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Research Notes: PWS Abstracts - 1980-1989[ 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996 | 1995 | 1994 | 1993 | 1992 | 1991 | 1990 | 1980-1989 | 1979 and prior ] J Bone Joint Surg Br. 1989 Aug. There is a high incidence of spinal deformity in children with the Prader-Willi syndrome. We have encountered major complications following spinal surgery in this condition. We report our experience and conclude that spinal surgery is a formidable undertaking and the risks should be appreciated by the surgeon and the parents. Am J Hum Genet. 1989 Jul. In order to determine the frequency and characterization of hypopigmentation in Prader-Labhart-Willi syndrome (PLWS), clinical, cytogenetic and biochemical findings are reported in 56 PLWS individuals. Forty-eight percent of the individuals with PLWS met the criteria for hypopigmentation. Hypopigmentation in PLWS individuals appears to be as common as previously recognized features such as behavioral problems and dental abnormalities. Significant differences in hair color, sun sensitivity, and complexion were found between those PLWS patients with the chromosome 15 deletion and those with normal chromosomes. Individuals with the deletion frequently had lighter hair color, more sun sensitivity, and fairer complexion than did either other family members or nondeletion PLWS patients. No significant differences in biochemical findings (phenylalanine, tyrosine, catecholamines, or beta-melanocyte-stimulating hormone) were found between deletion and nondeletion PLWS patients or between hypopigmented and normally pigmented patients. The data suggest that a gene(s) controlling the activity of tyrosinase or other enzymes required for melanin production is located on proximal 15q. J Ment Defic Res. 1989 Jun. A case of Prader Willi Syndrome who suffered from hypothyroidism is described. This patient on cytogenetic examination was found to have Mosaic 46,XX/46,XX,del(15)(q11.1q11.2) karyotype. Am J Hum Genet. 1989 Jun. Prader-Willi syndrome (PWS) is a multiple-anomaly disorder in which 50%-70% of cases are associated with a de novo interstitial deletion [del 15(q11-13)] on prometaphase cytogenetic analysis, the remainder having apparently normal chromosomes. In most instances, the paternally derived chromosome has become deleted in the affected child, suggesting the possibility of a predisposing environmental factor. Strakowski and Butler found an increased incidence of paternal periconceptional employment in hydrocarbon-exposing occupations in this population. This observation may suggest a causal relationship to PWS. To determine whether this association may distinguish the cytogenetically different groups, we identified 81 patients with the disorder who were physically and cytogenetically examined in three centers, and we compared the frequency of possible periconceptional occupational hydrocarbon exposure between fathers of patients who demonstrate a 15q deletion and those who do not. There was no statistically significant difference between the cytogenetically different groups. In both groups, approximately half of the fathers had been employed in hydrocarbon-exposing jobs. These findings suggest lack of etiologic heterogeneity between the cytogenetically different groups for PWS and affirm the need to seek submicroscopic deletions through molecular genetic studies. These data also provide additional evidence that hydrocarbon exposure among fathers of children with PWS may be causally related to the disorder, and they also suggest the need for more accurate assessment of exposure via a large, controlled study. Srp Arh Celok Lek. 1989 May-Jun. An 11-old boy with Prader-Willi syndrome and partial epilepsy was reported. Muscular hypotonia in early infancy was extreme and developmental milestones were retarded, especially walk and speech. He achieved these landmarks within three years. The first seizure disorder was seen in the 9th year. The patient was characterized by hypotonic musculature, severe mental retardation, obesity (gynaecomasty, excess of fat on the thighs, the abdomen and the trunk), hypogonadism (a minute penis, hypoplastic scrotum and cryptorchidism). Apart from these characteristics, the patient presented some minor morphological anomalies (turicephalic skull, high-arched palate, abnormally shaped pinnae, clinodactily, defects on teeth enamel), and some skeleton and joint anomalies (small feet, kyphosis, lumbar lordosis, knock-knee, flat foot). Speech retardation, behaviour disturbance and inappropriate emotional reaction were noted. Karyotype was normal. Dermatoglyphic analysis showed some significant qualitative and quantitative characteristics. An abnormal glucose tolerance curve was obtained. Electroencephalogram showed an irritative paroxysmal discharge with primary focal activity in frontal-temporal cortical regions of the brain left hemisphere. Rev Esp Anestesiol Reanim. 1989 May-Jun. No abstract available. Doc Ophthalmol. 1989 Apr. Oculocutaneous, electrophysiological, and cytogenetic factors were evaluated in 14 patients with Prader-Willi syndrome and in three controls, two albinos and a normal observer. In a substantial number of PW patients chromosomal anomalies, particularly deletions of the long arm of chromosome 15 as well as hypopigmentation of hair, skin, and eye have been identified. In the genetic condition of albinism, hypopigmentation related to neural ectoderm derivatives is associated with reduced visual acuity, foveal hypoplasia, and aberrant retinogeniculocortical projections. The latter can be observed by visual evoked potential (VEP) assessment of hemispheric response symmetry. To determine the possible neural ectodermal origin of hypopigmentation and its involvement in ocular development and optic pathway integrity, the potential distributions of the pattern onset/offset VEP were examined. Our results show hypopigmentation in 13 of our 14 PW patients and a chromosome abnormality in 6; no correlation between these two features was found. None of the PW patients showed the characteristic contralateral hemispheric asymmetry seen in albinism. On the other hand their VEP profiles were found to be atypical, rendering waveform and cortical topography difficult to interpret. Analysis suggests that in the absence of VEP evidence for optic pathway misprojection, PW hypopigmentation is probably of neural crest origin. Dev Med Child Neurol. 1989 Apr. The authors retrospectively evaluated the diagnoses at four months of age for 48 individuals with known Prader-Willi syndrome. 15 had been diagnosed as having cerebral palsy, and at four months only two of the 48 had been correctly diagnosed as Prader-Willi syndrome. 