Información del artículo
El síndrome de Prader-Willi (SPW) es un trastorno genético con hallazgos que cambian con la edad. Se caracteriza en la infancia por hipotonía, dificultades para la alimentación, retraso en el desarrollo e hipoplasia genital. En la adolescencia y la edad adulta, la problemática se centra en las alteraciones del comportamiento, la ausencia de saciedad y el retraso mental leve o moderado. En las últimas 2 décadas ha habido progresos remarcables en el conocimiento de sus manifestaciones clínicas y su historia natural, y se han desarrollado tratamientos, como la hormona de crecimiento y los psicofármacos, que han permitido una mejoría de la calidad de vida; sin embargo, los conocimientos acerca de su tratamiento en la edad adulta siguen siendo insuficientes. Este artículo quiere proporcionar una visión global de los problemas clínicos más importantes en el síndrome de Prader-Willi en la edad adulta. Los temas incluidos son la obesidad y sus consecuencias, los factores de riesgo cardiovascular y la diabetes, los problemas respiratorios, los trastornos del sueño, el hipogonadismo, la osteoporosis y los trastornos del comportamiento y psiquiátricos.
Palabras clave:
SPW
Síndrome de Prader-Willi
Edad adulta
Prader-Willi Syndrome (PWS) is a genetic disorder with features that change with age. In infancy, PWS is characterized by hypotonia, feeding difficulties, developmental delay, and genital hypoplasia. In adolescence and adulthood, problems are centered on behavioral disorders, absence of satiety, and mild to moderate mental retardation. In the past two decades remarkable progress has been made in the understanding of its clinical manifestations and natural history, and treatments have been developed, such as growth hormone therapy and the use of psychoactive drugs, which can improve quality of life in these patients. However, knowledge about the management of PWS in adulthood is still poor. This article aims to provide an overall view of the most important clinical problems in adults with PWS. The issues included are obesity and its consequences, cardiovascular risk factors and diabetes, respiratory abnormalities, sleep disorders, hypogonadism, osteoporosis, and behavioral and psychiatric disorders.
Key words:
PWS
Prader-Willi syndrome
Adulthood
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Bibliografía
[1.]
L. Burd, B. Vesely, J. Martsolf, J. Kerbeshian.
Prevalence study of Prader-Willi syndrome in North Dakota.
Am J Med Genet, 37 (1990), pp. 97-99
[2.]
M.G. Butler.
Prader-Willi syndrome: current understanding of cause and diagnosis.
Am J Med Genet, 35 (1990), pp. 319-332
[3.]
A. Prader, A. Labhart, H. Willi.
Ein syndrom von adipositas, kleinwuchs, kryptorchismus und oligophrenie nach myatonieartigem zustand im neugeborenenalter.
Schweiz Med Wschr, 86 (1956), pp. 1260-1261
[4.]
M. Gunay-Aygun, S. Schwartz, S. Heeger, M.A. O’Riordan, S.B. Cassidy.
The changing purpose of Prader-Willi clinical diagnostic criteria and proposed revised criteria.
Pediatrics, 108 (2001), pp. E92
[5.]
D.H. Ledbetter, J.T. Mascarello, V.M. Riccardi, V.D. Harper, S.D. Airhart, R.J. Strobel.
Chromosome 15 abnormalities and the Prader Willi syndrome: a follow up report of 40 cases.
Am J Hum Genet, 34 (1982), pp. 278-285
[6.]
D.H. Ledbetter, V.M. Riccardi, S.D. Airhart, R.J. Strobel, B.S. Keenan, J.D. Crawford.
Deletions of chromosome 15 as a cause of the Prader-Willi syndrome.
N Engl J Med, 304 (1981), pp. 325-329
[7.]
M.G. Butler, C.G. Palmar.
Parenteral origin of chromosome 15 deletion in Prader-Willi syndrome.
Lancet, 1 (1983), pp. 285-286
[8.]
D.F. Swaab.
Prader-Willi syndrome and the hypothalamus.
Acta Paediatr, (1997), pp. 50-54
[9.]
R.D. Nicholls, J.H. Knoll, M.G. Butler, S. Karam, M. Lalande.
Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome.
Nature, 342 (1989), pp. 281-285
[10.]
S.G. Purvis-Smith, T. Saville, S. Manass, M.Y. Yip, P.R. Lam-Po-Tang, B. Duffy, et al.
