Monday 30 November 2009
Friday 20 November 2009
Tourette, Discussion
Neuroligins are an intriguing study target for neuropsychiatric conditions due to their potential role in synapse function and neuron-to-neuron recognition.
Lack of expression of specific neuroligins could affect neuronal interactions within the synaptic network, leading to consequent neuropathology
This family's varied neuropsychiatric phenotypes suggest that mutations in NLGN4 may be associated with a wider clinical spectrum than previously described, including depression, anxiety, and tic disorders.
Their varied pheno-types, all associated with the same mutation, suggest that epigenetic factors play a role in determining presentation.
This also suggests that derangement of core elements of synapse function may be associated with multiple neuropsychiatric conditions.
Gene dosage may be integral to neuroligin function as suggested by the mother's relatively mild symptoms (as compared wth her sons) of learning disorder, anxiety, and depression.
Knowledge of the mother's X-chromosome inactivation status would be valuable in this interpretation, but was unfortunately not available.
This may have important genetic counseling implications, as carrier mothers with mild symptoms may be at risk to have severely affected offspring.
Lack of expression of specific neuroligins could affect neuronal interactions within the synaptic network, leading to consequent neuropathology
This family's varied neuropsychiatric phenotypes suggest that mutations in NLGN4 may be associated with a wider clinical spectrum than previously described, including depression, anxiety, and tic disorders.
Their varied pheno-types, all associated with the same mutation, suggest that epigenetic factors play a role in determining presentation.
This also suggests that derangement of core elements of synapse function may be associated with multiple neuropsychiatric conditions.
Gene dosage may be integral to neuroligin function as suggested by the mother's relatively mild symptoms (as compared wth her sons) of learning disorder, anxiety, and depression.
Knowledge of the mother's X-chromosome inactivation status would be valuable in this interpretation, but was unfortunately not available.
This may have important genetic counseling implications, as carrier mothers with mild symptoms may be at risk to have severely affected offspring.
familial deletion within NLGN4 associated with autism and tourette
Neuroligin 4 (NLGN4) is a member of a cell adhesion protein family that apperars to play a role in the maturation and function of neuronal synapses.
Mutations in the x-linked NLGN4 gene are a potential cause of autistic spectrum disorders, and mutations have been reported in several patients with autism, Asperger syndrome, and mental retardation.
We describe here a family with a wide variation in neuropsychiatric illness associated with a deletion of exons 4,5, and 6 of the NLGN4.
The proband is an autistic boy with a motor tic. his brother has Tourette syndrome and attention deficit hyperactivity disorder.
Their mother, a carrier, has a learning disorder, anxiety, and depression.
This family demonstrates that NLGN4 mutations can be associated with a wide spectrum of neuropsychiatric conditions and that carriers may be affected with milder symptoms.
(This is not my family it was another study done in the USA)
but this does relate to my family, ie i have a brother with (XLI) autism and (ADHD) and Tourette syndrome.
And my son Chris and Stephen have a tick disorder wich means they could also have Tourette's, but this has not been diagnosed as yet.
Mutations in the x-linked NLGN4 gene are a potential cause of autistic spectrum disorders, and mutations have been reported in several patients with autism, Asperger syndrome, and mental retardation.
We describe here a family with a wide variation in neuropsychiatric illness associated with a deletion of exons 4,5, and 6 of the NLGN4.
The proband is an autistic boy with a motor tic. his brother has Tourette syndrome and attention deficit hyperactivity disorder.
Their mother, a carrier, has a learning disorder, anxiety, and depression.
This family demonstrates that NLGN4 mutations can be associated with a wide spectrum of neuropsychiatric conditions and that carriers may be affected with milder symptoms.
(This is not my family it was another study done in the USA)
but this does relate to my family, ie i have a brother with (XLI) autism and (ADHD) and Tourette syndrome.
And my son Chris and Stephen have a tick disorder wich means they could also have Tourette's, but this has not been diagnosed as yet.
Tuesday 10 November 2009
Discussion
This study is the first to address systematically the cognitive behavioural phenotype of boys with X-linked ichthyosis,and provides evidence for an increased risk of inattentive ADHD subtype diagnosis and autistic spectrum difficulties.
Within the general population, rates of ADHD in boys in the UK are reported as 3.6%(1% have the in attentive subtype, 0.28% the hyperactive subtype and 2.34% the combined subtype).
