Biomedical subjects

C M van Ravenswaaij-Arts

Publications and source records attributed to C M van Ravenswaaij-Arts.

11 recordsLinked to original sources

PubMed2006

Recurring HRAS mutation G12S in Dutch patients with Costello syndrome.

Costello syndrome (CS) is a rare multiple congenital anomaly/mental retardation syndrome characterized by coarse face, loose skin and cardiomyopathy. It is often associated with benign and malignant tumors. Several groups have now demonstrated that CS is caused by recurring mutations in the HRAS gene in different ethnic groups. Here, we describe three unrelated Dutch patients and show that they all have the same mutation, G12S, in HRAS. To our knowledge, our patients are the first Dutch to be analysed. The syndrome seems to be genetically homogeneous. We discuss the pertinent nosology of the syndrome.

Abnormalities, Multiple↗

PubMed2001

[From gene to disease; achondroplasia and other skeletal dysplasias due to an activating mutation in the fibroblast growth factor].

Achondroplasia, the most common and best known skeletal dysplasia, is inherited in an autosomal dominant fashion. Like a number of other skeletal dysplasias, among which hypochondroplasia and thanatophoric dysplasia, achondroplasia is caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. FGFR3 is a negative regulator of bone growth. Binding of fibroblast growth factors to the FGFR3 receptor stimulates its tyrosine kinase activity in the cell. This activates a signal transduction pathway that regulates enchondral ossification by inhibition of cell division and stimulation of cell maturation and differentiation. Mutations in the FGFR3 gene give rise to activation of the receptor in the absence of growth factors, thus causing abnormal long bone development. Position and type of mutation in the FGFR3 gene determine the extent of overactivation and thus the severity of the skeletal abnormality.

Achondroplasia↗

PubMed1999

Craniosynostosis associated with ectopia lentis in monozygotic twin sisters.

Ectopia lentis has rarely been reported to occur in association with craniosynostosis, and this was found only in sporadic cases. We report on twin sisters who underwent surgery for craniosynostosis and later on, at age 3 years, were found to have bilateral ectopia lentis. Molecular studies yielded a probability of monozygosity of more than 0.98. Inheritance of the syndrome may be autosomal dominant, possibly due to a new mutation, autosomal recessive, or X-linked with male lethality.

Abnormalities, Multiple↗

PubMed1997

Misinterpretation of trisomy 18 as a pseudomosaicism at third-trimester amniocentesis of a child with a mosaic 46,XY/47,XY, +3/48,XXY, +18 karyotype.

False-negative trisomy 18 has been reported after chorionic villus sampling, but not after amniocentesis. We describe a double aneuploidy in cultured amniocytes that was initially misinterpreted as a pseudomosaicism. A patient was referred at 31 weeks of gestation because of fetal anomalies at ultrasound examination. Karyotyping of amniocytes showed a 47,XY, +3 karyotype in 61 clones and a 48,XXY, +18 karyotype in one clone. The latter was interpreted as a pseudomosaicism, the more since a second amniocentesis revealed only cells with a 47,XY, +3 karyotype. At 36 weeks gestational age, a boy was born with congenital anomalies suggestive of trisomy 18. A blood culture showed a 48,XXY, +18 karyotype, while in fibroblasts a 47,XY, + 3/48,XXY, +18 mosaicism was found. Umbilical cord and bladder epithelial tissue also revealed normal 46,XY cells, besides the aneuploid cells. Therefore, the child proper had a 46,XY/47,XY, +3/48,XXY, +18 mosaicism with the clinical symptoms of trisomy 18. To the best of our knowledge, this is the first report of a false-negative result of trisomy 18 together with three sex chromosomes after amniocentesis.

Abnormalities, Multiple↗

PubMed1995

The influence of artificial ventilation on heart rate variability in very preterm infants.

To study the influence of artificial ventilation rate on neonatal heart rate variability (HRV), ECG and respiratory impedance curves were recorded four times a day in 20 preterm infants (< 33 wk) during the first 3 d after birth while the infants were ventilated at a wide range of ventilator rates. The contents of selected frequency bands within the R-R interval power spectrum were calculated for 3-min periods. Respiratory distress syndrome severity was assessed at each measurement. Respiratory sinus arrhythmia (RSA) induced by the ventilator appeared to mimic spontaneous RSA. As in spontaneous respiration, the amount of RSA (power in a frequency band around the respiratory rate) increases as the ventilation rate decreases. This phenomenon is most probably due to entrainment with baroreflex-related fluctuations in the heart rate. Although the artificial ventilation rate influences RSA and thus high-frequency HRV, an increase in respiratory distress syndrome severity results in a decrease in low-frequency HRV. Thus, the attenuation of low-frequency HRV by respiratory distress syndrome is not likely to be due to artificial ventilation.

Analysis of Variance↗

PubMed1993

Heart rate variability.