Uniparental disomy 15 resulting from ‘correction’ of an initial trisomy 15.
Am J Hum Genet, 50 (1992), pp. 1348-1350
[11.]
J.P. Park, J.B. Moeschler, V.H. Hani, A.B. Hawk, D.R. Belloni, W.W. Noll, et al.
Maternal disomy and Prader-Willi syndrome consistent with gamete complementation in a case of familial translocation (3;15)(p25;q11.2).
Am J Med Genet, 78 (1998), pp. 134-139
[12.]
T. Ohta, T.A. Gray, P.K. Rogan, K. Buiting, J.M. Gabriel, S. Saitoh, et al.
Imprinting-mutation mechanisms in Prader-Willy syndrome.
Am J Hum Genet, 64 (1999), pp. 397-413
[13.]
V.A. Holm.
The diagnosis of Prader-Willi syndrome.
The Prader-Willi syndrome, pp. 27-36
[14.]
T. Kubota, J.S. Sutcliffe, S. Adarhya, G. Gillessen-Kaesbach, S.L. Christian, B. Horsthemke, et al.
Validation studies of SNRPN methylation as a diagnostic test for Prader-Willi syndrome.
Am J Med Genet, 66 (1996), pp. 77-80
[15.]
M. Zeschnigk, C. Lich, K. Buiting, W. Doerfler, B. Horsthemke.
A single-tube PCR test for the diagnosis of Angelman and Prader- Willi syndrome based on allelic methylation differences at the SNRPN locus.
Eur J Hum Genet, 4 (1997), pp. 94-98
[16.]
A. Kuwano, A. Mutirangura, B. Dittrich, K. Buiting, B. Horsthemke, S. Saitoh, et al.
Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-q13) by YAC cloning and FISH analysis.
Hum Mol Genet, 1 (1992), pp. 417-425
[17.]
C. Camprubí.
Genética en el síndrome de Prader Willi. Estrategia diagnóstica. Ponencias y comunicaciones.
II Congreso Nacional del Síndrome de Prader-Willi, (2004),
[18.]
B.D. Hall, D.W. Smith.
Prader-Willi syndrome: a resume of 32 cases including an instance of affected first cousins, one of whom is of normal stature and intelligence.
J Pediatr, 81 (1972), pp. 286-293
[19.]
D.J. Creel, C.M. Bendel, G.L. Wiesner, J.D. Wirtschafter, D.C. Arthur, R.A. King.
Abnormalities of the central visual pathways in Prader-Willi syndrome associated with hypopigmentation.
N Engl J Med, 314 (1986), pp. 1606-1609
[20.]
L.R. Greenswag.
Adults with Prader-Willi syndrome: a survey of 232 cases.
Dev Med Child Neurol, 29 (1987), pp. 145-152
[21.]
M.G. Butler, F.J. Meaney.
An anthropometric study of 38 individuals with Prader-Labhart-Willi syndrome.
Am J Med Genet, 26 (1987), pp. 445-455
[22.]
H.M. Hittner, R.A. King, V.M. Riccardi, D.H. Ledbetter, R.P. Borda, R.E. Ferrell, et al.
Oculocutaneous albinoidism as a manifestation of reduced neural crest derivatives in the Prader-Willi syndrome.
Am J Ophtal, 94 (1982), pp. 328-337
[23.]
M.G. Butler.
Hypopigmentation: a common feature of Prader- Labhart-Willi syndrome.
Am J Hum Genet, 45 (1989), pp. 140-146
[24.]
J.B.P. Stephenson.
Prader-Willi syndrome: neonatal presentation and later development.
Dev Med Child Neurol, 22 (1980), pp. 792-795
[25.]
C.T. Schrander-Stumpel, L.M. Curfs, P. Sastrowijoto, S.B. Cassidy, J.J. Schrander, J.P. Fryns.
Prader-Willi syndrome: causes of death in an international series of 27 cases.
Am J Med Genet, 124A (2004), pp. 333-338
[26.]
A. Del Parigi, M. Tschop, M.L. Heiman, A.D. Salbe, B. Vozarova, S.M. Sell, et al.
High circulating grhelin: a potential cause for hyperphagia and obesity in prader-willi syndrome.
J Clin Endocrinol Metab, 87 (2002), pp. 5461-5464
[27.]
