RESUMEN
Prader-Willi syndrome (PWS) is the most common genetic syndrome with obesity and results from loss of expression of paternally inherited genes on chromosome 15q11-q13 by a variety of mechanisms which include large deletions (70%-75%), maternal uniparental disomy (UPD) (20%-30%), and imprinting defects (2%-5%) or balanced translocations. Individuals often have a characteristic behavior disorder with mild intellectual disability, infantile hypotonia associated with poor sucking, short stature, and obesity. PWS is characterized by hypothalamic-pituitary axis dysfunction with growth hormone (GH) deficiency, hypogonadism, and several other hormonal deficiencies resulting in short stature, centrally driven excessive appetite (hyperphagia), central obesity, cryptorchidism, and decreased lean body mass. In this study, we determined and sought differences in the incidence of thyroid abnormalities among the common genetic subtypes in a cohort of 52 subjects with PWS because there was limited literature available. We also sought the effects of growth hormone (GH) treatment on the thyroid profile. Fifty-two subjects with a genetically confirmed diagnosis of PWS were included in this study at the University of California, Irvine. Blood samples for baseline thyroxine stimulating hormone (TSH) and free thyroxine (fT4) levels were obtained in the morning after an overnight fast for 8-12 h. Statistical analyses were performed with SPSS (SPSS Inc., 21.0). Mean values were analyzed by one-way ANOVA, and student's t-test and statistical significance were set at p < 0.05. The subjects included 26 males and 26 females with an age range of 3-38 years. There were 29 subjects with chromosome 15q11-q13 deletions and 23 with UPD; 28 were GH treated currently or in the past, and 24 never received GH. There was no significant difference in age or body mass index (BMI) (kg/m2) between GH-treated versus non-GH-treated groups. BMI was higher in the deletion group compared to the UPD group (p = 0.05). We identified two individuals who were clinically diagnosed and treated for hypothyroidism, one of whom was on GH supplements. We identified two additional individuals with subclinical hypothyroidism who were not on GH treatment, giving a frequency of 7.6% (4/52) in this cohort of patients. We did not find significant differences in thyroid function (TSH) in the deletion versus UPD groups. We found significant differences in thyroid function, however, between GH-treated and non-GH-treated groups. The mean TSH was lower (2.25 ± 1.17 uIU/M, range 0.03-4.92 uIU/M versus 2.80 ± 1.44 uIU/M, range 0.55-5.33 uIU/M respectively, p = 0.046), and the free T4 levels were significantly higher (1.13 ± 0.70 and 1.03 ± 0.11 ng/dL, respectively, p = 0.05) in the GH-treated individuals compared to non-GH-treated individuals. In this cohort of subjects with PWS, we identified two previously diagnosed individuals with hypothyroidism and two individuals with subclinical hypothyroidism (4/52, 7.6%), three of whom were not receiving GH treatment. We did not find any significant differences in thyroid function between molecular subtypes; however, we found that euthyroid status (lower TSH levels and higher free T4 levels) was significantly higher in individuals who were treated with GH compared to the untreated group. We recommend that individuals with PWS should be screened regularly for thyroid deficiency and start treatment early with GH in view of the potentially lower incidence of thyroid deficiency.
