ABSTRACT
AIM: Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra-neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss-of-function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1-STN1-TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss-of-function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro-vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. METHODS: We assessed the phenotype to be CP and undertook targeted sequencing. RESULTS: Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss-of-function--c.894dup (p.(Asp299Argfs*58)); and one missense--c.707T>C (p.(Leu236Pro)). CONCLUSION: Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1.
Subject(s)
Ataxia/diagnosis , Ataxia/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/genetics , Calcinosis/diagnosis , Calcinosis/genetics , Central Nervous System Cysts/diagnosis , Central Nervous System Cysts/genetics , Genetic Predisposition to Disease , Heterozygote , Leukoencephalopathies/diagnosis , Leukoencephalopathies/genetics , Muscle Spasticity/diagnosis , Muscle Spasticity/genetics , Mutation , Retinal Diseases/diagnosis , Retinal Diseases/genetics , Seizures/diagnosis , Seizures/genetics , Telomere-Binding Proteins/genetics , Alleles , Child , DNA Mutational Analysis , Genetic Association Studies , Humans , Magnetic Resonance Angiography , Male , Models, Molecular , Neuroimaging , Phenotype , Protein Conformation , Structure-Activity Relationship , Telomere-Binding Proteins/chemistry , Tomography, X-Ray ComputedABSTRACT
With only half of individuals prescribed medication actually taking it, the reasons behind non-compliance warrant a thorough understanding. This paper reviews the factors behind medication non-adherence with a special interest in the link between depression and non-compliance. Whilst this link has been evidenced, we propose that non-compliance could be a presenting sign of underlying depression. Implications of the role of depression as a cause of non-compliance - in particular, why a patient might suddenly stop taking their medication - are discussed; further, early intervention to circumvent a major depressive episode could be implemented if recognition of sudden non-compliance is used by clinicians as a diagnostic tool to alert them to screen the patient for depression.
Subject(s)
Depression , Depressive Disorder, Major , Medication Adherence , Aged , Depression/complications , Depression/drug therapy , Depressive Disorder, Major/complications , Depressive Disorder, Major/drug therapy , Humans , Male , Medication Adherence/psychology , Patient ComplianceABSTRACT
Hope underpins the recovery process of mental illness, as recovery depends on the notion that a patient desires to get better. This makes hope the route by which it occurs. Here, we assess the importance of hope in recovery by exploring what recovery means; the relevance of hope and other factors in achieving it; and finally, the difficulties surrounding maintaining hope. We attempt to discuss hope in the context of recovery from three different situations; Depression, Anorexia Nervosa, and Schizophrenia, and therefore we consider what recovery means in each of these situations and hence the role of hope in each of them. The journey of recovery is an on-going, personal process, which aims to allow a person to have a satisfying life despite the limitations posed by their condition. Several factors are important in permitting it, ranging from learning how to manage one's condition, to improving self- esteem. However, the central tenet in recovery is hope- it is the catalyst for change, and the enabler of the other factors involved in recovery to take charge. Whilst problems exist in helping an individual believe in it, there exist definite routes by which it can be done, such as education and reducing stigma. Ultimately, hope is just as important in recovery from mental illness as in physical illness because hope matters in any situation - the only difference is that in mental illness, the end point is much harder to rationalize in the patient's mind because it requires an awareness that one's mental state is not fixed, the truth being that mental illnesses are not part of one's nature, but are states of mind which can be changed in many instances. Therefore, we must work even harder to ensure this belief is instilled in those suffering from mental illness because hope offers the means by which a better future can be perceived; and therefore, achieved.
