PubMed Health⌕ Search

Biomedical subjects

H Leonard

Publications and source records attributed to H Leonard.

At least 19 recordsLinked to original sources
PubMed2003

Pediatric cardiac transplant: results using a steroid-free maintenance regimen.

We report on survival, rejection, lymphoma and renal function following cardiac transplant using a steroid-free maintenance immunosuppressive regimen. We have performed 73 cardiac transplants in 71 children under 16 yr of age in the last 12 yr. There were eight perioperative and four late deaths giving actuarial survival of 88, 88, 85 and 70% at 1, 2, 5 and 10 yr, respectively. A total of 11 (15.3%) children had one episode of rejection (grade 3) in the first 6 months; one died and one was re-transplanted because of rejection. There was only one episode of late rejection (8 yr post-transplant) because of low drug levels in a patient with lymphoma and sepsis. This patient did not survive. Three other children (5.6%) also developed lymphoma and recovered but one died subsequently of graft failure. Four children have developed severe renal failure (glomerular filtration rate GFR <30 mL/min/m2). Two have not survived and one is expected to commence dialysis soon. The remainder have mild to moderate renal impairment. We report excellent survival and low rejection rates without use of long-term steroids. However the doses of cyclosporin used have had a significant effect on renal function in many cases.

Adolescent↗
PubMed2003

Describing the phenotype in Rett syndrome using a population database.

BACKGROUND: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes. AIMS: To describe the variation in phenotype in Rett syndrome using four different scales, by means of a population database. METHODS: Using multiple sources of ascertainment including the Australian Paediatric Surveillance Unit, the development of an Australian cohort of Rett syndrome cases born since 1976 has provided the first genetically characterised population based study of Rett syndrome. Follow up questionnaires were administered in 2000 to families and used to provide responses for items in four different severity scales. RESULTS: A total of 199 verified cases of Rett syndrome were reported between January 1993 and July 2000; 152 families provided information for the follow up study. The mean score using the Kerr scale was 22.9 (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17 years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and ranged from 18 to 75. CONCLUSION: We have expanded on the descriptive epidemiology of Rett syndrome and shown different patterns according to the severity scale selected. Although all affected children are severely functionally dependent, it is still possible to identify some variation in ability, even in children with identified MECP2 mutations.

Adolescent↗
PubMed2002

Functional status of school-aged children with Down syndrome.

OBJECTIVE: To field test, in questionnaire format, the Functional Independence Measure for Children (WeeFIM, a schedule usually administered by interview) on parents of a cohort of school-aged children with Down syndrome. METHODS: The parents of 211 Western Australian children with Down syndrome participated in the present study, representing 79.9% of all children with Down syndrome in the State. Subjects were identified using two sources: (i) the Birth Defects Registry; and (ii) the Disability Services Commission. RESULTS: The total WeeFIM score was 106.2 +/- 17.0 (mean +/- SD) out of a possible 126. Girls scored higher than boys (108.6 vs 103.6; P = 0.05). Scores increased across all age groups (P < 0.0001), even relative to normative data. Performance was strongest in the transfer and locomotion domains and weakest in social cognition. CONCLUSION: We found that severe functional limitations are rare in school-aged children with Down syndrome. Some support and supervision are required for complex self-care, communication and social skill tasks. This study demonstrates the feasibility of using the WeeFIM for collecting population survey data in children with developmental disability. This may be useful for the longitudinal tracking of such populations, as well as the monitoring of response to interventions.

Activities of Daily Living↗
PubMed2001

Guidelines for reporting clinical features in cases with MECP2 mutations.

An international group recommends that papers relating phenotypes to genotypes involving mutations in the X chromosome gene MECP2 should provide a minimum data set reporting the range of disturbances frequently encountered in Rett Syndrome. A simple scoring system is suggested which will facilitate comparison among the various clinical profiles. Features are described which should prompt screening for MECP2 mutations.

Chromosomal Proteins, Non-Histone↗
PubMed2001

Medium-term open label trial of L-carnitine in Rett syndrome.

Treatment strategies in Rett syndrome so far have been essentially symptomatic and supportive. In order to establish the medium-term effects of L-carnitine, an open label trial was performed in a cohort of 21 Rett syndrome females, with a control group of 62 Rett syndrome females of a similar age, for a 6-month period. Compared with the Rett syndrome controls, treatment with L-carnitine led to significant improvements in sleep efficiency (P=0.027), especially in the subjects with a baseline sleep efficiency less than 90%, energy level (P<0.005) and communication skills (P=0.004). There was no significant difference in the subject's level of physical activity, hand function or in the quality of life of the subject's parents. In addition, before and after comparisons of the treatment group showed improvements in expressive speech (P=0.011). Treatment with L-carnitine seems to be of significant benefit in a subgroup of girls with Rett syndrome. In these girls, small but discernible improvements may be of considerable importance to their parents and carers.