RESUMEN
Prader-Willi syndrome (PWS) affects 1/15,000-1/30,000 live births and is characterized by lack of expression of paternally inherited genes on 15q11.2-15q13 caused by paternal deletions, maternal uniparental disomy (UPD), or imprinting defects. Affected individuals have distinct physical features, and growth hormone (GH) deficiency occurs in some individuals with PWS. The aim of this study is to test the hypotheses that (a) individuals with deletions and UPD have different physical and dysmorphic features, (b) individuals treated with GH have different physical and dysmorphic features than those not treated, and (c) GH treatment effects are different for individuals with UPD in comparison to those with deletions. Study participants included 30 individuals with deletions or UPD, who did or did not have GH treatment. Participants' molecular abnormalities were determined by molecular and cytogenetic analysis. Clinical data were obtained by a single dysmorphologist. Individuals with deletions were found to be heavier (p = .001), taller (p = .031), with smaller head circumferences (p = .042) and were more likely to have fair skin and hair than their family members (p = .031, .049, respectively) compared to UPD patients. Females with deletions more commonly had hypoplastic labia minora (p = .009) and clitoris (.030) in comparison to those with UPD. Individuals who received GH in both deletion and UPD groups were taller (p = .004), had larger hands (p = .011) and feet (p = .006) and a trend for a larger head circumference (p = .103). Interestingly, the GH-treated group also had a lower rate of strabismus (esotropia [p = .017] and exotropia [p = .039]). This study showed statistically significant correlations between phenotype and molecular subtypes and also between phenotype and GH treatment.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 15/genética , Hormona del Crecimiento/genética , Síndrome de Prader-Willi/genética , Adolescente , Estatura/genética , Niño , Preescolar , Análisis Citogenético/métodos , Exotropía/genética , Exotropía/patología , Femenino , Impresión Genómica/efectos de los fármacos , Hormona del Crecimiento/administración & dosificación , Humanos , Masculino , Fenotipo , Síndrome de Prader-Willi/clasificación , Síndrome de Prader-Willi/tratamiento farmacológico , Síndrome de Prader-Willi/patología , Disomía Uniparental/genética , Disomía Uniparental/patologíaRESUMEN
Prader-Willi syndrome (PWS) is a genomic imprinting disorder characterized by infantile hypotonia with a poor suck and failure to thrive, hypogenitalism/hypogonadism, behavior and cognitive problems, hormone deficiencies, hyperphagia, and obesity. The Stanford Binet and Wechsler (WAIS-R; WISC-III) intelligence (IQ) tests were administered on 103 individuals with PWS from two separate cohorts [University of California, Irvine (UCI) (N = 56) and Vanderbilt University (N = 47)] and clinical information obtained including growth hormone (GH) treatment, PWS molecular classes, weight and height. Significantly higher IQ scores (p < .02) were found representing the vocabulary section of the Stanford Binet test in the growth hormone (GH) treated group when compared with non-GH treatment in the pediatric-based UCI PWS cohort with a trend for stabilization of vocabulary IQ scores with age in the GH treated maternal disomy (UPD) 15 subject group. Significant differences (p = .05) were also found in the adult-based Vanderbilt PWS cohort with 15q11-q13 deletion subjects having lower Verbal IQ scores compared with UPD 15. No difference in body mass index was identified based on the PWS molecular class or genetic subtype. Medical care and response to treatment with growth hormone may influence intelligence impacted by PWS genetic subtypes and possibly age, but more studies are needed.
Asunto(s)
Cromosomas Humanos Par 15/genética , Hormona del Crecimiento/administración & dosificación , Síndrome de Prader-Willi/tratamiento farmacológico , Eliminación de Secuencia/genética , Adolescente , Adulto , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Inteligencia/efectos de los fármacos , Pruebas de Inteligencia , Masculino , Fenotipo , Síndrome de Prader-Willi/clasificación , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patología , Prueba de Stanford-Binet , Escalas de Wechsler , Adulto JovenAsunto(s)
Hormona de Crecimiento Humana , Síndrome de Prader-Willi , Humanos , Obesidad , Prevalencia , Adulto JovenRESUMEN
Prader-Willi syndrome (PWS) is caused by a deficiency of imprinted genes in the 15q11-q13 region and is characterized by prenatal onset of hypotonia, poor feeding, childhood-onset obesity, hyperphagia, short stature, facial dysmorphism, intellectual disability, and behavioral problems. We studied perinatal factors in a cohort of 64 people with PWS resulting from paternal deletion of 15q11-q13 and maternal uniparental disomy (UPD) for chromosome 15. We recruited 34 individuals with deletion and 30 with UPD. We compared the frequency of multiple prenatal and neonatal factors with the general population as well as between the two genetic subtypes. Of the 64 individuals with PWS, fetal movements were decreased in 82.8%, 31.7% were born prematurely, 42.1% by Cesarean section, and 35.9% required oxytocin induction. Apgar scores were low in 34.6%, 96.8% had feeding difficulty, 50% needed tube feeding, and 6.2% subsequently had gastrostomy tube placement. On comparing findings in the deletion versus the UPD groups, we did not find many significant differences. We, however, found a higher maternal age, and also later age at diagnosis in the UPD versus the deletion group. PWS subjects have higher rates of perinatal complications, especially Cesarean section rate, hypotonia, and low Apgar scores compared to the general population. We did not find many differences between the genetic subtypes, except for later age of diagnosis of the UPD 15 group suggesting a milder phenotype. We also found that the mothers in the UPD were older, supporting the hypothesis that UPD results from nondisjunction associated trisomy rescue.