11 (23 per cent) had had birth asphyxia, compared with an expected rate of 1 per cent. Other perinatal features which occurred more frequently than expected included breech presentation, decreased fetal movements and prolonged gestation. Failure to make an early diagnosis of Prader-Willi syndrome often results in later disability being blamed on the birth process, when instead the child's neonatal problems are secondary to a prenatal condition. Clin Genet. 1989 Mar. Four patients with Prader-Willi syndrome, diagnosed in the neonatal period and followed during the first year of life, are reported. There were three males and one female. All four patients presented with hypotonia and distinct craniofacial dysmorphism. Prometaphase chromosome analysis showed interstitial deletion of 15q in all of them. The placentae and umbilical cords were examined in three of the patients and found normal. Electromyography done in the neonatal period suggested primary myopathy. Height, weight and head circumference were normal at birth in all patients. Hand and foot measurements showed normal size at birth and during the first year of life. Aust Paediatr J. 1989 Feb. Twenty-two individuals with Prader-Willi Syndrome in New South Wales were surveyed. The results show that males were diagnosed at a significantly earlier age than females and suggest a recent trend towards earlier diagnosis. The advantages of early diagnosis are discussed. In those in whom cytogenetic studies had been performed, 47% were found to have a deletion involving chromosome 15q11-13. Profound neonatal hypotonia had been present in all cases. Obesity became apparent between 1.5 and 10 years (mean = 3.8 years). Facial dysmorphism was reported in 83% and acromicria in 100%. Sixty-two per cent of subjects were regarded as less pigmented than first degree relatives. Cognitive assessments were performed on nine subjects. Two (22%) were functioning in the normal range of intelligence. Behaviour problems, both food-related and non-food-related, were present in the majority and placed considerable stress on the family caring for the individual with Prader-Willi Syndrome. J Speech Hear Disord. 1989 Feb. The case study follows the development of phonologic abilities in a child with Prader-Willi syndrome from age 2:7 to 6:1 during a period in which she was enrolled in language and phonologic remediation. Changes in her phonetic inventory, in the set of phonemes used correctly, and in phonologic processes are described. Although her phonologic system appeared to parallel those of normally developing children in many ways, some unusual sounds and patterns of usage were also seen. Because the effect of the treatment program on the development of her phonologic system cannot be adequately determined, clinicians should use caution when generalizing these results to other children with this syndrome. J R Soc Med. 1989 Jan. A survey of 32 adult females and 31 adult males with Prader-Willi syndrome (PWS) shows that sleep disorders (including excessive day and night time sleep) and behavioural abnormalities, (temper tantrums and deliberate picking of sores) are common. These abnormalities are not related to the degree of obesity or to each other. Speech disorders also occur. Intelligence quotients are often within the normal range. Pancreas. 1989. Children with Prader-Willi syndrome (PWS) are characterized by obesity, hyperphagia, hypogonadism, and mental retardation with underlying hypothalamic dysfunction and are known to have blunted or absent pancreatic polypeptide (PP) secretion in response to protein meals. In this communication, adults (26 +/- 3 years of age) with PWS were compared with age-matched normal obese and normal weight controls in regards to plasma glucose, insulin, PP, cholecystokinin (CCK), cholesterol, and triglyceride after a high protein meal. Compared with normal weight controls, adults with PWS showed a smaller and delayed rise in plasma insulin, and relatively smaller and delayed PP elevation whereas obese controls revealed hyperglycemia, markedly higher insulin, and moderately higher PP, cholesterol, and triglyceride levels than those with PWS. There was a small increment of CCK levels after a protein meal in all groups of adults. After a protein meal, the molar ratio of PP to CCK doubled in normal weight and PWS groups, and this ratio tripled in the normal obese group, suggesting no reduced PP secretion in PWS in response to CCK stimulation. PP hyposecretion in PWS thus appears to be a part of multiple endocrinopathy associated with hypothalamic dysfunction. Minerva Anestesiol. 1988 Dec. No abstract available. Rev Esp Anestesiol Reanim. 1988 Jul-Aug. No abstract available. J Pediatr Ophthalmol Strabismus. 1988 May-Jun. Forty-six patients with Prader-Willi syndrome were examined to determine the incidence and character of ocular abnormalities. All patients met clinical criteria for this syndrome including infantile hypotonia, hypogonadism, truncal obesity, intellectual impairment, dysmorphic facies, and short stature. Thirty-two patients had best corrected visual acuities between 6/6 and 6/9 in each eye. Seven patients (15%) had myopia greater than -3.75 diopters. Nineteen (41%) patients had astigmatism of 1.25 diopters or greater. Amblyopia of strabismic, anisometropic, or ametropic etiology was present in 11 (24%) of the patients. Strabismus was present in 25 (54%) patients: 22 (48%) patients had esotropia and three (7%) had exotropia. Nine patients either received or required strabismus surgery. Thirty-three percent of the patients examined for iris transillumination defects had this finding. This study represents the first large series of patients with Prader-Willi syndrome to undergo detailed ophthalmologic evaluation. Recognition of this syndrome is important because of the high incidence of potentially treatable ocular problems. Metabolism. 