PURPOSE: To present an overview of the applicability of heart rate variability measurements in medicine. DATA SOURCES: During a 4-year period all new papers concerning heart rate variability were collected. A selection of the most recent publications in the presented research area was used for this review. DATA SYNTHESIS: The amount of short- and long-term variability in heart rate reflects the vagal and sympathetic function of the autonomic nervous system, respectively. Therefore heart rate variability can be used as a monitoring tool in clinical conditions with altered autonomic nervous system function. In postinfarction and diabetic patients, low heart rate variability is associated with an increased risk for sudden cardiac death. A sympathovagal imbalance is also detectable with heart rate variability analysis in coronary artery disease and essential hypertension. Besides diabetic neuropathy, in many other neurologic disorders, such as brain damage, the Guillain-Barré syndrome, and uremic neuropathy, heart rate variability analysis can provide insight into which division of the autonomic nervous system is most affected. Heart rate variability can be influenced by various groups of drugs, but it can also shed light on the mode of action of drugs. The protective effect of cardiovascular drugs in postinfarction patients has been investigated. CONCLUSIONS: Heart rate variability analysis is easily applicable in adult medicine, but physiologic influences such as age must be considered. The most important application is the surveillance of postinfarction and diabetic patients to prevent sudden cardiac death. With heart rate variability analysis, individual therapy adjustments to achieve the most favorable sympathetic-parasympathetic balance might be possible in the future.

Aging↗

PubMed1991

Influences on heart rate variability in spontaneously breathing preterm infants.

To investigate the influence of maturational and physiological factors on heart rate variability in spontaneously breathing very preterm infants (n = 29) a multiparametric study was performed during the first 3 days of life in infants born at a gestational age below 33 weeks. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Non-invasively measured blood pressure and patency of the ductus arteriosus were documented as well. Four sets of short- (STV) and long term variability (LTV) indices were calculated. Both STV and LTV appeared to be significantly influenced by conceptional and postnatal age in the appropriate for gestational age infants. LTV was influenced by the behavioural state and body movements. During state coincidence 2 ('active sleep') LTV was influenced by respiratory rate and the variations in transcutaneous PO2. An effect of blood pressure or ductus patency could not be demonstrated.

Age Factors↗

PubMed1991

The influence of respiratory distress syndrome on heart rate variability in very preterm infants.

In a multi-parametric study the influence of pathological neonatal conditions on heart rate variability was investigated in 60 preterm infants born at a gestational age below 33 weeks. Measurements were performed during the first 3 days of life. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Severity of respiratory distress syndrome (RDS), patency of ductus arteriosus and periventricular haemorrhage were documented as well. Four sets of short- (STV) and long-term variability (LTV) indices were calculated. Severe RDS was associated with a significant decrease in LTV. The influence of RDS on LTV persisted after correction for conceptional age, postnatal age, behavioural state and variations in respiratory rate and in transcutaneous PO2. Infants with a symptomatic patent ductus arteriosus had lower LTV than controls with the same severity of RDS. STV was predominantly influenced by postnatal and conceptional age, and tended to be lower in infants with periventricular haemorrhage.

Age Factors↗

PubMed1990

The influence of physiological parameters on long term heart rate variability in healthy preterm infants.

The instantaneous heart rate shows a variation around the mean heart rate caused by cardioregulatory mechanisms which are mediated through the sympathetic and vagal autonomic nervous system. To gain more insight into the influence of physiological parameters on neonatal heart rate variability a study was performed in four healthy preterm newborns during the first five days of life. Instantaneous heart rate, respiration rate, transcutaneous pO2, blood pressure and behaviour were recorded during 40 minutes four times a day. Long term heart rate variability was calculated as the difference between p95 and p5 of instantaneous heart rate values sampled during three minutes. A clear relationship between long term variability and age (maturity of the autonomic nervous system), respiration rate (respiratory sinus arrhythmia or a tidal volume mediated effect) and behaviour (increase of sympathetic tone during REM sleep) was found. No influence of blood pressure, heart rate, and transcutaneous pO2 within physiological ranges could be detected. The relative influence of the different physiological parameters on heart rate variability has to be established before the value of heart rate variability as a monitoring tool in neonatal intensive care can be investigated.

Age Factors↗

PubMed1989

Influence of behavioural state on blood pressure in preterm infants during the first 5 days of life.

The influence of behavioural state on neonatal blood pressure was studied in 19 healthy preterm infants. During the first five days of life every three hours a series of oscillometric blood pressure measurements was made. During the measurements the behavioural state was scored. The predominant states were quiet and active sleep. We confirmed the age-dependency of blood pressure with a steep increase during the first day of life. After the first day blood pressure and heart rate were slightly higher when the infant was awake than when asleep. Paired comparison (t-test) before and after spontaneous state transitions showed significant differences in median heart rate and ranges of heart rate and blood pressure, but not in median blood pressure. We conclude that especially movements influence oscillometric determination of blood pressure and heart rate.

Blood Pressure↗

PubMedDate not supplied

Localisation of the gene for a dominant congenital spinal muscular atrophy predominantly affecting the lower limbs to chromosome 12q23-q24.

Spinal muscular atrophies are a heterogeneous group of disorders. They differ in time of onset, clinical presentation, progression, severity and mode of inheritance. In 1985 a Dutch family was described with a dominant, non-progressive spinal muscular atrophy presenting at birth with arthrogryposis (MIM 600175). Linkage analysis was performed in this family. After having excluded the loci for Werdnig-Hoffmann's disease and for dominant distal spinal muscular atrophy with upper limb predominance, we were able to localise the gene to a 10 cM interval between the markers D12S78 and D12S1646 on chromosome 12q23-q24. Recently, dominant scapuloperoneal spinal muscular atrophy has been localised to an overlapping interval. However, the clinical appearances of scapuloperoneal spinal muscular atrophy and the present disorder make allelism unlikely. In 1994, a second Dutch family with a disorder similar to the present one was described. We excluded linkage to markers of the 12q23-q24 region in this family and thereby proved genetic heterogeneity of this type of dominant, congenital and nonprogressive spinal muscular atrophy.

Chromosome Mapping↗