Els Leenheer | Ghent University (original) (raw)

Papers by Els Leenheer

Research paper thumbnail of Long-term anatomic and functional outcome of pediatric myringoplasty in primary and revision cases

International Journal of Pediatric Otorhinolaryngology

Research paper thumbnail of Vestibular Infant Screening–Flanders: What is the Most Appropriate Vestibular Screening Tool in Hearing-Impaired Children?

Research paper thumbnail of Predicting Early Vestibular and Motor Function in Congenital Cytomegalovirus Infection

Research paper thumbnail of Long-Term Neurodevelopmental Outcome in Children with Congenital Cytomegalovirus Infection: A Prospective Multicenter Cohort Study

Research paper thumbnail of Aetiologies after newborn hearing screening

Research paper thumbnail of Variants affecting diverse domains of MEPE are associated with two distinct bone disorders, a craniofacial bone defect and otosclerosis

Genetics in medicine : official journal of the American College of Medical Genetics, Jan 5, 2018

To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP)... more To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis. We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls. Exome sequencing in the HCFP family led to the identification of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. As the HL phenotype in this family resembled otosclerosis, we performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060). MEPE exerts its function in bone homeostasis by two domains, an RGD and an acidic serine aspartate-rich MEPE-associat...

Research paper thumbnail of Motorische prestatie en vestibulaire functie bij kinderen gediagnostiseerd met een congenitale cytomegalovirus (cCMV) infectie of een connexine 26 (Cx26) mutatie

Research paper thumbnail of Hearing loss and congenital CMV infection: a systematic review

Pediatrics, 2014

Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. To... more Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41-0.79). Among these newborns 12.6% (95% confidence interval, 10.2-16.5) wil...

Research paper thumbnail of Vestibular function and motor performance in infants with congenital cytomegalovirus infection: a preliminary study

Research paper thumbnail of Audiologic and genetic characterization of hearing loss in Osteogenesis Imperfecta

Research paper thumbnail of Etiological approach in unidentified hearing loss suggestive of a genetic cause

B-ent, 2014

Introduction and aim Etiological diagnosis of hearing impairment is of great importance to ensure... more Introduction and aim Etiological diagnosis of hearing impairment is of great importance to ensure early and adequate management. Several diagnostic tests can be used to reach this goal (history taking, physical examination, imaging, laboratory tests,...). However, clear guidelines about optimal implementation and sequence of these tests are required. The purpose of this study was to optimize the etiological-diagnostic work-up of unidentified hearing loss.

Research paper thumbnail of Further delineation of the auditory phenotype in Stickler syndrome

Research paper thumbnail of Diagnostic criteria for Stickler syndrome based on comprehensive clinical and molecular analysis

Stickler syndrome is a heterogeneous disorder variably affecting the ocular, orofacial, auditory ... more Stickler syndrome is a heterogeneous disorder variably affecting the ocular, orofacial, auditory and skeletal system. Mutations in COL2A1, COL11A1 and COL11A2 have been found to cause Stickler syndrome and result in slightly distinct phenotypes, referred to as type 1, type 2 and type 3 respectively. Due to the large phenotypic variability, no consensus about minimal clinical diagnostic criteria exists. Currently, diagnosis is mainly based on expert opinion and positive mutation analysis. The aim of this study is to better define the syndrome and its different types by creating clinically-based guidelines. Medical records of more than 250 probands with a clinical suspicion of Stickler syndrome were reviewed for relevant symptoms and molecular results. COL2A1 analysis was performed in all patients, and COL11A1 and COL11A2 were subsequently analyzed in the COL2A1-negative patients. In 90% of the probands, the disease-causing mutation was detected, of which 82% was located in the COL2A1...

Research paper thumbnail of Audiological and vestibular findings in congenital cytomegalovirus infection: results of a prospective cohort study

Research paper thumbnail of Audiologic and genetic determination of hearing loss in osteogenesis imperfecta

Research paper thumbnail of Novel COL11A1 mutations in Stickler syndrome detected by next-generation sequencing

Stickler syndrome is a connective tissue disorder with considerable phenotypic and genotypic vari... more Stickler syndrome is a connective tissue disorder with considerable phenotypic and genotypic variability, characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint problems. Up to now, mutations in 5 different collagen genes have been associated with the disease. Mutations in the COL11A1 gene may result in Stickler syndrome type 2, which can be differentiated clinically by a ‘beaded’ vitreous and a more severe hearing loss compared to the more prevalent type 1, caused by mutations in COL2A1. In literature, only a few dozen COL11A1 mutations have been reported. We selected 33 unrelated COL2A1 mutation-negative patients, based on their clinical features, for molecular COL11A1 analysis, by means of next-generation sequencing technology (MiSeq, Illumina). The bioinformatic pipeline included the CLC bio Workbench 6.0 followed by an in-house developed software package for variant interpretation. Assays lacking sufficient coverage as well as the mutations ...