1988 Feb. Patients with Prader-Willi syndrome are frequently obese. To determine if obesity is partially explained by a low energy expenditure, we compared total daily energy expenditure, basal metabolic rate, and body composition in Prader-Willi patients with obese controls. Total energy expenditure was measured by doubly labeled water, basal metabolic rate was measured by respiratory gas analysis using an open-system canopy design, and body composition was calculated from total body water determinations using 18O labeled water. In six Prader-Willi subjects, basal metabolic rates were normal when compared on the basis of fat free mass, but not body surface area or height, weight, and age. Ten Prader-Willi subjects (8 to 24 years-old) had a total daily energy expenditure (+/- SD) of 1,980 +/- 580 kcal/d, which was 47% less than their obese controls (3,700 +/- 820 kcal/d). When normalized for their smaller fat free mass and body mass, however, the difference was only 14% (P less than .01). The results indicate that the low energy expenditures in Prader-Willi syndrome are mostly due to the small fat free mass in these patients and not due to any difference in energy efficiency at the cellular level. Prader-Willi subjects who had lost weight and were at or near weights appropriate for their heights were still 30% to 40% body fat. Because this excess fat was not evident from skinfold measures, usual anthropometric measures were not reliable indicators of total body fat in these subjects. Brain Dev. 1988. A young boy showed features of Prader-Willi syndrome including hypotonia, cryptorchidism, a mildly dysmorphic facial appearance, a high-arched palate and an open triangular-shaped mouth, but had additional symptoms such as simian creases and multiple joint ankylosis in early infancy. Deletion of the long arm of chromosome 15(q11.2 to q13) was recognized. A muscle biopsy specimen showed variation in fiber size with hypertrophic type 1 fibers, type 2 fiber smallness, type 2B fiber paucity and an increased number of type 2C fibers. At the age of 4 1/2 years, he still showed severe developmental delay with severe muscle hypotonia, weakness and emaciation. Int J Obes. 1988. We report the first prospective longitudinal study of dietary intake, weight, height, and skinfold measurements during the early phase of four Prader-Labhart-Willi syndrome (PLWS) individuals (two males and two females). Although caloric intake ranged from 80 to 90 percent of recommended daily allowance during our study of the four PLWS infants, obesity still occurred. Our findings suggest that the onset of obesity in PLWS individuals occurs earlier than previously thought in spite of reduced caloric intake. The infants in our study reached the obese range judged by skinfold measurements greater than the 85th centile at an early age and before they were considered heavy based on weight for height criterion. We propose that skinfold measurements should be obtained on all individuals with PLWS and obesity judged by this criterion. Am J Med Genet. 1987 Dec. Clinical observations and parental reports on the behavior of Prader-Willi syndrome (PWS) patients suggest the development of a wide variety of psychiatric disorders as the PWS child enters adolescence. Documentation of these emotional disorders remains unsystematic. Here we describe the results of administering the Survey Diagnostic Instrument (SDI) to the parents of 35 PWS adolescents. The questionnaire data were supplemented by additional selected demographic and clinical data. The SDI is a 134 item questionnaire filled out by one parent. It screens for the DSM-III criterion-based diagnostic categories of neurosis (dysphoric, compulsive, anxious), somatization, conduct disorder (antisocial, violent), and hyperactivity. The following diagnostic pattern resulted: neurosis, dysphoric, (1 probable); neurosis, compulsive, 3 (6 probable); neurosis, anxious, 4 (and 10 probable); somatization, 0; conduct disorder, violent 0; conduct disorder, antisocial, 0; hyperactivity, 1 (and 1 probable). An odds ratio algorithm is used to uncover possible predisposing factors, and the results are discussed in the context of organic versus psychiatric causes. Am J Med Genet. 1987 Dec. Inability to vomit has been cited as characteristic of Prader-Willi syndrome (PWS). Although post-prandial vomiting after gastric by-pass surgery has been reported, neither vomiting under "typical" circumstances or rumination have been described. Prompted by the discovery of several cases of vomiting and rumination, a questionnaire was sent to members of the PWS Association. Approximately 36% (113/313) of affected individuals reportedly experienced at least one episode of vomiting. Induced vomiting was unsuccessful in 9 of 14 cases in whom results were known. However, no complications of Ipecac were reported. We suggest that there is an alteration in the physiologic set-point at which vomiting occurs, leading to a decreased propensity to vomit. Liberal and strict definitions of rumination yielded 15.7% and 10.2% positive responses, respectively. Rumination was associated with a history of vomiting. Enamel deterioration consistent with rumination has been observed, and such changes should be looked for in all PWS children. In several instances, rumination was found to decrease when very strict weight control was lessened. Certain individuals may ruminate under too strict a weight control program, and weight control goals should be evaluated to achieve a reasonable compromise between ideal weight and obesity. Vomiting and rumination do not rule out the diagnosis of PWS. Am J Med Genet. 1987 Dec. We have studied steroid sulfate conjugates in serum samples from 17 children with Prader-Willi syndrome (PWS) by extraction, enzymatic hydrolysis and chromatography of the hydrolysed, free steroids. The chromatograms in patients with PWS can be divided into 2 classes. Ten (4 with the deletion on chromosome 15 and 6 without) of 17 had a normal pattern with dehydroepiandrosterone (DHEA) as the only steroid detected. However, 7 out of 17 (3 with the deletion and 4 without) had a very different pattern. The chromatogram derived from these hydrolysates had 5 major peaks. One of these was DHEA; a second peak was tentatively identified as 16 alpha-hydroxy-DHEA on the basis of column retention time and immunoreactivity. The remaining 3, more polar, compounds have not yet been identified. The presence of unusual steroid sulfoconjugates in serum may correlate with other features of PWS and may be the basis for dividing PWS into two separate disease states: a) PWS-1 associated with DHEA-S as the only sulfo-conjugate and b) PWS-2 associated with unusual sulfo-conjugates. One interesting possibility is that these sulfo-conjugates may have a hormonal function, even though no function has yet been recognized for DHEA-S. Then, PWS may be the common clinical manifestation of a variety of different defects in the sulfo-conjugate metabolic pathway. Am J Phys Anthropol. 