Asunto(s)
Deleción Cromosómica , Exposición Materna/efectos adversos , Síndrome de Prader-Willi/etiología , Disomía Uniparental/genética , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Fenotipo , Síndrome de Prader-Willi/diagnóstico , Embarazo , Complicaciones del Embarazo , Factores de RiesgoRESUMEN
Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype. Sleep abnormalities and scoliosis are common. Growth hormone insufficiency is frequent, and replacement therapy provides improvement in growth, body composition, and physical attributes. Management is otherwise largely supportive. Consensus clinical diagnostic criteria exist, but diagnosis should be confirmed through genetic testing. Prader-Willi syndrome is due to absence of paternally expressed imprinted genes at 15q11.2-q13 through paternal deletion of this region (65-75% of individuals), maternal uniparental disomy 15 (20-30%), or an imprinting defect (1-3%). Parent-specific DNA methylation analysis will detect >99% of individuals. However, additional genetic studies are necessary to identify the molecular class. There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. Sibling recurrence risk is typically <1%, but higher risks may pertain in certain cases. Prenatal diagnosis is available.
Asunto(s)
Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Diagnóstico Diferencial , Estudios de Asociación Genética , Asesoramiento Genético , Pruebas Genéticas , Humanos , Morbilidad , Síndrome de Prader-Willi/epidemiología , Síndrome de Prader-Willi/terapiaRESUMEN
An international group of clinicians working in the field of dysmorphology has initiated the standardization of terms used to describe human morphology. The goals are to standardize these terms and reach consensus regarding their definitions. In this way, we will increase the utility of descriptions of the human phenotype and facilitate reliable comparisons of findings among patients. Discussions with other workers in dysmorphology and related fields, such as developmental biology and molecular genetics, will become more precise. Here we introduce the anatomy of the periorbital area and define and illustrate the terms that describe the major characteristics of the periorbital area.
Asunto(s)
Órbita/anatomía & histología , Terminología como Asunto , Cejas/anomalías , Cejas/anatomía & histología , Cejas/patología , Pestañas/anomalías , Pestañas/anatomía & histología , Pestañas/patología , Párpados/anomalías , Párpados/anatomía & histología , Párpados/patología , Femenino , Humanos , Aparato Lagrimal/anomalías , Aparato Lagrimal/anatomía & histología , Aparato Lagrimal/patología , Masculino , Órbita/anomalías , Órbita/patología , FenotipoRESUMEN
Prader-Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2-q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect.
Asunto(s)
Síndrome de Prader-Willi , Adolescente , Adulto , Niño , Trastornos de la Conducta Infantil/genética , Trastornos de la Conducta Infantil/terapia , Preescolar , Cromosomas Humanos Par 15/genética , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/terapia , Femenino , Asesoramiento Genético , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipogonadismo/terapia , Lactante , Masculino , Hipotonía Muscular/genética , Hipotonía Muscular/terapia , Obesidad/genética , Obesidad/terapia , Fenotipo , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/fisiopatología , Síndrome de Prader-Willi/terapia , Trastornos Psicóticos/genética , Trastornos Psicóticos/terapia , Adulto JovenRESUMEN
Hyperphagia and obesity are common features in individuals with Prader-Willi syndrome (PWS). Demographic and cause-of-death data from individuals with PWS were obtained through a national support organization. Four reports of unexpected mortality due to gastric rupture and necrosis were found in 152 reported deaths, accounting for 3% of the causes of mortality. Four additional individuals were suspected to have gastric rupture. Vomiting and abdominal pain, although rare in PWS, were frequent findings in this cohort. The physician should consider an emergent evaluation for gastric rupture and necrosis in individuals with PWS who present with vomiting and abdominal pain.