Research paper thumbnail of Motor performance and vestibular function in children diagnosed with congenital cytomegalovirus (cCMV) infection or connexin 26 (Cx26) mutation

Research paper thumbnail of Effect of MRI on distortion product otoacoustic emissions in neonates : a pilot study

Research paper thumbnail of Hearing impairment in children with Stickler syndrome: review of phenotype and correlation with genotype

Research paper thumbnail of Cranial ultrasound and MRI: complementary or not in the diagnostic assessment of children with congenital CMV infection?

European Journal of Pediatrics

Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both ... more Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both a place in the assessment of children with congenital cytomegalovirus infection (cCMV) remains a topic of discussion between research groups. Literature suggests that MRI is indicated only in children with abnormal crUS. In Flanders, Belgium, combined crUS and MRI was performed on 639 children with cCMV, referred for diagnostic assessment. Cranial US was classified as abnormal in the presence of striatal vasculopathy, calcifications, cysts, cystic germinolysis, and/or ventriculomegaly. MRI findings were classified as abnormal in the presence of gyration disorders, cerebellar abnormalities, ventriculomegaly, cysts, or pathologic white matter lesions. One in five children (93/480) with normal crUS showed abnormal findings on MRI. Of them, 85 (91.4%) were classified as symptomatic. In 37 of those 93 children (39.8%), classification as severely symptomatic was made based on MRI lesions alone. MRI and crUS proved to be complementary in the assessment of CNS involvement in children with cCMV. Long-term studies are needed to evaluate the importance of this finding with respect to outcome and benefit of therapy in this particular subgroup of patients with cCMV infection. Conclusion: Our findings support an enhanced role of MRI in the diagnosis of CNS involvement in children with cCMV infection. The ideal assessment should include both imaging techniques, as the strengths of each test compensate for the other’s weaknesses. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV.

Research paper thumbnail of Long-term anatomic and functional outcome of pediatric myringoplasty in primary and revision cases

International Journal of Pediatric Otorhinolaryngology

Research paper thumbnail of Vestibular Infant Screening–Flanders: What is the Most Appropriate Vestibular Screening Tool in Hearing-Impaired Children?

Research paper thumbnail of Predicting Early Vestibular and Motor Function in Congenital Cytomegalovirus Infection

Research paper thumbnail of Long-Term Neurodevelopmental Outcome in Children with Congenital Cytomegalovirus Infection: A Prospective Multicenter Cohort Study

Research paper thumbnail of Aetiologies after newborn hearing screening

Research paper thumbnail of Variants affecting diverse domains of MEPE are associated with two distinct bone disorders, a craniofacial bone defect and otosclerosis

Genetics in medicine : official journal of the American College of Medical Genetics, Jan 5, 2018

To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP)... more To characterize new molecular factors implicated in a hereditary congenital facial paresis (HCFP) family and otosclerosis. We performed exome sequencing in a four-generation family presenting nonprogressive HCFP and mixed hearing loss (HL). MEPE was analyzed using either Sanger sequencing or molecular inversion probes combined with massive parallel sequencing in 89 otosclerosis families, 1604 unrelated affected subjects, and 1538 unscreened controls. Exome sequencing in the HCFP family led to the identification of a rare segregating heterozygous frameshift variant p.(Gln425Lysfs*38) in MEPE. As the HL phenotype in this family resembled otosclerosis, we performed variant burden and variance components analyses in a large otosclerosis cohort and demonstrated that nonsense and frameshift MEPE variants were significantly enriched in affected subjects (p = 0.0006-0.0060). MEPE exerts its function in bone homeostasis by two domains, an RGD and an acidic serine aspartate-rich MEPE-associat...

Research paper thumbnail of Motorische prestatie en vestibulaire functie bij kinderen gediagnostiseerd met een congenitale cytomegalovirus (cCMV) infectie of een connexine 26 (Cx26) mutatie

Research paper thumbnail of Hearing loss and congenital CMV infection: a systematic review

Pediatrics, 2014

Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. To... more Hearing loss caused by congenital cytomegalovirus (cCMV) infection was first observed in 1964. Today cCMV is the most common cause of nonhereditary sensorineural hearing loss in childhood. Our objective was to provide an overview of the prevalence of cCMV-related hearing loss, to better define the nature of cCMV-associated hearing loss, and to investigate the importance of cCMV infection in hearing-impaired children. Two reviewers independently used Medline and manual searches of references from eligible studies and review articles to select cohort studies on children with cCMV infection with audiological follow-up and extracted data on population characteristics and hearing outcomes. Thirty-seven studies were included: 10 population-based natural history studies, 14 longitudinal cohort studies, and 13 retrospective studies. The prevalence of cCMV in developed countries is 0.58% (95% confidence interval, 0.41-0.79). Among these newborns 12.6% (95% confidence interval, 10.2-16.5) wil...

Research paper thumbnail of Vestibular function and motor performance in infants with congenital cytomegalovirus infection: a preliminary study

Research paper thumbnail of Audiologic and genetic characterization of hearing loss in Osteogenesis Imperfecta

Research paper thumbnail of Etiological approach in unidentified hearing loss suggestive of a genetic cause

B-ent, 2014

Introduction and aim Etiological diagnosis of hearing impairment is of great importance to ensure... more Introduction and aim Etiological diagnosis of hearing impairment is of great importance to ensure early and adequate management. Several diagnostic tests can be used to reach this goal (history taking, physical examination, imaging, laboratory tests,...). However, clear guidelines about optimal implementation and sequence of these tests are required. The purpose of this study was to optimize the etiological-diagnostic work-up of unidentified hearing loss.

