Stella de Man - Academia.edu (original) (raw)
Papers by Stella de Man
Pediatric radiology, Jan 30, 2016
Children with severe neurological impairment and intellectual disability are prone to low bone qu... more Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This ...
Journal of human genetics, Jan 26, 2015
In 2012 Alazami et al. described a novel syndromic cause of primordial dwarfism with distinct fac... more In 2012 Alazami et al. described a novel syndromic cause of primordial dwarfism with distinct facial features and severe intellectual disability. A homozygous frameshift mutation in LARP7, a chaperone of the noncoding RNA 7SK, was discovered in patients from a single consanguineous Saudi family. To date, only one additional patient has recently been described. To further delineate the phenotype associated with LARP7 mutations, we report two additional cases originating from the Netherlands and Saudi Arabia. The patients presented with intellectual disability, distinct facial features and variable short stature. We describe their clinical features and compare them with the previously reported patients. Both cases were identified by diagnostic whole-exome sequencing, which detected two homozygous pathogenic LARP7 variants: c.1091_1094delCGGT in the Dutch case and c.1045_1051dupAAGGATA in the Saudi Arabian case. Both variants are leading to frameshifts with introduction of premature st...
Nederlands tijdschrift voor geneeskunde, 2014
In the general population osteoporosis and low impact fractures occur mainly in the elderly and i... more In the general population osteoporosis and low impact fractures occur mainly in the elderly and in people at increased risk due to disorders. In children with severe intellectual impairment and multiple disabilities severe osteoporosis and fractures of the long bones may be present from an early age. We describe a case of a 14-year-old girl with Dravet syndrome and multiple low impact fractures arising from minimal or unknown trauma. In children with severe intellectual impairment and multiple disabilities the optimizing of bone quality and peak bone mass in order to prevent osteoporosis and fractures is recommended.
Bone and Mineral, 1991
In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content ... more In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content was studied using quantitative röntgen microdensitometry (QMD) at the diaphyseal and the metaphyseal site of the left second digit. Percentile curves of bone mineral density was determined by skeletal age for boys and girls separately. Bone mineral content at the diaphyseal site was significantly associated with skeletal age, height and body weight in boys and girls and with chronological age at the metaphyseal site in boys. In girls higher levels of bone mineral content were observed in those with a skeletal age greater than 7.3 years, compared to those with a skeletal age equal to or less than 7.3 years, adjusted for height and body weight. In boys a higher level of bone mineral content was found in those with a height greater than 138 cm, adjusted for skeletal age, compared to those with a height equal or less than 130 cm, at the diaphyseal and metaphyseal site. Girls with a relatively higher body weight had lower levels of bone mineral content at the metaphyseal site.
Journal of Hypertension, 1991
In an attempt to study and prevent the development of hypertension, there is a growing interest i... more In an attempt to study and prevent the development of hypertension, there is a growing interest in measuring blood pressure in children. The aim of this is to detect and monitor those with a relatively high level of blood pressure. Until now, reference values on blood pressure in children are based on data from North-American youngsters. The present study provides percentile charts based on pooled data from studies on blood pressure conducted in six North-West European countries among 28,043 children. These blood pressure centiles are presented as age-, height- and gender-specific. Brief guidelines for blood pressure measurements in childhood and for detection of children with a relatively high blood pressure are included.
European Journal of Medical Genetics, 2007
We describe a unique family with two children having a delay in psychomotor development. In both ... more We describe a unique family with two children having a delay in psychomotor development. In both children we identified an interstitial duplication dup(2)(q34q33) using multiple, complementary molecular cytogenetic techniques. Comparative genomic hybridisation (CGH) and array-CGH were used to determine the size and the location of the duplicated region, the orientation of the duplicated region was identified with fluorescence in situ hybridisation (FISH). Both parents demonstrated a normal karyotype and normal CGH and array-CGH-profiles. However, FISH on peripheral blood cells from the mother showed the inv dup(2) in 9% of metaphases and 19% of interphase nuclei. To our knowledge this is the first report of a mosaic carrier of duplication in the long arm of chromosome 2. The finding of chromosomal mosaicism of at least 19% in the mother increases the recurrence risk. The exact characterisation of the inv dup(2) with FISH probes enabled us to offer a reliable prenatal FISH test. Comparison of the clinical features of the two children with those of previously described cases supports the hypothesis that the characteristic facial phenotype is linked to the distal part of the 2q33e q37 region. This report illustrates that in case of two sibs with an identical structural chromosomal abnormality the possibility of parental chromosomal mosaicism must be thoroughly investigated.
Developmental Medicine & Child Neurology, 2009
American Journal of Medical Genetics Part A, 2012
Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in hum... more Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.
European Journal of Medical Genetics, 2015
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormaliti... more Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotypeephenotype correlations in more detail.