Asunto(s)
Necrosis/diagnóstico , Síndrome de Prader-Willi/complicaciones , Rotura Gástrica/diagnóstico , Dolor Abdominal/etiología , Adolescente , Adulto , Causas de Muerte , Niño , Femenino , Dilatación Gástrica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Necrosis/mortalidad , Necrosis/patología , Rotura Gástrica/mortalidad , Rotura Gástrica/patología , Vómitos/etiologíaRESUMEN
OBJECTIVE: Cryptic subtelomeric chromosome rearrangements account for 6% to 10% of idiopathic mental retardation. As cytogenetic and molecular techniques have become more sophisticated, the number of genetic syndromes attributed to these microdeletions has increased. To date, 64 patients have been described in the literature with a more recently recognized microdeletion syndrome, del 22q13.3. The purpose of this study is to present 11 new cases of this recently described syndrome to delineate further the phenotype and to alert the clinician to another genetic condition that should be considered in the differential diagnosis of early hypotonia, delayed speech acquisition, and autistic behavior. METHODS: Eleven patients were evaluated in 3 academic institutions. Clinical features and results of cytogenetic testing were recorded and tabulated. Reasons for referral for genetic evaluation included developmental delay, severe expressive speech and language delay, and dysmorphic features. RESULTS: Age of presentation ranged from 5 months to 46 years. There were 10 female patients and 1 male patient. All of the patients exhibited delayed motor development, some degree of hypotonia, and severe expressive speech and language delay. Dysmorphic facial features included epicanthal folds, large cupped ears, underdeveloped philtrum, loss of cupid's bow, and full supraorbital ridges. Six patients exhibited autistic-like behaviors. Microscopically visible chromosome deletions were observed in 6 patients. In the remainder, the deletion was detected with the use of fluorescence in situ hybridization. CONCLUSIONS: Hypotonia and developmental delay are nonspecific findings observed in many malformation and genetic syndromes. However, in association with severe speech and language delay and autistic-like behavior, this phenotype may be a significant indication to consider the 22q13 deletion syndrome as a potential cause.
Asunto(s)
Trastorno Autístico/genética , Deleción Cromosómica , Cromosomas Humanos Par 22 , Cara/anomalías , Trastornos del Lenguaje/genética , Trastornos del Habla/genética , Anomalías Múltiples/genética , Niño , Preescolar , Análisis Citogenético , Discapacidades del Desarrollo/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana EdadRESUMEN
Fragile X syndrome is an X-linked disorder characterized primarily by speech delay and moderate mental retardation. The incidence of fragile X syndrome is estimated at 1/4000-1/6000 males and half that for females. This article presents a case study of fragile X syndrome, describing the genetics and inheritance, disease characteristics,natural history, diagnosis, differential diagnosis, and management.
Asunto(s)
Discapacidades del Desarrollo/genética , Síndrome del Cromosoma X Frágil , Discapacidad Intelectual/genética , Preescolar , Discapacidades del Desarrollo/diagnóstico , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/terapia , Humanos , Discapacidad Intelectual/diagnóstico , Masculino , Atención Primaria de SaludRESUMEN
PURPOSE: The purpose of this study was to test the hypothesis that deletions of varying sizes in de novo apparently balanced chromosome rearrangements are a significant cause of phenotypic abnormalities. METHODS: A total of fifteen patients, with seemingly balanced de novo rearrangements by routine cytogenetic analysis but with phenotypic anomalies, were systematically analyzed. We characterized the breakpoints in these fifteen cases (two of which were ascertained prenatally), using a combination of high-resolution GTG-banding, fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BACs), and data from the Human Genome Project. RESULTS: Molecular cytogenetic characterization of the 15 patients revealed nine with deletions, ranging in size from 0.8 to 15.3 Mb, with the number of genes lost ranging from 15 to 70. In five of the other six cases, a known or putative gene(s) was potentially disrupted as a result of the chromosomal rearrangement. In the remaining case, no deletions were detected, and no known genes were apparently disrupted. CONCLUSIONS: Our study suggests that the use of molecular cytogenetic techniques is a highly effective way of systematically delineating chromosomal breakpoints, and that the presence of deletions of varying size is an important cause of phenotypic abnormalities in patients with "balanced" de novo rearrangements.