1987 Dec. A study of anthropometric variation and craniofacial growth in individuals with the Prader-Labhart-Willi syndrome (PLWS) illustrates the utility of anthropometry in clinical evaluation and research. Anthropometric measurements, including head length and breadth, minimum frontal diameter, and head circumference, were obtained on 38 PLWS individuals (21 with chromosome 15 deletions) with an age range from 2 weeks to 39 years. No anthropometric differences were found between the two chromosome subgroups. A relative deceleration in the growth of certain craniofacial dimensions (head circumference and length) is suggested by the negative correlations between age and Z-scores for the measurements. Raw values for minimum frontal diameter and head breadth were near or below the 5th percentile curve, while almost all values for head length and circumference fell within normal limits. The data support suggestions that dolichocephaly be considered an early diagnostic feature of PLWS. Furthermore, the status of narrow bifrontal diameter as a major feature of PLWS is confirmed. Am J Med Genet. 1987 Dec. A 26-year old white male with Prader-Willi syndrome (PWS) and non-insulin-dependent diabetes mellitus presented with asymptomatic bilateral lower limb swelling. An electrocardiogram was consistent with an inferior wall myocardial infarction of unknown age and a graded exercise test using the Bruce protocol was consistent with inferolateral ischemia. Subsequent cardiac catheterization showed severe, inoperable, three-vessel coronary artery disease. Atherosclerotic coronary artery disease in PWS has been documented only once in the literature, and then only postmortem. This case provides further (and for the first time, premortem) documentation that premature atherosclerotic coronary artery disease may play an important but presently unrecognized role in the morbidity and mortality in PWS. J Autism Dev Disord. 1987 Sep. This study investigated the relationships between mineral elements and Prader-Willi syndrome (PWS) and determined which minerals, if any, separated a group of PWS individuals (N = 19) from a non-PWS mentally retarded control group (N = 60). The PWS group had significantly raised hair magnesium levels and significantly lower hair silicon levels than controls. The PWS group was also elevated in hair calcium, magnesium, and copper in relation to laboratory standards, while their hair silicon, chromium, and lithium levels were deficient in relation to laboratory norms. Discriminant function analysis revealed that by using 16 hair minerals subjects could be correctly classified as PWS or non-PWS with 89.5% and 95.0% accuracy, respectively. It is concluded that continuing research is needed to study the relationship between mineral element patterns and PWS. Wiad Lek. 1987 May 15. No abstract available. Am J Hum Genet. 1987 May. Cutaneous and ocular pigmentation were evaluated in 29 individuals with the Prader-Willi syndrome (PWS). Criteria for hypopigmentation included the presence of type I or II skin, the lightest skin type in the family by history, and iris translucency on globe transillumination. On the basis of these criteria, 48% of the PWS individuals were hypopigmented. The presence of hypopigmentation correlated with a small interstitial deletion on the proximal long arm of chromosome 15; however, this deletion was also found in individuals who did not meet the full criteria for hypopigmentation. Hairbulb tyrosinase activity and glutathione content, as well as urine cysteinyldopa excretion, were low in PWS individuals with and without hypopigmentation and did not separate these two groups. We conclude that hypopigmentation is found in a significant proportion of individuals with PWS and that the hypopigmentation may be associated with a deletion of the long arm of chromosome 15. The mechanism for the hypopigmentation is unknown. J Pediatr Ophthalmol Strabismus. 1986 Jul-Aug. We report an 11-year-old boy with both the congenital ocular fibrosis and the Prader-Willi syndromes. Since birth he has had bilateral blepharoptosis and fixed ocular misalignment in downward gaze. Pathological examination of the extraocular muscles showed replacement by fibrous tissue. Additionally, the child had the typical clinical features of the Prader-Willi syndrome including mental retardation, hypotonia, short stature, hypogonadism, and obesity. The Prader-Willi syndrome has been consistently associated with interstitial deletions of the long arm of chromosome 15. Although our patient appeared to have normal chromosomes, he may indeed have an undetectable deletion which may be responsible for both syndromes. We believe that the gene(s) for the congenital ocular fibrosis syndrome may be located near the gene(s) for the Prader-Willi syndrome on the long arm of chromosome 15. JAMA. 1986 Jun 20. A patient with Prader-Willi syndrome and unilateral congenital ectropion uveae with glaucoma was found to have factor XI deficiency and reduced levels of serum luteinizing hormone, follicle-stimulating hormone, and testosterone. Administration of gonadorelin (LH-RH) increased serum levels of luteinizing hormone and follicle-stimulating hormone, while clomiphene citrate had no effect, suggesting a primary hypothalamic defect. Patients with congenital ectropion uveae should be followed up for the development of both glaucoma and neural crest disorders. N Engl J Med. 1986 Jun 19. Patients with oculocutaneous or ocular albinism have misrouting of optic fibers, with fibers from 20 degrees or more of the temporal retina crossing at the chiasm instead of projecting to the ipsilateral hemisphere. Misrouting can result in strabismus and nystagmus. Because patients with the Prader-Willi syndrome may also have hypopigmentation and strabismus, we wondered whether they too might have misrouting of optic fibers. We therefore studied six patients with Prader-Willi syndrome selected for a history of strabismus, using pattern-onset visually evoked potentials with binocular and monocular stimulation to look for evidence of misrouted retinal-ganglion fibers. Four had hypopigmentation, and three of these four had abnormal evoked potentials indistinguishable from those recorded in human albinos. The two with normal pigmentation had normal responses. These findings indicate that patients with Prader-Willi syndrome who have hypopigmentation have a brain abnormality characterized by misrouting of retinal-ganglion fibers at the optic chiasm--a finding previously reported only in forms of albinism. Acta Endocrinol Suppl (Copenh). 