Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified.
In a population of 27 flemish newborns with subgaleal bleeding encountered within a period of 6 years, we studied the obstetrical, clinical and radiological data. In contrast with controversial findings from the available literature, there is little doubt that difficult, often elective vacuum extraction is the main cause of this neonatal emergency. Disturbances in haemostasis, when documented, were attributed to focal intrahaematoma consumption, except for one boy who presented with haemophilia and neonatal subgaleal bleeding. Conventional X-ray examination continues to be of importance for the documentation of suture diastasis, fissures and fractures. CT scan reveals both the amount of extra-osseous bleeding, the degree of bone displacement and injury as well as the type and extent of associated intracranial damage. Subgaleal haemorrhage rarely hides a growing synchrondrosal rupture.
Unilateral thalamic bleeding with associated intraventricular hemorrhage is reported in three full-term neonates. The first presented within 48 hours from birth with early onset streptococcal meningitis, persistent pulmonary hypertension, tonic seizures and a tense fontanelle. The second presented 6 days after birth with irritability, opisthotonus, a tense fontanelle and tonic seizures. The third was admitted three days after birth with seizures and a tense fontanelle. In the latter two infants NMR and CT imaging documented thrombosed superficial and deep cerebral veins. The etiopathogenesis of intracranial venous thrombosis in the neonate is diverse: asphyxia, dehydration, polycythemia, sepsis-meningitis and difficult delivery are the main causes. In one of our patients jugular vein compression by the collar of a negative-pressure ventilation chamber probably initiated the intracranial events. More than half of the survivors sustain severe neurological impairment.
Ischaemia within the regions supplied by vertebral and posterior cerebral arteries has been described as a complication of birth injury, either by direct trauma or by compression from a herniated temporal uncus. Ischaemia within the territory of the middle cerebral artery has been documented after a stretch injury of the vessel's elastica interna. From a series of seven personal observations on birth trauma and related cerebral stroke, we describe three neonates with the uncal herniation type of occipital stroke and four infants with hypoperfusion of the middle cerebral artery or one of its major branches. In three of the latter a basal convexity subdural haemorrhage probably induced the ischaemia, whereas in the other it was associated with haemorrhagic contusion of the parietal lobe.Experimental work and reports on older children support the idea that vasospasm due to surrounding extravasated blood can be one of the responsible mechanisms. Both forceps delivery and difficult vacuum extraction can be implicated in this supratentorial injury , leading to permanent neurological damage in at least half of the survivors in this series.
SUMMARY Two neonates who went. into acute hypovolaemic shock due to a tight nuchal cord were successfully resuscitated. The occurrence of this life threatening complication in two low risk pregnancies emphasises the importance of having staff trained in resuscitation immediately available in the delivery unit. The infant was extremely hypotonic and pale, with a tachycardia. The peripheral pulses were weak, and there were signs of poor capillary perfusion. There was no oedema or splenohepatomegaly. Five minutes after birth the pH of the infant's blood was 7 05. He was immediately intubated and 50 ml of plasma given through a venous umbilical catheter in the delivery room. Shortly afterwards 75 ml of whole blood was transfused because of the suspicion of acute fetal blood loss. Venous haematocrit before the blood transfusion was 33%. Examination of a peripheral blood smear showed a normochromic normocytic anaemia (haemoglobin concentration 90 g/l) without normoblastosis. A few hours after the blood transfusion the child was extubated and 48 hours later he was transferred to the postnatal ward, from which he was discharged in good health when 6 days old.In this case there was no fetomaternal blood group incompatibility and the direct Coombs' test was negative. The placenta (700 g) and the umbilical cord (length 42 cm) were normaL Cord insertion was paramarginal without aberrant vessels. Fetal membranes were complete and there were no blood. clots on the maternal surface of the placenta. Fetomaternal transfusion was excluded because the Kleihauer test performed six hours after delivery was negative. The infant had no signs of external or internal haemorrhage. Ultrasound and computed tomography scans of the brain and abdominal ultrasound examination yielded normal results. CASE 2 A baby boy weighing 3010 g was born at a gestational age of 38 weeks. The mother was 29 years old, healthy, normotensive and multiparous. The cervix was softened by extra-amniotic instillation of prostaglandin E2 gel, and low amniotomy was performed two hours before delivery. The liquor was clear. Epidural anaesthesia (12 ml 0-25% bupivacaine for one hour) was started during labour and blood pressure remained normal. The second stage was augmented with oxytocin (6 mU/minute). Internal monitoring showed early (type I) and late (type II) decelerations. Five minutes before birth the pH of the scalp blood was 7-31. The infant's head was delivered easily by ventouse but the neck was tightly entangled by two loops of cord. Because the nuchal cord could not be reduced early clamping and cutting were necessary for full delivery. Apgar scores were 4 and 6 after one and five minutes, respectively. The umbilical arterial pH was 7 05.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.