Most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome 1. Turner syndrome is caused by complete or partial absence of the second sex chromosome in girls. We describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome diagnosed at birth and Turner syndrome at 14 years 9 months. Short stature was initially misattributed to Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome. We discuss the prevalence of delayed diagnosis of Turner syndrome, the rarity of reports of concurrent autosomal chromosome mutation and sex chromosome deletion, as well as the need to consider the diagnosis of Turner syndrome in all girls with short stature regardless of prior medical history.

Rett syndrome is the manifestation of an X linked, mainly female, genetic, neurodevelopmental disorder that usually produces profound intellectual and physical disabilities including abnormal muscle tone, with a tendency to develop limb contractures, scoliosis, epilepsy and irregular respiration. There is characteristic hand stereotypy with· poor voluntary hand use, locomotion is compromised and speech is rare. Although the disorder is not progressive many sequele shorten life especially in the most severely affected. Subtle abnormalities, present from birth, are frequently overlooked because there is some developmental progress until a period of regression at around one year of age when speech and hand use diminish. This thesis gives an account of clinical, physiological and genetic studies carried out between 1982 and 2005 with the aim of recording the natural history of the disorder and understanding its clinical manifestations. The subjects of these studies have been people of all ages, mainly from the British Isles, reported to have Rett syndrome by their physicians and families or carers (British Isles Survey, n=l228). Most have been examined and recorded on video by myself, many repeatedly. Fully informed parental consent and appropriate ethical approval has been given for all procedures. The early manifestations of the disorder were investigated from developmental histories and donated videos (78) taken by families before they were aware of the problem. The abnormal respiratory rhythms were investigated and characterised, using non-invasive measures of respiratory rhythm, carbon dioxide, oxygen, heart rate and blood pressure. The poor control of voluntary movement was investigated using electromagnetic stimulation of the cortex to record conduction in the motor pathways. Stereotyped hand movements were analysed from three-dimensional live recording and informal two-dimensional video. The prevalence of a toe anomaly was estimated, visual evoked potentials were recorded and a reported increase in urinary neopterin was investigated. The health of people in the British Survey was monitored longitudinally from family and physician reports and direct clinical examinations, data being stored on computer. Simple scores were generated to indicate separately the severity of the condition and health of the individual. The survey data has been used to estimate the prevalence of the disorder (I in 10,000 females), natural history from birth to death, the predictive value of the earliest signs, survival at different levels of severity, the impact of scoliosis surgery on health and has provided a foundation for studies relating clinical manifestations to specific mutations on the affected gene MECP 2 (Xq28). The studies have indicated the nature of the Rett disorder to be developmental and non-progressive, with primary impact on the processing functions of the brain, probably beginning in the brain stem before birth.

Since the 17th century there has been a certain confusion in diagnosis of what is now called the Ehlers-Danlos syndrome. In 1682 Meekrin described the case of a Spaniard who could make his skin stretch to an enormous extent, and appears to have confused the Ehlers-Danlos syndrome with the condition of cutis laxa. No further significant literature appeared until Unna (1896) described the histology of elastic skin, but the syndrome as such had not then been recognised. In 1900 Ehlers presented a case at the Danish Society of Dermatology which he described as "Cutis laxa, with a tendency to haemorrhage in the skin and to laxity of the joints", and in the same year Sir Malcolm Morris demonstrated a case at the British Dermatological Society which he called "Loose skin with numerous cutaneous nodules". This was followed in 1906 by a case shown by Hallopeau and Lepinay which they called "Diabetic Xanthorum" but which was probably a case of the Ehlers-Danlos syndrome, as was the case described by Cohn (1907) in Germany. The case of Hallopeau and Lepinay was further reviewed in 1908 by Danlos in France, who described it as "Cutis Laxa with Tumours 'par contusion chronique des coudes et des genoux'". The same case was investigated in the same year by Pautrier who was the first to describe the histology of the condition.

No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / Medicine / Master / Master of Philosophy