1986. In 3 groups of 8 children and adolescents each with Prader-Willi-Labhart's Syndrome (PW-S), obese patients matched for body weight (control I), and normal weight subjects matched for pubertal stage (control II) plasma concentrations of melatonin, cortisol, growth hormone (hGH), insulin, gonadal hormones, and gonadotropins were measured every 1 to 4 hours in 24-hour-profiles. All hormones were determined by radioimmunoassay. The specific melatonin antibody was raised in rabbits. Criteria of the melatonin assay were as follows: detection limit for plasma concentrations of 13 pg/ml, intraassay and interassay variations: 8.4 and 11.2%, respectively. PW-S-patients showed cortisol fluctuations within normal limits. hGH was lower than 5 micrograms/l even during sleep, insulin ranged between 5 and 170 mU/l, and no excessively high glucose levels were found. Estradiol and testosterone were low for age and for pubertal development in all patients except in two girls. Basal LH and FSH levels were in the low normal range and showed sluggish response to LHRH. Plasma melatonin was low during the day, increased at mid-night and peaked at 3 a.m. Melatonin levels in PW-S were not significantly different from those in both control groups. We concluded that the impairment of gonadotropin secretion in patients with PW-S is not due to elevated levels of plasma melatonin. Appl Res Ment Retard. 1986. Although most Prader-Willi syndrome children perform in the mentally retarded ranges on standardized IQ tests, it is not known if their cognitive impairments are global in nature or if they exhibit a particular pattern of strengths and weaknesses in their psychological capacities. To examine this question, a cohort of children suffering from Prader-Willi syndrome was administered a battery of neuropsychological tests. The results indicated that, relative to other cognitive capacities assessed, particularly severe deficits were noted on tasks that involved information processing using the auditory modality. No differences in cognitive capacity were found between children with a number 15 chromosome defect and those with a normal karyotype configuration. Based on these initial findings, it appears that the clinical diagnosis of Prader-Willi syndrome is more important than a karyotype configuration in understanding these youngsters' manifest cognitive deficits. Clin Genet. 1986 Mar. The apparently rare cytogenetic abnormality of partial trisomy 15 was diagnosed by the authors in a patient presenting with developmental retardation, macrocephaly with ventricular enlargement and prominent subarachnoid spaces, hypotonia, low-set ears, hyperextensible wrists and hands, high arched palate, tapering fingers, right esotropia, and bilateral metatarsus adductus. Clinical findings in this case are similar to previously reported cases of proximal duplications of chromosome 15 and bear some similarity to the Prader-Willi syndrome. However, our patient did not have the severe hypotonia, early failure to thrive, or genital abnormalities seen in classical Prader-Willi syndrome. This case supports the theory that a variety of cytogenetic aberrations in proximal 15q can cause a "Prader-Willi-like" syndrome. Increased clinical suspicion is needed when patients are seen with hypotonia, retarded development and mild dysmorphism if the variety of phenotypes are to be delineated. No To Shinkei. 1985 Nov. An autopsy case of 23-years-old man with Prader-Labhart-Willi syndrome (P-L-W syndrome), who had died by acute renal failure due to burn injury, was reported. P-L-W syndrome was constituted by hypotonia, hypogonadism, hypomentia, obesity and other minor anomalies, however, CNS anomaly had not been reported. The patient sat at 3 years of age, walked at 4 years old, began to utter single words at 3-4 years, and he began to obese at 4 years of age. He fulfilled the condition of P-L-W syndrome mentioned above. On his age 15, laboratory findings on admission revealed remarkable diabetic pattern by oral glucose tolerance test and intelligence quotient was 28, and the other laboratory findings were within normal limit. During his clinical history, complications of diabetes mellitus, such as diabetic retinopathy and neuropathy, were aggrevated, and upstanding and gait were impossible at 20 years of age. On his age 23, he suffered from burn injury at left lower extremity and he fell in acute renal insufficiency. Five autopsy cases of P-L-W syndrome have been reported so far, however, CNS anomaly has not been observed. Following anomalies in our case was recognized, such as shortness of the frontal lobe, partial micropolygyria of the dentate nucleus, heterotopia of the inferior olivary nucleus, ectopia of Purkinje cell in the molecular layer, heterotopia of middle sized neuron in the deep white matter of the cerebellum and large number of residual nerve cells in the cerebral subcortical white matter. Lancet. 1985 Jan 5. No abstract available. Helv Paediatr Acta. 1984 Oct. Hum Nutr Appl Nutr. 1984 Aug. The nutritional status and growth of infants in the pre-obese phase of the Prader-Willi Syndrome has not previously been investigated. In this study the daily energy and protein intake of a male infant with this syndrome was measured from the 21st to the 330th day of life, together with weekly weight and monthly height measurements. The primary source of food was expressed breast milk. Daily energy intake was 29-66 per cent below recommended amounts. Protein intake did not exceed 12 g per day. Body weight remained at or below the third centile with a marked downward trend at 6 months. The symptoms associated with the Prader-Willi Syndrome result in a lack of physical maturity; poor feeding exacerbates this situation. Arch Neurol. 1984 Mar. Nine patients with the Prader-Willi syndrome, ranging in age from 3 to 21 years, were examined clinically as well as studied in the sleep laboratory. They had striking disturbances of sleep-wakefulness patterns. All patients except one had the symptom of excessive daytime sleepiness. The most striking finding was the presence in five patients of rapid-eye-movement (REM) sleep occurring at sleep onset (SOREM). None of the patients had the condition of sleep apnea. One patient, however, demonstrated severe hypoventilation during REM sleep; the lowest value recorded for O2 saturation was 40%, with a consistent value below 50% for as long as ten to 15 minutes. Previous findings have indicated that the Prader-Willi syndrome is of hypothalamic origin. We hypothesize that both the SOREM and O2 desaturation findings in our patients with the Prader-Willi syndrome are also a result of hypothalamic changes. Arch Neurol. 