In this study, 40% fulfil DSM-IV criteria for ADHD; even after removing the two children with an ASD, a 32% diagnostic rate is still considerably higher than the general population.
A major strength of the study was the ascertainment of families through the maternal serum screening programme, in orderto avoid bias, suggesting that these results are generalisableto boys with XLI in general.
Intriguingly, of the 32% with an ADHD diagnosis, all of these children fulfilled criteria for inattentive subtype only, and there was no correlation with the underlying molecular pathology of the STS gene.
Both deletions and presumed point mutations were associated with these symptoms, suggesting that it may be STS deficiency per se that is causing the increased risk if inattentive symptoms in these boys, rather than the presence of the deletion.
There are several lines of evidence in the literature to support this hypothesis.
Of particular interest is a recent finding from animal studies suggesting that haploinsufficiency of the STS gene may account for the attentional deficits seen in 39XO mice.
STS converts the sulfated from of dehydroepiandrosterone, know as DHEA-S, to DHEA.
Both are neurosteroids with effects on neurophysiological and bshavioural processes, including some evidence for an inverse relationship between DHEA blood values and clinical symptomatology in boys with ADHD.
Additionally, a 3 month treatment course of methylphenidate, the most common treatment for ADHD, produced significant clinical improvement in the boys with ADHD and increases in serum concentrations of DHEAS and DHEA, suggesting that these neurosteroids may play a role in the therapeutic effects of methylphenidate.
DHEA administration to patients with schizophrenia, alongside their usual antipsychotic medication, has also been shown to improve visual sustained attention.
We have identified three unrelated families with boys with XLI and large deletions associated in all cases with either autism or language/communication problems.
It is possible that in all three families deletion of the NLGN4 gene accounts for the autistic difficulties, as several cases of autistic spectrum disorders associated with mutations within this gene have been previously reported.
One of the boys originally described by jamain et al, in addition to the diagnosis of Asperger's syndrome, also had communication difficulties described as "dysarthria" which may be relevant to one of the boys described here with severe verbal dyspraxia.
Within the general population, rates of ADHD in boys in the UK are reported as 3.6%(1% have the in attentive subtype, 0.28% the hyperactive subtype and 2.34% the combined subtype).
In this study, 40% fulfil DSM-IV criteria for ADHD; even after removing the two children with an ASD, a 32% diagnostic rate is still considerably higher than the general population.
A major strength of the study was the ascertainment of families through the maternal serum screening programme, in orderto avoid bias, suggesting that these results are generalisableto boys with XLI in general.
Intriguingly, of the 32% with an ADHD diagnosis, all of these children fulfilled criteria for inattentive subtype only, and there was no correlation with the underlying molecular pathology of the STS gene.
Both deletions and presumed point mutations were associated with these symptoms, suggesting that it may be STS deficiency per se that is causing the increased risk if inattentive symptoms in these boys, rather than the presence of the deletion.
There are several lines of evidence in the literature to support this hypothesis.
Of particular interest is a recent finding from animal studies suggesting that haploinsufficiency of the STS gene may account for the attentional deficits seen in 39XO mice.
STS converts the sulfated from of dehydroepiandrosterone, know as DHEA-S, to DHEA.
Both are neurosteroids with effects on neurophysiological and bshavioural processes, including some evidence for an inverse relationship between DHEA blood values and clinical symptomatology in boys with ADHD.
Additionally, a 3 month treatment course of methylphenidate, the most common treatment for ADHD, produced significant clinical improvement in the boys with ADHD and increases in serum concentrations of DHEAS and DHEA, suggesting that these neurosteroids may play a role in the therapeutic effects of methylphenidate.
DHEA administration to patients with schizophrenia, alongside their usual antipsychotic medication, has also been shown to improve visual sustained attention.
We have identified three unrelated families with boys with XLI and large deletions associated in all cases with either autism or language/communication problems.
It is possible that in all three families deletion of the NLGN4 gene accounts for the autistic difficulties, as several cases of autistic spectrum disorders associated with mutations within this gene have been previously reported.
One of the boys originally described by jamain et al, in addition to the diagnosis of Asperger's syndrome, also had communication difficulties described as "dysarthria" which may be relevant to one of the boys described here with severe verbal dyspraxia.
Monday 9 November 2009
study
We took part in a study in 2008, run by Addenbrooke's Hospital.
And was run by Prof Yates, Dr Kent and Dr Weisblatt.
Out of 25 familys that took part it was down to 3, and we were one of the 3.
Here is an Abstract from that study.
