Prader-Willi and Angelman syndromes. Disorders of genomic imprinting

OBJECTIVE: To develop estimates of state Medicaid expenditures attributable to smoking for fiscal year 1993. METHODS: The smoking-attributable fractions (SAFs) of state Medicaid expenditures were estimated using a national model that describes the relationship between smoking and medical expenditures, controlling for a variety of sociodemographic, economic, and behavioral factors. RESULTS: In fiscal year 1993, the SAF for all states (all types of expenditures) was 14.4%, with a range from 8.6% in Washington DC to 19.2% in Nevada. On average, SAFs ranged from a low of 7.9% for home health services expenditures to 21.7% for hospital expenditures. An estimated total of $12.9 billion of fiscal year 1993 Medicaid expenditures was attributable to smoking. The relative error of this estimate was 40.3%. CONCLUSIONS: Cigarette smoking accounts for a substantial portion of annual state Medicaid expenditures, with considerable variation among states. The range in expenditures among the states is due to differences in smoking prevalence, health status, other socioeconomic variables used in the model, and the level and scope of the Medicaid program.     

Diagnostic testing for Prader-Willi and Angelman syndromes: response

Between 1992 and 1997, every year, approximately 30,000 examinations of the liver and bile ducts were done. Addition of colour Doppler imaging improves safety of procedures and allowed to perform ultrasound guided biopsy in 73 patients. On the basis of our experience we state that colour Doppler sonography guided percutaneous fine needle biopsy of the liver is useful, sufficient and safety diagnostic method of abscesses, cysts and malignant tumours of the liver.     

Genomic imprinting and its role in Prader-Willi and Angelman syndromes

Published and our own data, included in the CHRODYS database, on the dependence of phenotypic abnormalities in mono-, di-, and trisomics at human chromosome 15 on its parental origin are reviewed. The concept is confirmed that Prader-Willi and Angelman syndromes result from the combined effect of gene or chromosome mutations impairing the expression of syndrome-specific genes and from genomic imprinting, i.e., repression of corresponding genes received from one of the parents.     

Prader-Willi syndrome

BACKGROUND: First described in 1956, Prader-Willi syndrome is a neurogenetic condition characterized by infantile hypotonia, hypogonadism and obesity. Mental deficiency, behavioral abnormalities, and obvious dysmorphic features are frequently found as well. It is a relatively common condition, with an incidence estimated to be between 1 in 10,000 to 25,000 live births. Few studies have been published that investigated the ocular defects associated with this syndrome. METHODS: This case report discusses the systemic and oculo-visual abnormalities of a 34-year-old white male enrolled in the Easter Seal Society of Metropolitan Chicago/Illinois College of Optometry Eye Care and Treatment Program. Examination techniques commonly used for patients with cognitive/developmental dysfunctions were utilized. RESULTS: Our findings include ocular hypopigmentation with reduced visual acuity, a myopic refractive error, exotropia, corneal abnormalities, glaucoma, and other ocular and systemic health abnormalities. CONCLUSIONS: Reported ocular findings for patients with Prader-Willi syndrome include iris hypopigmentation with depressed visual acuity, moderate to high refractive error, and strabismus. Individual patients with this syndrome have also been reported with cataracts, congenital ocular fibrosis syndrome, diabetic retinopathy, and congenital ectropion uveal. The numerous ocular, systemic, and functional abnormalities of patients with Prader-Willi syndrome make it mandatory that all routinely receive primary optometric vision care.     

Prader-Willi syndrome.

Although known for its distinctive food-related behaviors, Prader-Willi syndrome is a multisystem disorder with genetic, developmental, and behavioral features. Two separate and distinct eating disorders are noted: initial feeding difficulties and failure to thrive, and later overeating. Additional outcomes observed with this disorder include hypotonia, obesity, developmental/cognitive disabilities, and significant maladaptive behaviors. Symptoms vary in complexity across age and individuals. This necessitates multidisciplinary approaches to interventions across the life span to address medical, developmental, and behavioral issues. School psychologists have a vital role to play in assessment and consultation for individuals with this syndrome, their families, and school staff. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adverse effects of vigabatrin in Angelman syndrome

New antiepileptic drugs designed for enhancing GABAergic inhibition, such as vigabatrin (VGB) may be effective in Angelman syndrome (AS), because associated convulsions could be related to a reduced GABA-receptor density or receptor abnormality. From our preliminary experiences in four children with AS treated with VGB, we conclude that it may induce and increase seizures in patients with AS.     