1984 Jan. We studied the histochemical characteristics of muscle in five hypotonic infants. A number of different patterns of disproportion in the sizes and numbers of type 1 and type 2 fibers were found. In three cases, type 1 fibers were smaller than type 2 fibers and type 2b or 2c fibers were largest. In one case, type 2 fibers were smaller than type 1 fibers and were reduced in number, while in a case of Prader-Willi syndrome there was a preponderance of type 2 fibers that were smaller than type 1 fibers. Type 2c fibers were increased in number in all but one case. We postulate that these various patterns of fiber-type disproportion are the result of altered neural influences leading to impaired maturation of type 1 or type 2 motor units. Aust Paediatr J. 1983 Dec. Fourteen children with the Prader-Willi syndrome have been managed at the Royal Alexandra Hospital for Children between the years 1964-1980--twelve male, two female. Six male children developed features of the obesity hypoventilation syndrome. The age of onset of this complication ranged from 4.0 to 12.6 years. With one exception those children with the obesity hypoventilation syndrome were more obese than those without it. At the time of onset of the syndrome, five of six patients had weights greater than or equal to 6.5 standard deviations above ideal body weight. Those children without the obesity hypoventilation syndrome had a range of standard deviations 1.0 to 4.2 above the ideal body weight. In four of six cases weight reduction and a cardiac failure regimen resulted in reversal of the obesity hypoventilation syndrome. With two of the six children there had been cardiomegaly and increased pulmonary venous vascularity on x-ray at a chronological age of three months. Two of the six children died. Acta Endocrinol (Copenh). 1983 Nov. The Prader-Willi syndrome is among other features characterized by obesity and a high prevalence of glucose intolerance. The fasting plasma insulin concentration and the insulin response to glucose are often increased, indicating some insulin resistance in this disease. To investigate whether this could be due to an insulin receptor defect 7 patients with Prader-Willi syndrome, 10 normal weight subjects and 8 obese subjects were tested for the binding of [125I]insulin to monocytes. Monocytes from patients with Prader-Willi syndrome bound significantly less insulin than cells from normal subjects (P less than 0.01). However, no difference was found between Prader-Willi patients and the obese controls (P greater than 0.1). It is concluded that the insulin resistance found in Prader-Willi patients, similar to that found in obese subjects, in part, may be explained by an insulin receptor defect on target cells for insulin action. J Clin Endocrinol Metab. 1983 Nov. Children with hyperphagia and obesity of Prader-Willi syndrome (PWS) have previously been shown to have blunted pancreatic polypeptide (PP) response to low protein meal stimulation. To evaluate the effects of various protein challenges on PP release in children with PWS, we administered both a low protein (0.2 g/kg) and a high protein (2.0 g/kg) meal stimulation test to 12 children previously diagnosed as having PWS and to an age- and weight-matched group of 19 obese but otherwise normal children. Serum samples were collected just before and for 3 h after meal ingestion. The mean (+/- SD) age was 11.7 +/- 4.2 yr for the PWS group and 10.3 +/- 3.8 yr for the obese group (P = 0.323). The percent ideal body weight for height for the PWS group (mean +/- SD 186 +/- 48%) was not significantly different from the percent ideal body weight for height for the obese group (174 +/- 35%; P = 0.421). Peak PP responses were significantly less for the PWS group than for the obese group for both the low and high protein meal stimulations. The mean (+/- SE) peak PP response with the low protein meal was 76.1 +/- 13 pg/ml for the PWS group and 302 +/- 93 pg/ml for the obese group (P less than 0.05). The mean peak response with the high protein meal was 181 +/- 51 pg/ml for the PWS group and 581 +/- 127 pg/ml for the obese group (P less than 0.01). Glucose rises were similar for both tests, although the PWS group did have a slightly smaller rise in glucose after the low protein stimulation than was observed in the obese group. The insulin response was also significantly less for the low protein meal in the PWS group compared to the low protein insulin response of the obese group. There were no significant differences in the insulin responses observed in both groups with the high protein meal test. This study confirms our previous observation and suggests that many children with PWS have a functional deficiency of PP. Our current study demonstrates that this condition is not a result of their obese condition or an alteration in their response threshold to protein. J Behav Ther Exp Psychiatry. 1983 Sep. Behavioral interventions have had limited success in managing the chronic hyperphagia and obesity that are of presumed organic etiology in Prader-Willi syndrome. Thus, frequent foraging for food and covert consumption continue to be health-threatening problems for many Prader-Willi individuals. This case study was designed to replicate methods for assessment and treatment of food theft. A token program based on differential-reinforcement-of-other-behavior and response-cost eliminated theft in three hospital settings. Prior to discharge, the program was expanded to include contingencies on exercise behavior and weight loss, and staff from the subject's group home residence were trained to implement a modified program in the natural environment. Reduced food theft and continued weight loss were maintained in the group home and an apartment-living arrangement. A total of 81 lb (37 kg) was lost during a 2-yr period. Can Anaesth Soc J. 1983 Sep. No abstract available. Experientia. 1983 Jul 15. No significant difference was found in the range or mean values of ir-beta-endorphin in the plasma of 6 patients with the Prader-Labhart-Willi syndrome compared to 7 of their normal siblings. The hypothesis that some of the symptoms of the P-L-W syndrome are due to excessive opioid activity is not supported by measurement of peripheral levels of ir-beta-endorphin. Exp Clin Endocrinol. 1983 Jul. In two girls (14 and 16 years) and one boy (19 years) with PLW-syndrome and pronounced obesity (240, 210 and 77% overweight) endocrine function tests were carried out. Growth hormone secretion was decreased but normalized after reduction of weight. Thyroxin levels as well as basal and TRH stimulated TSH concentrations were normal. HCG application in the boy induced no rise of the normal basal testosterone levels. Oral glucose tolerance test demonstrated an increased stimulation of insulin in two cases, no other symptoms of diabetes mellitus were found. In the LHRH test an insufficient rise of gonadotropins was found. However, after two weeks of pernasal application of an LHRH analogue (D-Leu6-des-Gly10-EA) the gonadotropin stimulation was distinctly improved and onset of puberty was induced in the male patient. These results are indicative of a hypothalamic disturbance in patients with PLW-syndrome. Horumon To Rinsho. 