Asunto(s)
Eliminación de Gen , Reordenamiento Génico/genética , Fenotipo , Bandeo Cromosómico , Cromosomas Artificiales Bacterianos , Cromosomas Humanos X/genética , Análisis Citogenético , Femenino , Reordenamiento Génico/fisiología , Proyecto Genoma Humano , Humanos , Hibridación Fluorescente in Situ , Masculino , Espectrofotometría UltravioletaRESUMEN
There is an assumption of parsimony with regard to the number of chromosomes involved in rearrangements and to the number of breaks within those chromosomes. Highly complex chromosome rearrangements are thought to be relatively rare, with the risk for phenotypic abnormalities increasing as the number of chromosomes and chromosomal breaks involved in the rearrangement increases. We report here five cases of de novo complex chromosome rearrangements, each with a minimum of four breaks. Deletions were found in four cases, and in at least one case, a number of genes or potential genes might have been disrupted. This study highlights the importance of the detailed delineation of complex rearrangements, beginning with high-resolution chromosome analysis, and emphasizes the utility of fluorescence in situ hybridization in combination with the data available from the Human Genome Project as a means to delineate such rearrangements.
Asunto(s)
Anomalías Múltiples/genética , Aberraciones Cromosómicas , Trastornos de los Cromosomas/genética , Reordenamiento Génico/genética , Adulto , Línea Celular , Preescolar , Bandeo Cromosómico , Cromosomas Artificiales Bacterianos , Cósmidos , Femenino , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Cariotipificación , MasculinoRESUMEN
Prader-Willi syndrome (PWS) is a complex condition with many medical and psychological features. In individuals with this syndrome, causes of death were studied. Data of 27 case reports were collected. Ages at death ranged from neonatal to 68 years. None of the individuals were treated with growth hormone (GH). Most cases were not completely documented and autopsy was performed in a minority of cases only. In five cases, death was considered not to be causally related to PWS. Hypotonia with hypoventilation was noted in the babies, and acute respiratory illness with unexpected sudden death was experienced in young children with PWS. Two young children died after a short period of fever and gastroenteritis. Obesity and its complications leading to death were pronounced in the adult group. One (possibly two) adult(s) died from gastric dilatation and shock. Based on these data, some cautious conclusions can be drawn. In babies with PWS hypoventilation is a risk factor; upper airway infection may be more serious than anticipated and any other clinical features pointing to an infection should be taken very seriously. Therefore, young infants with PWS hospitalized with an upper airway infection and/or hypoventilation or gastroenteritis symptoms, should be closely monitored. Early diagnosis and prevention of overweight is a major factor in preventing early causes of death in individuals with PWS. In the adult group, weight reduction is important but difficult to manage. Sleep apnea should be recognized and treated. Pain in the upper stomach and/or vomiting should be taken as a possible sign of acute intestinal dilatation; intravenous support may be life saving.