Research paper thumbnail of Further delineation of the auditory phenotype in Stickler syndrome

Research paper thumbnail of Diagnostic criteria for Stickler syndrome based on comprehensive clinical and molecular analysis

Stickler syndrome is a heterogeneous disorder variably affecting the ocular, orofacial, auditory ... more Stickler syndrome is a heterogeneous disorder variably affecting the ocular, orofacial, auditory and skeletal system. Mutations in COL2A1, COL11A1 and COL11A2 have been found to cause Stickler syndrome and result in slightly distinct phenotypes, referred to as type 1, type 2 and type 3 respectively. Due to the large phenotypic variability, no consensus about minimal clinical diagnostic criteria exists. Currently, diagnosis is mainly based on expert opinion and positive mutation analysis. The aim of this study is to better define the syndrome and its different types by creating clinically-based guidelines. Medical records of more than 250 probands with a clinical suspicion of Stickler syndrome were reviewed for relevant symptoms and molecular results. COL2A1 analysis was performed in all patients, and COL11A1 and COL11A2 were subsequently analyzed in the COL2A1-negative patients. In 90% of the probands, the disease-causing mutation was detected, of which 82% was located in the COL2A1...

Research paper thumbnail of Audiological and vestibular findings in congenital cytomegalovirus infection: results of a prospective cohort study

Research paper thumbnail of Audiologic and genetic determination of hearing loss in osteogenesis imperfecta

Research paper thumbnail of Novel COL11A1 mutations in Stickler syndrome detected by next-generation sequencing

Stickler syndrome is a connective tissue disorder with considerable phenotypic and genotypic vari... more Stickler syndrome is a connective tissue disorder with considerable phenotypic and genotypic variability, characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint problems. Up to now, mutations in 5 different collagen genes have been associated with the disease. Mutations in the COL11A1 gene may result in Stickler syndrome type 2, which can be differentiated clinically by a ‘beaded’ vitreous and a more severe hearing loss compared to the more prevalent type 1, caused by mutations in COL2A1. In literature, only a few dozen COL11A1 mutations have been reported. We selected 33 unrelated COL2A1 mutation-negative patients, based on their clinical features, for molecular COL11A1 analysis, by means of next-generation sequencing technology (MiSeq, Illumina). The bioinformatic pipeline included the CLC bio Workbench 6.0 followed by an in-house developed software package for variant interpretation. Assays lacking sufficient coverage as well as the mutations ...

Research paper thumbnail of Motor performance and vestibular function in children diagnosed with congenital cytomegalovirus (cCMV) infection or connexin 26 (Cx26) mutation

Research paper thumbnail of Effect of MRI on distortion product otoacoustic emissions in neonates : a pilot study

Research paper thumbnail of Hearing impairment in children with Stickler syndrome: review of phenotype and correlation with genotype

Research paper thumbnail of Cranial ultrasound and MRI: complementary or not in the diagnostic assessment of children with congenital CMV infection?

European Journal of Pediatrics

Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both ... more Whether or not cranial ultrasound (crUS) and cerebral magnetic resonance imaging (MRI) have both a place in the assessment of children with congenital cytomegalovirus infection (cCMV) remains a topic of discussion between research groups. Literature suggests that MRI is indicated only in children with abnormal crUS. In Flanders, Belgium, combined crUS and MRI was performed on 639 children with cCMV, referred for diagnostic assessment. Cranial US was classified as abnormal in the presence of striatal vasculopathy, calcifications, cysts, cystic germinolysis, and/or ventriculomegaly. MRI findings were classified as abnormal in the presence of gyration disorders, cerebellar abnormalities, ventriculomegaly, cysts, or pathologic white matter lesions. One in five children (93/480) with normal crUS showed abnormal findings on MRI. Of them, 85 (91.4%) were classified as symptomatic. In 37 of those 93 children (39.8%), classification as severely symptomatic was made based on MRI lesions alone. MRI and crUS proved to be complementary in the assessment of CNS involvement in children with cCMV. Long-term studies are needed to evaluate the importance of this finding with respect to outcome and benefit of therapy in this particular subgroup of patients with cCMV infection. Conclusion: Our findings support an enhanced role of MRI in the diagnosis of CNS involvement in children with cCMV infection. The ideal assessment should include both imaging techniques, as the strengths of each test compensate for the other’s weaknesses. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV. What is Known: • Congenital CMV infection involves the central nervous system with direct injury to and possible disruption of brain development. • Experts suggest that MRI is indicated only in children with abnormal crUS. What is New: • In almost 20% of our children with a normal cranial ultrasound, abnormalities were detected on MRI. • Our results suggest that performing both MRI and cranial US is important to obtain a complete assessment of central nervous system involvement in children with cCMV.