Metabolic syndrome includes several metabolic and hormonal disorders, such as abdominal obesity, insulin resistance, and lower blood ghrelin. Women with breastfeeding history exhibit a reduced risk for metabolic syndrome in later life. The purpose of aim 1 was to determine the incidence of metabolic syndrome in low income, overweight/obese women in early postpartum and to assess its relationship to lactation status. It has been found that the incidence of metabolic syndrome is much higher in formula feeding women than that of the breastfeeding ones (44.3% vs. 22.4%, p < 0.01). The breastfeeding mothers had reduced triglycerides (109.07 mg/dl vs. 143.10 mg/dl, p < 001) and elevated serum high-density lipoprotein (HDL)-cholesterol (58.59 mg/dl vs. 51.76 mg/dl, p < 0.01). The goal of aim 2 was to explore associations between ghrelin, metabolic syndrome and infant feeding methods in low income, overweight/obese women in early postpartum. In our study, the breastfeeding mothers in early postpartum had higher plasma ghrelin, as compared to those who formula fed (584.73 pg/ml vs. 450.77 pg/ml, p < 0.01). Additionally, it is found that plasma ghrelin was negatively associated with incidence and numbers of risk factors for metabolic syndrome, before and after controlling for body mass index (BMI). After adjusting for ghrelin in logistic regression analyses, significant relationships between lactation status and metabolic syndrome disappeared. Thus, the protective function of breastfeeding against metabolic syndrome in overweight/obese women in early postpartum may related to the plasma ghrelin values. The purpose of aim 3 was to detect the influence of weight loss on insulin resistance and plasma adiponectin, zinc (Zn), manganese (Mn) and copper (Cu) in low income, overweight/obese women in early postpartum. After an eight-week weight loss intervention, plasma levels of adiponectin, Zn and Mn were significantly enhanced, and plasma concentrations of insulin (7.53±0.56 vs. 6.23±0.49, p <0.01) and insulin resistance (1.84±0.15 vs. 1.44±0.12, p <0.01) were reduced. The increase of adiponectin, Zn and Mn was positively associated with weight reduction. However, the plasma Cu was not significantly affected. The relationships between weight loss and reduced insulin resistance disappeared after adjusting the increases of adiponectin, Zn and Mn during weight loss. Thus, weight loss had beneficial effects on insulin resistance, plasma values of adiponectin Zn and Mn. It is plausible that the influence of weight loss on insulin resistance may be associated with improvements of plasma of adiponectin, Zn and Mn. Collectively, the results of this study demonstrate the important benefits of breastfeeding on prevention of metabolic syndrome in overweight/obese women in early postpartum. This study also emphasizes the influence of ghrelin on risk factors of metabolic syndrome and lactation status. / text

Children with Down syndrome present with an array of physical and cognitive sequelae that can hinder speech and language development. These individuals can constitute a considerable portion of a speech-language pathologist’s caseload. Based on the principles of best evidence, clinicians are ethically responsible for providing the most effective treatment for their clients. The available literature focuses mainly on describing the linguistic characteristics in this population, while relatively less focus is placed on effective intervention programs. This paper investigates the available evidence regarding speech and language interventions for children with Down syndrome who are in the mild to moderate range of linguistic functioning, and provides an outlook for future research based on best evidence. / text

An exploratory pilot study was conducted to identify specific experiences, perceptions and challenges of participants affected by Turner Syndrome in Hong Kong. It was important to discover how issues concerning fertility, menstruation, ovarian function and ovarian insufficiency and hormone replacement therapy, which are important to these women have impacted their psychosocial wellbeing, psychosocial experiences and their relationships. An ‘across the life span’ approach was used to explore significant issues at various stages or ‘moments’ of their lives, and which they perceive to be important to family and the Chinese culture. The findings of this study has implications for the role of genetic counselling in Turner Syndrome in Hong Kong, to facilitate individuals and their families to meet the challenge. When parents make prenatal decisions for the continuation of pregnancy of a fetus with Turner Syndrome, the quality of genetic counselling is considered to have direct effect on the decision making and continuance of pregnancy. Previous literature indicated that critical criteria for decision making during the prenatal period includes the potential future fertility of the fetus. These issues concerning fertility of patients with Turner Syndrome were explored in this study, in addition to a review of the existing literature. Methodology This was a study of qualitative research, using semi structured interviews. Triangulation techniques were employed in order to gain a rich insight into the care of patients with Turner Syndrome in Hong Kong. For this report, four participants were recruited, who were existing patients of the Department of Reproductive Medicine clinic in Queen Mary Hospital. Each consented to an in depth interview concerning their experiences and challenges of Turner Syndrome in Hong Kong. The narrative of the interview was analysed according to the themes which emerged. A review of medical notes of the participants from the Department of Reproductive Medicine clinic in Queen Mary Hospital, Hong Kong was also conducted. Results Of the participants included in this analysis, one individual with classical features of Turner Syndrome had a 45, X karyotype. The remaining three participants were cytogenetically diagnosed with a mosaicism for Turner Syndrome. It was anticipated that the knowledge gained would improve the provision of information and care by the genetic counsellor and medical practitioner, for patients or parents at initial diagnosis and across their lifespan. The study participants were able to provide rich body of data allowing insight into their lives, experiences and challenges. The pregnancy losses that they have endured, and the hope that all four individuals sustain became evident with each interaction. Significance This study has shown that patients require an in depth knowledge of their condition. They trust the medical professionals who care for them, and their care should be managed with continuity ‘across the life span’ by carers who are experts in Turner Syndrome. Their need for establishment of support groups, and a continuing support structure is essential to their well-being and their psychological health. This is a unique study in Hong Kong with these issues having not been explored previously. / published_or_final_version / Medicine / Master / Master of Medical Sciences

No description available.