Pediatric radiology, Jan 30, 2016
Children with severe neurological impairment and intellectual disability are prone to low bone qu... more Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This ...
Journal of human genetics, Jan 26, 2015
In 2012 Alazami et al. described a novel syndromic cause of primordial dwarfism with distinct fac... more In 2012 Alazami et al. described a novel syndromic cause of primordial dwarfism with distinct facial features and severe intellectual disability. A homozygous frameshift mutation in LARP7, a chaperone of the noncoding RNA 7SK, was discovered in patients from a single consanguineous Saudi family. To date, only one additional patient has recently been described. To further delineate the phenotype associated with LARP7 mutations, we report two additional cases originating from the Netherlands and Saudi Arabia. The patients presented with intellectual disability, distinct facial features and variable short stature. We describe their clinical features and compare them with the previously reported patients. Both cases were identified by diagnostic whole-exome sequencing, which detected two homozygous pathogenic LARP7 variants: c.1091_1094delCGGT in the Dutch case and c.1045_1051dupAAGGATA in the Saudi Arabian case. Both variants are leading to frameshifts with introduction of premature st...
Nederlands tijdschrift voor geneeskunde, 2014
In the general population osteoporosis and low impact fractures occur mainly in the elderly and i... more In the general population osteoporosis and low impact fractures occur mainly in the elderly and in people at increased risk due to disorders. In children with severe intellectual impairment and multiple disabilities severe osteoporosis and fractures of the long bones may be present from an early age. We describe a case of a 14-year-old girl with Dravet syndrome and multiple low impact fractures arising from minimal or unknown trauma. In children with severe intellectual impairment and multiple disabilities the optimizing of bone quality and peak bone mass in order to prevent osteoporosis and fractures is recommended.
Bone and Mineral, 1991
In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content ... more In a sample of 1190 children (574 boys and 616 girls), aged 6.8-10.7 years, bone mineral content was studied using quantitative röntgen microdensitometry (QMD) at the diaphyseal and the metaphyseal site of the left second digit. Percentile curves of bone mineral density was determined by skeletal age for boys and girls separately. Bone mineral content at the diaphyseal site was significantly associated with skeletal age, height and body weight in boys and girls and with chronological age at the metaphyseal site in boys. In girls higher levels of bone mineral content were observed in those with a skeletal age greater than 7.3 years, compared to those with a skeletal age equal to or less than 7.3 years, adjusted for height and body weight. In boys a higher level of bone mineral content was found in those with a height greater than 138 cm, adjusted for skeletal age, compared to those with a height equal or less than 130 cm, at the diaphyseal and metaphyseal site. Girls with a relatively higher body weight had lower levels of bone mineral content at the metaphyseal site.
Journal of Hypertension, 1991
In an attempt to study and prevent the development of hypertension, there is a growing interest i... more In an attempt to study and prevent the development of hypertension, there is a growing interest in measuring blood pressure in children. The aim of this is to detect and monitor those with a relatively high level of blood pressure. Until now, reference values on blood pressure in children are based on data from North-American youngsters. The present study provides percentile charts based on pooled data from studies on blood pressure conducted in six North-West European countries among 28,043 children. These blood pressure centiles are presented as age-, height- and gender-specific. Brief guidelines for blood pressure measurements in childhood and for detection of children with a relatively high blood pressure are included.
European Journal of Medical Genetics, 2007
We describe a unique family with two children having a delay in psychomotor development. In both ... more We describe a unique family with two children having a delay in psychomotor development. In both children we identified an interstitial duplication dup(2)(q34q33) using multiple, complementary molecular cytogenetic techniques. Comparative genomic hybridisation (CGH) and array-CGH were used to determine the size and the location of the duplicated region, the orientation of the duplicated region was identified with fluorescence in situ hybridisation (FISH). Both parents demonstrated a normal karyotype and normal CGH and array-CGH-profiles. However, FISH on peripheral blood cells from the mother showed the inv dup(2) in 9% of metaphases and 19% of interphase nuclei. To our knowledge this is the first report of a mosaic carrier of duplication in the long arm of chromosome 2. The finding of chromosomal mosaicism of at least 19% in the mother increases the recurrence risk. The exact characterisation of the inv dup(2) with FISH probes enabled us to offer a reliable prenatal FISH test. Comparison of the clinical features of the two children with those of previously described cases supports the hypothesis that the characteristic facial phenotype is linked to the distal part of the 2q33e q37 region. This report illustrates that in case of two sibs with an identical structural chromosomal abnormality the possibility of parental chromosomal mosaicism must be thoroughly investigated.
Developmental Medicine & Child Neurology, 2009
American Journal of Medical Genetics Part A, 2012
Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in hum... more Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.
European Journal of Medical Genetics, 2015
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormaliti... more Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotypeephenotype correlations in more detail.