Adolescent↗
PubMed2001

Sleep dysfunction in Rett syndrome: lack of age related decrease in sleep duration.

The sleep patterns of a cohort of 83 Rett syndrome females were characterized using a sleep diary for 7 consecutive days and nights and compared with normative sleep data. The mean total sleep time of the cohort was 10.75 h, daytime sleep 0.77 h, sleep efficiency 89.7%, and sleep latency 0.52 h. When subjects were categorized according to age and Rett syndrome classification, there was no significant difference in their sleep characteristics. There was a significant difference in the percentage predicted total sleep time (P<0.001) and Z scores for total sleep time (P<0.001), when subjects were categorized according to age and compared with normal children. The Rett syndrome subjects in this study did not show the age related decrease in total and daytime sleep time seen in normal children. The immature sleep pattern demonstrated in this cohort, may be a consequence of arrested brain development.

Adolescent↗
PubMed2001

Using the Internet to pilot a questionnaire on childhood disability in Rett syndrome.

There is increasing use of the Internet for the transfer and sharing of medical information. Opportunities to pilot surveys online are now also available. An online HTML questionnaire allowed us to pilot a questionnaire about functional ability and the use of health services in Rett syndrome, a rare neurological disorder. Subscribers to a list server completed the online questionnaire and returned data by CGI script-formatted e-mail. Text boxes were provided for open-ended questions. Eighty-six questionnaires were returned from 224 subscribers with 76% returned within the first week. Almost all respondents were Caucasian, well educated and English speaking. The issue of selection bias and the need for mechanisms to validate the diagnosis are important considerations in any research facilitated through the Internet. However, we were able to contact an otherwise inaccessible group in a fast and cost-efficient manner and effectively pilot our survey without tapping into our own study population.

Adolescent↗
PubMed2001

A case of multiple congenital anomalies in association with Rett syndrome confirmed by MECP2 mutation screening.

Rett syndrome (RTT) is a severe neurodevelopmental disorder. Apparently normal at birth, girls with RTT undergo developmental regression and acquire a neurological and behavioural phenotype that has been used to define clinical diagnostic criteria for the disorder. Recently mutations in the methyl-CpG binding protein 2 gene (MECP2), located on Xq28 have been identified in females with RTT. We report a girl whose clinical course was complicated by congenital abnormalities of the respiratory tract and gastrointestinal system. In addition neurological abnormalities were evident in the newborn period. By the age of 3 years she had developed a phenotype very suggestive of RTT, but had not demonstrated deceleration of head growth and the development of expressive language was prevented by the presence of the tracheostomy. The clinical impression of RTT was confirmed by the recent finding of a mutation in the MECP2 gene. This case report highlights the importance of considering the clinical diagnosis of RTT even in the presence of other conditions and emphasises that girls with RTT may not be normal from birth.

Abnormalities, Multiple↗
PubMed2001

Friedreich's ataxia presenting after cardiac transplantation.

A 4 year old boy underwent cardiac transplantation because of cardiomyopathy with ischaemia. Following transplantation he developed neurological signs of Friedreich's ataxia and the diagnosis was confirmed with genetic testing. Cardiomyopathy is a rare presentation of Friedreich's ataxia and to our knowledge this is the first reported transplant operation for the cardiomyopathy associated with this condition.

Age of Onset↗
PubMed2001

The influence of congenital heart disease on survival of infants with oesophageal atresia.

OBJECTIVE: To examine the prevalence of congenital heart disease in babies with oesophageal atresia and its influence on outcome. DESIGN: Retrospective analysis. SETTING: The resident population of one health region. RESULTS: A total of 153 babies with oesophageal atresia were identified from 509 975 live births (0.30 per 1000); 26 (17%) had cardiac defects. Survival of babies with normal hearts was 97%, 97%, and 95% at one week, one month, and one year. Survival of babies with congenital heart disease was 85%, 85%, and 67% at one week, one month, and one year, but only one of ten deaths was the result of the congenital heart disease. The remaining deaths were due to other congenital malformations, respiratory disease, or chromosome abnormalities. CONCLUSIONS: There is a high prevalence of congenital heart disease in babies with oesophageal atresia. Congenital heart disease is associated with a higher mortality in oesophageal atresia but it is not the cause of it.

Cause of Death↗
PubMed2001

Occurrence of Rett syndrome in boys.

The neurologic disorder Rett syndrome was originally described exclusively in girls. We present two boys with clinical features of Rett syndrome. Other than head circumference deceleration, no longer considered mandatory, patient 1 meets all of the criteria. Using fluorescent in situ hybridization analysis, 97.6% of cells were found to be karyotypically normal (46,XY). No mutation was detected on screening of the coding region of the MECP2 gene. The second patient also has classic features of Rett syndrome. However, cytogenetic analysis of peripheral blood revealed a karyotype 47,XXY[23]/46,XY[7] confirming mosaicism for Klinefelter's syndrome. A T158M missense mutation in the methylcytosine-binding domain of the MECP2 gene was identified. A diagnostic bias against the clinical identification of Rett syndrome in boys may exist. This presentation of the male phenotype could be more common than it would appear, although boys with MECP2 mutations might also manifest in other ways. Rett syndrome remains a clinical diagnosis that should not be dismissed in boys, and thorough evaluation including karyotype and mutation testing is warranted.