N.A. Shapira, M.C. Lessig, A.G. He, G.A. James, D.J. Driscoll, Y. Liu.
Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRL.
J Neurol Neurosurg Psychiatry, 76 (2005), pp. 260-262
[28.]
D.A. Schoeller, L.L. Levitsky, L.L. Bandini, W.W. Dietz, A. Walczak.
Energy expenditure and body composition in Prader-Willi syndrome.
Metabolism, 37 (1988), pp. 115-120
[29.]
P. Brambilla, L. Bosio, P. Manzoni, A. Pietrobelli, L. Beccaria, G. Chiumello.
Peculiar body composition in patients with Prader- Labhart-Willi syndrome.
Am J Clin Nutr, 65 (1997), pp. 1369-1374
[30.]
U. Eiholzer, W.F. Blum, L. Molinari.
Body fat determined by skinfold measurement is elevated despite underweight in infants with Prader-Labhart-Willi syndrome.
J Pediatr, 134 (1999), pp. 222-225
[31.]
P.D.K. Lee, D.M. Wilson, L. Routree, R.L. Hintz, R.G. Rosenfeld.
Linear growth response to exogenous growth hormone in Prader- Willi syndrome.
Am J Med Genet, 28 (1987), pp. 865-867
[32.]
M. Angulo, M. Castro-Magana, B. Mazur, J.A. Canas, P.M. Vitollo, M. Sarrantonio.
Growth hormone secretion and effects of growth hormone therapy on growth velocity and weight gain in children with Prader-Willi syndrome.
J Pediatr Endocrinol Metab, 9 (1996), pp. 393-400
[33.]
A.L. Carrel, S.E. Myers, B.Y. Whitman, D.B. Allen.
Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: a controlled study.
J Pediatr, 134 (1999), pp. 215-221
[34.]
C. Hoybye.
Endocrine and metabolic aspects of adult Prader- Willi syndrome with especial emphasis on the effect of growth hormone treatment.
Growth Horm IGF Res, 14 (2004), pp. 1-15
[35.]
C. Hoybye, M. Thoren, B. Bohm.
Cognitive, emotional, physical and social effects of growth hormone treatment in adults with Prader-Willi syndrome.
J Intellect Diasabil Res, 49 (2005), pp. 245-252
[36.]
C.J. Hoffman, D. Aultman, P. Pipes.
A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes.
J Am Diet Assoc, 92 (1992), pp. 823-830
[37.]
H. Kaufman, G. Overton, J. Leggott, C. Clericuzio.
Prader-Willi syndrome: effect of group home placement on obese patients with diabetes.
South Med J, 88 (1995), pp. 182-184
[38.]
J. Kobayashi, M. Kodama, K. Yamazaki, O. Morikawa, S. Murano, N. Kawamata, et al.
Gastric bypass in a Japanese man with Prader-Willi syndrome and morbid obesity.
Obes Surg, 13 (2003), pp. 803-805
[39.]
P. Burman, E.M. Ritzen, A.C. Lindgren.
Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH.
Endocr Rev, 22 (2001), pp. 787-799
[40.]
J.V. Butler, J.E. Whittington, A.J. Holland, H. Boer, D. Clarke, T. Webb.
Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study.
Dev Med Child Neurol, 44 (2002), pp. 248-255
[41.]
D.P. Schuster, K. Osei, W.B. Zipf.
Characterization of alterations in glucose and insulin metabolism in Prader-Willi subjects.
Metabolism, 45 (1996), pp. 1514-1520
[42.]
H. Kaufman, G. Overton, J. Leggott, C. Clericuzio.
Prader-Willi syndrome: effect of group home placement on obese patients with diabetes.
South Med J, 88 (1995), pp. 182-184
[43.]
R. Bassali, W.H. Hoffman, H. Chen, C.M. Tuck-Muller.
Hyperlipidemia, insulin-dependent diabetes mellitus, and rapidly progressive diabetic retinopathy and nephropathy in Prader-Willi syndrome with del (15) (q11.2q13).
Am J Med Genet, 71 (1997), pp. 267-270
[44.]
A. Vogels, J.P. Fryns.
Age at diagnosis, body mass index and physical morbidity in children and adults with the Prader-Willi syndrome.
Genet Couns, 15 (2004), pp. 397-404
[45.]
A.P. Goldstone, E.L. Thomas, A.E. Brynes, J.D. Bell, G. Frost, N. Saeed, et al.
Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: evidence for novel influences on body fat distribution.
J Clin Endocrinol Metab, 86 (2001), pp. 4330-4338
[46.]
H. Hákonarson, J. Moskovitz, K.L. Daigle, S.B. Cassidy, M.M. Cloutier.
Pulmonary function abnormalities in Prader-Willi syndrome.
J Pediatr, 126 (1995), pp. 565-570
[47.]
W.J. O’Donohue Jr, J.P. Baker, G.M. Bell, O. Muren, C.L. Parker, J.L. Patterson Jr.
Respiratory failure in neuromuscular disease.
JAMA, 235 (1976), pp. 733-736
[48.]
R. Manni, L. Politini, L. Nobili, F. Ferrillo, C. Livieri, E. Veneselli, et al.
Hypersomnia in the Prader Willi syndrome: clinicalelectrophysiological features and underlying factors.
Clin Neurophysiol, 112 (2001), pp. 800-805
[49.]
J. Ren, S. Lee, S. Pagliardini, M. Gerard, C.L. Stewart, J.J. Greer, et al.
Absence of Ndn, encoding the Prader-Willi syndrome-deleted gene necdin, results in congenital deficiency of central respiratory drive in neonatal mice.
J Neurosci, 23 (2003), pp. 1569-1573
[50.]
S. Clift, M. Dahlitz, J.D. Parkes.
Sleep apnoea in the Prader-Willi syndrome.
J Sleep Res, 3 (1994), pp. 121-126
[51.]
I.E. Smith, M.A. King, P.W. Siklos, J.M. Shneerson.
Treatment of ventilatory failure in the Prader-Willi syndrome.
Eur Respir J, 11 (1998), pp. 1150-1152
[52.]
R.H. Wharton, T. Wang, F. Graeme-Cook, S. Briggs, R.E. Cole.
Acute idiopathic gastric dilatation with gastric necrosis in individuals with Prader-Willi syndrome.
Am J Med Genet, 73 (1997), pp. 437-441
[53.]
G.A. Bray, W.T. Dahms, R.S. Swerdloff, R.H. Fiser, R.L. Atkinson, R.E. Carrel.
The Prader-Willi syndrome: a study of 40 patients and a review of the literature.
Medicine (Baltimore), 62 (1983), pp. 59-80
[54.]
B. Garty, A. Shuper, M. Mimouni, I. Varsano, R. Kauli.
Primary gonadal failure and precocious adrenarche in a boy with Prader- Labhart-Willi syndrome.
Eur J Pediatr, 139 (1982), pp. 201-203
[55.]
A. Crino, R. Schiaffini, P. Ciampalini, S. Spera, L. Beccaria, F. Benzi, et al.
Hypogonadism and pubertal development in Prader- Willi syndrome.
Eur J Pediatr, 162 (2003), pp. 327-333
[56.]
R. Kauli, R. Prager-Lewin, Z. Laron.
Pubertal development in the Prader-Labhart-Willi syndrome.
Acta Paediatr Scand, 67 (1978), pp. 763-767
[57.]
A. Akefeldt, C.J. Tornhage, C. Gillberg.
A woman with Prader- Willi syndrome gives birth to a healthy baby girl.
Dev Med Child Neurol, 41 (1999), pp. 789-790
[58.]
A. Schulze, H. Mogensen, B. Hamborg-Petersen, N. Graem, J.R. Ostergaard, K. Brondum-Nielsen.
Fertility in Prader-Willi syndrome: a case report with Angelman syndrome in the offspring.
Acta Paediatr, 90 (2001), pp. 455-459
[59.]
U. Eiholzer, K. Stutz, C. Weinmann, T. Torresani, L. Molinari, A. Prader.
Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome.
Eur J Pediatr, 157 (1998), pp. 890-893
[60.]
A. Corrias, J. Bellone, L. Beccaria, L. Bosio, G. Trifiro, C. Livieri, et al.
GH/IGF-I axis in Prader-Willi syndrome: evaluation of IGF-I levels and of the somatotroph responsiveness to various provocative stimuli. Genetic Obesity Study Group of Italian Society of Pediatric Endocrinology and Diabetology.
J Endocrinol Invest, 23 (2000), pp. 84-89
[61.]
