and an ab21, 1989. Address reprint requests to William G. Wilson, M.D., Depart- normal, aged appearance (Fig. 1).Her weight was 1,090 ment of Pediatrics, Box 386 University of Virginia Health Sciences g (