Brain↗
PubMed2000

Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: correlation of disease severity with mutation type and location.

Mutations in the methyl-CpG-binding protein gene MECP2 at Xq28 cause Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by a period of stagnation followed by regression in the development of young girls. Mutations were sought in MECP2 in 48 females with classical sporadic RTT, seven families with possible familial RTT and five sporadic females with features suggestive, but not diagnostic of RTT. Long distance PCR coupled with long-read direct sequencing was employed to sequence the entire MECP2 gene coding region in all cases. Mutations were identified in 44/55 (80%) unrelated classical sporadic and familial RTT patients, but only 1/5 (20%) sporadic cases with suggestive but non-diagnostic features of RTT. Twenty-one different mutations were identified (12 missense, four nonsense and five frame-shift mutations); 14 of these were novel. All missense mutations were located either in the methyl-CpG-binding domain or in the transcription repression domain. Nine recurrent mutations were characterized in a total of 33 unrelated cases (73% of all cases with MECP2 mutations). Significantly milder disease was noted in patients carrying missense mutations as compared with those with truncating mutations ( P = 0. 0023), and milder disease was associated with late as compared with early truncating mutations ( P = 0.0190).

Amino Acid Sequence↗
PubMed2000

Using genetic epidemiology to study Rett syndrome: the design of a case-control study.

Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underlying mechanism remains obscure. One favoured hypothesis is that the syndrome is an X-linked dominant disorder, lethal or non-expressed in males. Genealogical research has also suggested that the mode of transmission in Rett syndrome may involve a premutation which over several generations is converted to a full mutation. Geographical clustering has been reported, and it has also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in families with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls with Rett syndrome. The science of genetic epidemiology can be used to identify familial aggregation, which is the clustering of a disorder within a family. We have used a case-control study design to investigate both fetal wastage and familial aggregation of other disorders in families of girls with Rett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal development. This paper describes the methodology for a case-control study of this rare condition using pedigree data and discusses issues in the collection and evaluation of such data. The use of a control population is an important feature. Both the strengths and the shortcomings of our design are identified, and recommendations are made for future research.

Australia↗
PubMed2000

Survival of infants born with Down's syndrome: 1980-96.

The improved life expectancy of people with Down's syndrome as a result of the greater availability of surgery and advances in medical care has been widely documented. However, there has been no evaluation of survival in the Australian Down's syndrome population since the 1980s. This study aimed to evaluate the changes in survival from birth in cases of Down's syndrome notified to the Birth Defects Registry in Western Australia. Babies born with Down's syndrome between 1980 and 1996 (inclusive) and registered with the Birth Defects Registry were studied. Survival status was obtained in several ways. Cases were stratified into three cohorts for comparison. Survival curves were constructed using the methods of Kaplan and Meier. For infants born during 1980-96, survival to 1 year is now > 91%, and 85% can expect to survive until the age of 10 years. Although survival in those with heart disease showed improvement over the period studied, overall this was still a strong predictor of mortality. Survival in Aboriginal children with Down's syndrome was significantly poorer than in non-Aboriginal children, mirroring the pattern in the general population. Mortality was greater in females and in those with a low birthweight. There was no statistically significant difference in the survival between those born in metropolitan and in rural areas. There has been a considerable improvement in survival of infants born with Down's syndrome in Western Australia. This improvement is similar to findings in recent international studies. The difference in survival between Aboriginal and non-Aboriginal children is particularly disturbing. These findings are useful for both clinicians and families who need to plan for the long-term care of these children.

Adult↗
PubMed2000

Intellectual disability in Western Australia.

OBJECTIVE: To investigate the prevalence of intellectual disability in Western Australia (WA), its causes, prevention, and trends over time. METHODOLOGY: Data from an administrative database of intellectual disability in WA were used to report on the trends in intellectual disability in childhood. RESULTS: The prevalence of intellectual disability was 8.3 per 1000 live births in 1980-90. For half the cases, there was no known cause for the intellectual disability. Down syndrome accounted for 14 to 15% of all cases. Since the introduction of newborn screening, no WA-born child participating in the screening program has been diagnosed with intellectual disability as a result of either phenylketonuria or congenital hypothyroidism. The rate of autism spectrum disorders rose from three to six per 10 000 in the 1980-83 WA birth cohort to 10-13 per 10 000 for the 1989-92 cohort. CONCLUSIONS: Recent linkage of this administrative database to the WA Maternal and Child Health Research Data Base provides a unique opportunity for more detailed investigation of intellectual disability and its risk factors in a large, well-ascertained population of children.

Autistic Disorder↗