X-Linked Ichthyosis (XLI) is an inherited disorder affecting 1 in 2000 males and in characterised by scaly skin on the scalp, trunk and limbs usually from birth.
The conditionis due to deficiency of the enzyme steroid sulfatase (STS).
In obstetric practice this disorder is known as placental sulfatase deficiency and can be associated with longer gestation and complications in labour due to poor cervical dilataion.
The majority (approx 90%) of individuals with XLI have a complete deletion of the STS gene at Xp22.32.
This deletion is usually the result of aberrant recombination between homologous sequences in the VCX (variably charged, X chromosome) genes flanking the STS locus.
More extensive STS deletions give rise to contiguous gene deletion syndromes which can include the genes for short stature (SHOX), Kallmann sydrome (KAL), X-linked chondrodysplasis punctata (ARSE), and the X-linked ocular albinism (0A1).
Several case reports of patients with Xp deletions and XLI include cognitive behavioural features such as attention deficit hyperactivity disorder (ADHD), mental retardation and autism.
The VCX3A gene (variably charged, X chromosome, 3A; also known as VCX-A) has been proposed to have a role in the occurrence of mental retardation in some XLI individuals.
The neuroligin 4 (NLGN4) gene, which is included in the deleted region in some XLI patients, may have a role in autism and social communication difficulties since mutations in this gene have associated with autism.
In this study, we therefore sought to systematically examine the frequency of the attention deficit hyperactivity symptoms and disorder (ADHD) and autism in boys with XLI.
And was run by Prof Yates, Dr Kent and Dr Weisblatt.
Out of 25 familys that took part it was down to 3, and we were one of the 3.
Here is an Abstract from that study.
X-Linked Ichthyosis (XLI) is an inherited disorder affecting 1 in 2000 males and in characterised by scaly skin on the scalp, trunk and limbs usually from birth.
The conditionis due to deficiency of the enzyme steroid sulfatase (STS).
In obstetric practice this disorder is known as placental sulfatase deficiency and can be associated with longer gestation and complications in labour due to poor cervical dilataion.
The majority (approx 90%) of individuals with XLI have a complete deletion of the STS gene at Xp22.32.
This deletion is usually the result of aberrant recombination between homologous sequences in the VCX (variably charged, X chromosome) genes flanking the STS locus.
More extensive STS deletions give rise to contiguous gene deletion syndromes which can include the genes for short stature (SHOX), Kallmann sydrome (KAL), X-linked chondrodysplasis punctata (ARSE), and the X-linked ocular albinism (0A1).
Several case reports of patients with Xp deletions and XLI include cognitive behavioural features such as attention deficit hyperactivity disorder (ADHD), mental retardation and autism.
The VCX3A gene (variably charged, X chromosome, 3A; also known as VCX-A) has been proposed to have a role in the occurrence of mental retardation in some XLI individuals.
The neuroligin 4 (NLGN4) gene, which is included in the deleted region in some XLI patients, may have a role in autism and social communication difficulties since mutations in this gene have associated with autism.
In this study, we therefore sought to systematically examine the frequency of the attention deficit hyperactivity symptoms and disorder (ADHD) and autism in boys with XLI.
Sunday 8 November 2009
sorry i sound so down in that last post
The next time i will blog i will go into the in's and out's of Ichthyosis.
Life
I have two boys and a brother with Ichthyosis.
I can cope with the skin and the other problems that go with that, what i am having problems with is coping with the Autism and ADHD, I am finding that very hard to deal with and its very upsetting for them and for me and my partner. I dont know who cope's with it better, but we try to deal with it in our own way's, and i spent long long time greving for the children they should have been, but i love them none the less for it.
And what worries me most is whats going to happen to them when they become adults, and when i cant cope with them any more.
I do worry about some of the thoughts i have had and i tell my self to get a grip all the time.
But that doesnt stop the dark thoughts that i have had.
I can cope with the skin and the other problems that go with that, what i am having problems with is coping with the Autism and ADHD, I am finding that very hard to deal with and its very upsetting for them and for me and my partner. I dont know who cope's with it better, but we try to deal with it in our own way's, and i spent long long time greving for the children they should have been, but i love them none the less for it.
And what worries me most is whats going to happen to them when they become adults, and when i cant cope with them any more.
I do worry about some of the thoughts i have had and i tell my self to get a grip all the time.
But that doesnt stop the dark thoughts that i have had.
Subscribe to:
Posts (Atom)
