The aim of our neurological research in children is to improve our understanding of
1) how the developing nervous system is influenced by genetic and external factors
2) how we can prevent diseases such as cerebral palsy, epilepsy and developmental disorders
3) how we develop new therapeutic approaches to these diseases
The developing brain requires a high energy supply; thus, congenital heart disease may affect brain development in utero. Some congenital heart diseases are caused by genetics, such as 22q11 deletion syndrome and Down’s syndrome. By comparing brain development in children with congenital heart disease with and without a genetic background, we can study the impact of genetic changes and mechanical intrauterine circulation problems, respectively on cerebral developmental problems in children with congenital malformations of the heart.
We conduct a registry-based study identifying the risk of cerebral palsy, epilepsy and behavioural disabilities in children experiencing respiratory distress syndrome during the neonatal period.
An epidemiological study of children with cerebral palsy investigates the impact of children’s cognitive function and parental level of education on choice of treatment modality and presence of psychiatric manifestations.
The Centre for Rare Diseases is one of two centres in Denmark treating children with rare genetic diseases. Most of the patients with very rare syndromes have accompanying mental, motorskill, behavioural and seizure-related problems due to an accompanying developmental disorder of the brain. By examining the occurrence of specific epilepsy types, specific learning difficulties, and general problems like insomnia and language disorders in children with rare syndromes, we can obtain new knowledge of the aetiology of major neurological and psychiatric diseases. We have ongoing projects describing the incidence of autism, epilepsy and learning disabilities in patients with Angelman syndrome, where genetic imprinting has a certain impact on brain development. Another example is a project carried out in collaboration with Sct. Hans’s Psychiatric Hospital in Copenhagen, where we examine the prevalence of predictors in childhood for the development of schizophrenia in 22q11 deletion syndrome in adolescents. We have just completed a project demonstrating an increased incidence of loneliness in children and adolescents with Neurofibromatosis Recklinghausen type 1 (NF-1) and found a correlation to depression and perception of own illness. A large clinical study starting in 2015 will investigate the genotype-phenotype relationship in patients with NF-1.
Møbius syndrome is caused by a congenital lack of two to five cranial nerves, including as a miniumum, N. facialis and N. abducens. Children with Møbius syndrome thus lack the ability to smile and demonstrate anger by use of facial features. How this affects the socio-psychiatric development of these children is investigated in a large international study.
Many of the rare syndromes cause mental, motor skill, behavioural and growth problems, most often due to genetic imprintning, and through clinical research on epigenetic sister diseases such as Beckwith-Wiedeman /Silver Russel syndrome and Angelman/Prader-Willi syndrome we will generate new knowledge about children's normal and abnormal growth. We have demonstrated that children with Angelman syndrome have eating behaviour and obesity patterns similar to that seen with Prader-Willi syndrome due to pUPD of chromosome 15. A study of the neuro-endocrine features of Angelman syndrome is thus planned.
In cooperation with a genetic laboratory in Houston, Texas we have described a new genetic disease (Multisystemic Smooth Muscle Dysfunction Syndrome; #OMIM 613834) which is caused by a de novo mutation in ACTA2 (R179H) and accompanied by smooth muscle dysfunction in all organs with smooth muscle cells such as? blood vessels, lungs, and intestines. The disease is characterised by disturbed development of large and small vessels in the brain, dilatation of the ascending aorta, hypotonic bladder function (urine and bile), intestinal motility disorders, changes in lung function and ocular neo-vascularisation. A mouse model of the disease is currently developed and if successful ,we will perform in vivo and in vitro studies on vessels, lung, uterus and bladder tissue to obtain new knowledge on diseases where smooth muscle cells are involved and to get new angles to treatment?.
Autism and Angelman syndrome
Trillingsgaard A & Ostergaard JR, Autism 8: 163-174, 2004
Mortality in children with febrile seizure
Vestergaard M et al, Lancet 372: 457-463, 2008
De novo mutation ACTA2 Causes a Novel Syndrome of global smooth muscle dysfunction
Milevicz DM et al, Am J Med Genet 152A: 2437-2443, 2010
Cardiac involvement meant in Batten disease
Ostergaard JR et al, Neurology 76, 1245-1251, 2011
Important international partners
Dianna M. Milewicz, M.D., PhD
UT Medical School, Department of Medical Genetics
6431 Fannin, MSB 6.100
Houston, Texas 77030, USA
Dr Vijeya Ganesan, M.D., DMSci
Neurosciences Unit, Institute of Child Health
The Wolfson Centre, Mecklenburgh Square
London WC1N 2AP, England
Jonathan W. Mink, M.D., PhD
University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 631
Rochester, NY 14642, USA