Generalitat de Catalunya. Criteris d’indicació i seguiment del tractament amb hormona de creixement [citado el 20 de septiembre de 2005]. Disponible en: http://www.gencat.net/salut/depsan/units/sanitat/pdf/cautnex2004.pdf
[62.]
C. Hoybye, J. Frystyk, M. Thoren.
The growth hormone-insulinlike growth factor axis in adult patients with Prader Willi syndrome.
Growth Horm IGF Res, 13 (2003), pp. 269-274
[63.]
S.B. Cassidy, J.A. McKillop.
Temperature regulation in Prader-Willi syndrome.
Am J Med Genet, 41 (1991), pp. 528
[64.]
M.S. Wise, H. Zohbi, M. Edwards, L.K. Byrd, A.E. Guttmacher, F. Greenberg.
Hyperthermia in infants with Prader-Willi syndrome.
Am J Med Genet, 42 (1992), pp. 262-263
[65.]
K. Rubin, S.B. Cassidy.
Hypogonadism and osteoporosis.
Management of Prader- Willi syndrome, pp. 23-33
[66.]
P.S. Hart.
Salivary abnormalities in Prader-Willi syndrome.
Ann N Y Acad Sci, 842 (1998), pp. 125-131
[67.]
N.O. Salako, H.M. Ghafouri.
Oral findings in a child with Prader- Labhart-Willi syndrome.
Quintessence Int, 26 (1995), pp. 339-341
[68.]
W.L. Robson, V. Shashi, S. Nagaraj, J.P. Norgaard.
Water intoxication in a patient with the Prader-Willi syndrome treated with desmopressin for nocturnal enuresis.
J Urol, 157 (1997), pp. 646-647
[69.]
F.J. Symons, M.G. Butler, M.D. Sanders, I.D. Feurer, T. Thompson.
Self-injurious behaviour and Prader-Willi syndrome: behavioral forms and body locations.
Am J Ment Retard, 104 (1999), pp. 260-269
[70.]
F. Campeotto, C. Naudin, G. Viot, C. Dupont.
Automutilation rectale, rectorragies et syndrome de Prader-Willi.
Arch Pediatr, 8 (2001), pp. 1075-1077
[71.]
J. Whittington, A. Holland, T. Webb, J. Butler, D. Clarke, H. Boer.
Academic underachievement by people with Prader-Willi syndrome.
J Intellect Disabil, 48 (2004), pp. 188-200
[72.]
E.M. Dykens, B. Shah.
Psychiatric disorders in Prader-Willi syndrome: epidemiology and management.
CNS Drugs, 17 (2003), pp. 167-178
[73.]
S.L. Einfeld, A. Smith, S. Durvasula, T. Florio, B.J. Tonge.
Behavior and emotional disturbances in Prader-Willi syndrome.
Am J Med Genet, 82 (1999), pp. 123-127
[74.]
E.M. Dykens, J.F. Leckman, S.B. Cassidy.
Obsessions and compulsions in Prader-Willi syndrome.
J Child Psychol Psychiatry, 37 (1996), pp. 995-1002
[75.]
M. State, E.M. Dykens, B. Rosner, A. Martin, B.H. King.
Obsessive- compulsive symptoms in Prader-Willi and “Prader-Willi-Like” patients.
J Am Acad Child Adolesc Psychyatry, 38 (1999), pp. 329-334
[76.]
D.J. Clarke, H. Boer, J. Whittington, A. Holland, J. Butler, T. Webb.
Prader-Willi syndrome, compulsive and ritualistic behaviours: the first population-based survey.
Br J Psychiatry, 180 (2002), pp. 358-362
[77.]
W.M.A. Verhoeven, L.M.G. Curfs, S. Tuinier.
Prader-Willi syndrome and cycloid psychosis.
J Intellect Disabil Res, 42 (1998), pp. 455-462
[78.]
M.J. Descheemaeker, A. Vogels, V. Govers, M. Borghgraef, D. Willekens, A. Swillen, et al.
Prader-Willi syndrome: new insight in the behavioural and psychiatric spectrum.
J Intellect Disabil Res, 46 (2002), pp. 41-50
[79.]
A. Vogels, M. De Hert, M.J. Descheemaeker, V. Govers, K. Devriendt, E. Legius, et al.
Psychotic disorders in Prader Willi syndrome.
Am J Med Genet, 127 (2004), pp. 238-243
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