1983 Jun. No abstract available. Ital J Neurol Sci. 1983 Apr. Identical twins with the Prader-Willi syndrome are reported. Apart from hypogonadism, hypomentia, hypotonia and obesity, they presented shorter than normal stature and the peculiar facies of this syndrome. Both twins also suffered from arterial hypertension with secondary hyperaldosteronism, an abnormality never previously recorded. The endocrinological study showed the presence of hypogonadotrophic hypogonadism in both twins. The GnRH and clomiphene tests suggested a hypothalamic disorder. Although the vast majority of cases with the Prader-Willi syndrome are isolated, the expression of this disorder in two identical twins enhances the possibility of a genetic determination. Am J Ment Defic. 1983 Mar. The physical activity levels of 12 individuals with Prader-Willi syndrome were measured by actometers and pedometers at a 2-week summer camp. Similar measurements were made on 13 nonretarded children at another camp. A wide range of activity levels existed among the Prader-Willi syndrome persons that was greater than that found among the comparison group. Results indicated that it is not valid to stereotype Prader-Willi syndrome individuals when describing their activity levels. Some significant correlations were found between the activity levels of the Prader-Willi syndrome persons and weight loss when age and initial body weight were considered. Can Anaesth Soc J. 1983 Mar. The anaesthetic management of four paediatric patients with the Prader-Willi syndrome is reported. The syndrome is characterized by obesity, mental retardation, genital hypoplasia, hypotonia, and diabetes mellitus. All patients were anaesthetized with halothane. Succinylcholine or pancuronium were used for muscle relaxation, without evidence of abnormal response. Common anaesthetic difficulties in this syndrome are obesity, hypotonia, disturbance in thermoregulation, arrhythmias, diabetes mellitus and convulsions. J Ment Defic Res. 1983 Mar. The results have important heuristic value for several reasons. First, they indicate that contrary to popular belief, individuals with Prader-Willi syndrome do indicate a definite and, in fact, consistent food preference. Further, the degree of food preference seems to be related to the level of cognitive ability. Finally, these subjects consistently chose a lesser amount of preferred food over a greater amount of non-preferred food. This finding has many potential implications for contingent dietary management. These results which are contradictory to many reported observations, also indicate the importance of collecting objective data regarding the eating behaviour of this population. Medicine (Baltimore). 1983 Mar. Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature. An Esp Pediatr. 1983 Jan. Appl Res Ment Retard. 1983. A common behavior problem among Prader-Willi children is inappropriate foraging for food. Theft and subsequent consumption often go undetected and contribute to morbid obesity in many of these individuals. In this study an observational methodology was developed to assess food stealing in two children with Prader-Willi syndrome. The children were observed to steal food at a high rates under baseline conditions in three hospital settings. Subsequent treatment, based on differential reinforcement of other behavior (DRO), consisted of reinforcement of nonstealing at the end of progressively lengthening intervals, and was implemented in multiple baseline fashion across both subjects and settings. Results showed that both subjects' stealing rapidly ceased in treated settings, but failed to show generalization to untreated settings. Follow-up data collected in one setting after termination of active intervention reflected continued nonoccurrence of food stealing, although long-term weight data were not encouraging. Results are discussed in terms of their methodological contribution to the study and treatment of Prader-Willi syndrome. Eur J Pediatr. 1982 Nov. A 7-year-old boy with Prader-Labhart-Willi syndrome who had precocious adrenarche was found to have primary gonadal failure, as evidenced by appropriate laboratory investigations: elevated basal levels of plasma FSH and LH with exaggerated responses to LH-RH stimulation and unresponsiveness of plasma testosterone to repeated hCG stimulations. The elevated values of plasma DHEA which were found indicate an early activation of the adrenal gland. This patient demonstrates the variability of pubertal development in the Prader-Labhart-Willi syndrome, with the unusual association of primary gonadal failure and precocious adrenarche. J Clin Endocrinol Metab. 1982 Sep. Daily plasma melatonin profiles were determined by RIA in exogenously obese and Prader-Willi syndrome children. The melatonin RIA was validated for use in human plasma by evaluating melatonin immunoreactivity in the resultant eluate fractions of a high performance liquid chromatogram of a chloroform-extracted pooled human plasma sample. Melatonin immunoreactivity in the plasma profile occurred only in the fraction that corresponded to the chromatographic position of authentic melatonin. Exogenously obese patients had plasma melatonin profiles characterized by low levels during the day (20-30 pg/ml plasma) and high levels at night (65-130 pg/ml plasma). The plasma melatonin profile did not vary as a function of weight or pubertal status. Prader-Willi syndrome patients had similar melatonin profiles to those of exogenously obese patients. Although the Prader-Willi children had a delayed onset of puberty, the plasma melatonin profile was unaltered. These data indicate that plasma melatonin may not play a role in the onset of puberty. However, the daily melatonin profile is a temporally precise hormonal rhythm in humans. Am J Ophthalmol. 1982 Sep. Nine patients with Prader-Willi syndrome (five female and four male; one Oriental and eight white), all of whom had interstitial deletions of the proximal long arm of one chromosome 15 (q11-q13) were found to have decreased tyrosinase activity in isolated hair bulbs. As infants, all patients had light hair and skin coloring, both of which darkened with age. Light and electron microscopic analysis of skin and hair bulbs disclosed a reduced number of melanocytes in the basal epidermis and hair bulbs. Each patient demonstrated decreased pigmentation of the iris stroma, which was accentuated peripherally and manifested clinically as iris translucency. There was no foveal hypoplasia, nystagmus, or photophobia, and ocular function was normal. Oculocutaneous albinoidism is thus a component of del(15q) Prader-Willi syndrome with reduction of melanocytes of neural crest origin (skin, hair, and iris stroma) and retention of normal retinal and iris pigment epithelia of neuroectodermal origin. Minerva Pediatr. 