Molecular and clinical study of 61 Angelman syndrome patients

This is the first study of of posttraumatic stress symptoms in parents (24 mothers and one father) of children with burns. The purpose of the study was to determine what factors relate to parental posttraumatic stress disorder (PTSD). Because the sample is all mothers, except for one father, the conclusions are about mothers. Through use of the Structured Clinical Interview for DSM-III-R, symptoms were determined as occurring from the time of the burn injury until 1 month before the interview (past), 1 month before the interview only (present), or from the date of the burn trauma up to and including 1 month before the interview (past and present). By Structural Clinical Interview criteria, 52% of the mothers had past PTSD, with four (31%) of those mothers having present PTSD symptoms. Eleven mothers and the one father reported neither past nor present PTSD. Multiple regression analysis revealed that larger burns were more strongly related to present PTSD symptoms than were proximity, social support, or perceived stress. Additional findings indicated that mothers with more than one child burned and those mothers who were burned themselves met diagnostic criteria for PTSD. Implications are that posttraumatic stress symptoms can be disruptive to a mother feeling capable of caring for her child with burns after the injury. Individual and group therapy during and after a child's hospitalization may be useful for mothers to reduce stress and to develop better coping skills.     

Laurence-Moon-Biedl syndrome (?) and Prader-Willi syndrome (?) in a single family

Mental retardation, hypogonadism, obesity, and abnormal blood sugar regulation were common findings in two siblings. In addition, the 17-year-old female patient showed short stature, muscular hypotonia in infancy, and small hands with tapering fingers suggesting Prader-Willi syndrome, and the 12-year-old male patient showed retinitis pigmentosa, normal height, and normal muscular tonicity suggesting Laurence-Moon-Biedl syndrome, though polydactyly was absent. Possible consideration was discussed.     

The neonatal presentation of Prader-Willi syndrome revisited

We describe 6 newborns evaluated for hypotonia, later diagnosed with Prader-Willi syndrome despite the absence of the classical neonatal features of this syndrome. Specific genetic testing for Prader-Willi syndrome should be considered for all neonates with undiagnosed central hypotonia even in the absence of the other major features of this syndrome.     

Prader-Willi syndrome and a bisatellited derivative of chromosome 15

A de nova bistaellited derivative of chromosome 15, inv dup (15) (pter leads to q11 or 12::p11 or q11 or 12 leads to pter), was identified by multiple banding techniques in a patient with Prader-Willi syndrome. A comparison of familial no. 15 short arm polymorphisms indicated that the extra chromosome was the result of a non-sister chromatid exchange between the paternal no. 15 homologs prior to or during meiosis.     

Diagnosis of Prader-Willi syndrome by reverse transcriptase polymerase chain reaction

To approve Prader-Willi syndrome by molecular diagnostic assay, polymerase chain reaction of reverse-transcribed RNA was introduced by which indirect information can be gained on all known forms of the mutation. In this pilot study, 4 patients and 16 healthy control individuals were examined. Although the different mutation forms can not directly by identified by this approach, it is a useful and reliable test to confirm the clinical diagnosis of the Prader-Willi syndrome, and to screen for the syndrome in patients who present with only a few typical features.     

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.     

Food preferences in Prader-Willi syndrome, normal weight and obese controls

OBJECTIVE: The aim of this work was to assess the specific food type (high carbohydrate, high fat, high protein) preference profiles of individuals with Prader-Willi syndrome (PWS), obese controls and normal weight individuals. DESIGN: Subjects tasted a food predominantly high in carbohydrate, a food predominantly high in protein and a food predominantly high in fat over repeated trials and indicated their most preferred, second preferred and least preferred foods. Specific items tested on a given trial were counterbalanced in a block randomized fashion. SUBJECTS: These were 12 individuals with Prader-Willi syndrome, 12 matched obese controls (obese, but otherwise normal) and 14 normal weight subjects. MEASUREMENTS: The basic data were expressed as a proportion of each food type selected as most preferred over the total 27 trials. RESULTS: PWS subjects preferred high carbohydrate foods over high protein foods and high protein foods over high fat foods. These subjects demonstrated a statistically reliable difference in preference for high carbohydrate foods over high fat foods. However, normal weight and obese control subjects demonstrated no difference in food preferences. The only significant between-group comparisons were between PWS subjects and obese controls, with the PWS group showing a significantly greater preference for high carbohydrate foods than obese controls. CONCLUSIONS: The obesity of PWS was shown to have a significant and distinctly different food preference profile from normal weight and obese controls. The differences in food preference between the obese PWS and non-PWS subjects is in accord with the growing recognition of functional subgroups within the obese population, that may have not only differing underlying etiologies, but also distinct behavioral profiles of ingestion.