Asunto(s)
Síndrome de Prader-Willi/mortalidad , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Dilatación Gástrica/complicaciones , Humanos , Lactante , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/prevención & control , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/prevención & control , Estudios Prospectivos , Síndromes de la Apnea del Sueño/complicacionesRESUMEN
The important role of genetics in pediatric illness has been increasingly recognized, but the true impact has not been well delineated. An important study of pediatric inpatient admissions to a children's hospital in 1978 found a genetic basis for disease in just less than half of admitted patients. We sought to update this study in light of current hospitalization practices and new knowledge about genetics. We systematically reviewed the records of 5,747 consecutive admissions (4,224 individuals), representing 98% of patients admitted in 1996 to Rainbow Babies and Children's Hospital (Cleveland, OH). Each patient was assigned to one of five groups on the basis of the presence or absence of an underlying chronic medical condition and whether that condition had a genetic basis or susceptibility. An underlying disorder with a significant genetic component was found in 71% of admitted children. The vast majority (96%) of underlying chronic disorders in children in this study were either clearly genetic or had a genetic susceptibility. Total charges for 1996 were >$62 million, of which $50 million (81%) was accounted for by disorders with a genetic determinant. The 34% of admissions with clearly genetic underlying disorders accounted for 50% (>$31 million) of the total hospital charges. The mean length of stay was 40% longer for individuals with an underlying disease with a genetic basis than for those with no underlying disease. Charges and length of stay were similar for children with underlying chronic disorders, regardless of the cause. This study begins to quantify the enormous impact of genetic disease on inpatient pediatrics and the health care system. Additional study and frank public discourse are needed to understand the implications on the future health care workforce and on the utilization of health care resources.
Asunto(s)
Costo de Enfermedad , Enfermedades Genéticas Congénitas/economía , Hospitales Pediátricos/economía , Niño , Preescolar , Enfermedades Genéticas Congénitas/epidemiología , Humanos , Recién Nacido , Tiempo de Internación/economía , Estados UnidosRESUMEN
OBJECTIVE: To evaluate the frequency of cancers recorded by the Surveillance, Epidemiology, and End Results (SEER) Program in persons with Prader-Willi syndrome (PWS) METHODS: A survey was mailed in 1994 to 1852 registrants of the PWS Association (USA) inquiring about a diagnosis of any type of benign tumor or cancer (malignant tumor or leukemia). The risk of developing cancer was then estimated by comparing the observed number of cancers in the PWS population during 1975 to 1994 to the expected number in the general US population using data from the 1971-1994 SEER Cancer Statistics Review. RESULTS: Of the 1852 persons, 1160 (63%) responded, or 75% (1160/1552) of those who received the survey. The total number of observed cancer cases in the PWS study population was 8 versus 4.80 expected in the general US population (P =.1610). Three cases of myeloid leukemia were observed versus 0.075 leukemias expected (P =.0001). CONCLUSIONS: There appears to be an increased risk of myeloid leukemias, but not other cancers, among persons with PWS.
Asunto(s)
Leucemia Mieloide/epidemiología , Leucemia Mieloide/etiología , Síndrome de Prader-Willi/complicaciones , Adolescente , Adulto , Sesgo , Causas de Muerte , Niño , Deleción Cromosómica , Cromosomas Humanos Par 15 , Femenino , Encuestas Epidemiológicas , Humanos , Leucemia Mieloide/diagnóstico , Masculino , Neoplasias/epidemiología , Neoplasias/etiología , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/mortalidad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Programa de VERF , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
A behavioral phenotype is the characteristic cognitive, personality, behavioral, and psychiatric pattern that typifies a disorder. A number of genetic syndromes have been identified as having this type of distinctive and consistent behavior pattern. It may act as an important diagnostic sign, like a malformation or characteristic facial appearance. Such patterns are also useful for the physician's anticipatory guidance from an educational, rehabilitative, and parenting perspective. In addition, because they are the consequences of known genetic alterations, behavioral phenotypes can be potentially highly valuable clues to the identification of genes in the population that are important to determination of cognitive skills or deficits, personality determinants, behavioral abnormalities, or psychiatric disorders. The nature of a behavioral phenotype and its potential for genetic insight can be appreciated through the examples of Williams syndrome, Prader-Willi syndrome, and Angelman syndrome. The cognitive and behavioral characteristics of these disorders are distinctive. Williams syndrome is known for its association with remarkable conversational verbal abilities and excessive empathy, whereas Prader-Willi syndrome is known for temper tantrums and obsessive-compulsive features, and Angelman syndrome is associated with a constantly happy affect and hyperactivity. The genetic basis for each of these disorders is known, and the pathophysiology and genotype-phenotype correlations are beginning to provide insight into genes responsible for personality characteristics and behavioral abnormalities.