1982 Feb 28. No abstract available. Am J Ment Defic. 1982 Jan. The relationship between changed or erratic behavior of nine Prader-Willi males and their ingestion of excess kcalories from sucrose was examined. The study was a double-blind design, with objective measures of behavioral change following ingestion of either a sucrose solution or a control preparation containing starch or saccharin. On each of the 3 test days, one of the three test solutions was given, along with a standard 210 kcalorie starch-based breakfast. Blood glucose values at 0.30, 60, 120, and 180 minutes after feeding were compared to the percentage of errors made on paired-associate learning tasks (given eight times daily) and the gross-motor "movement" scores from a wrist monitor and a chair attached to an electrical counter. Results showed that out of 162 test correlations performed, only 8 were significant, exactly the number expected by chance. Possible reasons were suggested as to why no significant differences were found. Masui. 1981 Jul. No abstract available. J Clin Endocrinol Metab. 1981 Jun. Serum pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), insulin and glucose responses to meal stimulation were studied in 10 normal weight patients, 13 normal obese patients and 7 patients with Prader-Willi syndrome (PWS) associated obesity. Serum and plasma concentrations of PP, glucose, insulin and GIP were obtained at 15 min intervals from 0-180 min. after a 275 K calorie meal. Basal and peak responses of glucose, for patients with PWS were significantly lower when compared to normal or obese controls. Basal and peak insulin responses in PWS were significantly greater than those of the normal controls but still less than those of the obese controls. Basal GIP concentrations in the patients with PWS were significantly less than normals and their peak response was less than the obese control group. No significant differences in basal or peak PP responses were noted between normal and obese controls. All 7 patients with PWS had abnormal PP responses. Five failed to show significant PP release after the stimulation; one had a peak response to 130 pg/ml while the 7th patient (PB) had an exaggerated response to 2000 pg/ml. The 6 patients with low or no response had basal PP values of 62 +/- 12 pg/ml and a mean PP peak response of 78 +/- 15 pg/ml. This observation of blunted PP response in a human model of hyperphagia and obesity parallels the animal models and suggests PP may have a significant role in appetite control. Dev Med Child Neurol. 1981 Apr. Of 37 patients with the Prader-Willi syndrome for whom spinal x-rays were available, 32 had a structural scoliosis of 10 degrees or greater. Kyphosis was also found to be more common in older persons with this syndrome, occurring in only one of 14 adolescents but in five of 10 adults. The scoliosis was analyzed in infantile, juvenile, adolescent and adult subgroups. The results suggest that the scoliosis is present from an early age and remains stable during childhood, but progresses in 15 to 20 per cent of cases during adolescence. Scoliosis in patients with Prader-Willi syndrome has many of the clinical characteristics encountered in idiopathic scoliosis. Because it is difficult to detect in these individuals, the authors recommended that baseline spinal X-rays be obtained in all such patients who have suspicious asymmetry of the spine, followed by regular clinical examination, especially during adolescence. Minerva Pediatr. 1981 Mar 15. No abstract available. Klin Padiatr. 1981 Mar. At least in boys hypogenitalism is a constant feature of the Prader-Labhart-Willi Syndrome. Our patient, a 16 10/12 years old girl had the characteristic symptoms of the syndrome and precocious puberty. Menarche had occurred at the age of 8 6/12 years. Precocious puberty does not exclude the diagnosis of a Prader-Labhart-Willi syndrome. J Pediatr Orthop. 1981. Children with Prader-Willi syndrome frequently have musculoskeletal problems such as joint hyperlaxity, hypotonia, delayed bone age, and scoliosis. Their musculoskeletal problems are magnified by the extreme obesity most of these patients exhibit. In certain cases, such as scoliosis, the Prader-Willi patient is placed at significant risk for increased morbidity and mortality. Our paper emphasizes the accurate diagnosis of this syndrome, proper dietary management, and some guidelines regarding surgical evaluation and management of a patient with significant scoliosis. Pediatrics. 1980 Nov. Twenty-seven patients with Prader-Willi syndrome have been described, ten of whom did not receive comprehensive management, nine who were diagnosed and treated after becoming obese, and eight who were diagnosed in infancy and responded to early preventative treatment. Intelligence scores declined in the first two groups, but the group receiving early treatment maintained a mean IQ score 20 points higher than the other two. Even though the underlying mechanism of this disorder remains undefined, a comprehensive early intervention program appears to improve prognosis. Clin Endocrinol (Oxf). 1980 Jan. Hypothalamic, pituitary and gonadal function was studied in five male and three female patients with the Prader-Willi syndrome. All were clinically hypogonadal: all males had low circulating testosterone levels, although in two females basal plasma oestradiol was within the normal range for the early follicular phase of the menstrual cycle. Basal gonadotrophin levels were low and the response to the intravenous ater 10 days and 6 weeks treatment with oral clomiphene (200 mg daily) was followed by a normal rise in luteinizing hormone (LH) and follicle stimulating hormone (FSH) in four out of five patients tested. All five males were tested with human chorionic gonadotrophin (hCG) and the rise in plasma testosterone was subnormonal in four. Treatment with hCG was continued for 6 weeks in these four patients, but in only one did testosterone levels rise (transiently) to the normal adult male range. In one female patient studied no rise in plasma oestradiol was detected in response to human menopausal gonadotrophin (hMG). These results suggest that the hypogonadism in the Prader-Willi syndrome is due to combined hypothalamic and primary gonadal abnormalities. [ 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 | 1999 | 1998 | 1997 | 1996 | 1995 | 1994 | 1993 | 1992 | 1991 | 1990 | 1980-1989 | 1979 and prior ] |