[Medical and behavioural aspects of Angelman syndrome]. / Aspectos médicos y conductuales del síndrome de Angelman.

INTRODUCTION: Angelman syndrome (AS) is a genetically-based disorder that is characterised by a physical and behavioural phenotype. Additionally, it presents a number of different systemic conditions that must also be taken into account. To evaluate the symptomatic spectrum of AS, we sought the aid of families linked to AS associations by sending them a questionnaire designed to investigate the clinical characteristics of AS. PATIENTS AND METHODS: The families were sent a questionnaire aimed at determining the medical and behavioural characteristics of AS. Results from 68 patients were analysed. RESULTS: The mean age at diagnosis was 4.8 years. The first symptoms that called parents' attention were feeding problems, followed by gastroesophageal reflux and hypotonia. The mean age at which patients were capable of maintaining a sitting posture was 18 months, while autonomous walking was not achieved until 43 months. Epilepsy, which was present in 91% of cases, began with febrile seizures in 55% of patients. In this study we found that a high percentage of patients with AS have a high resistance to pain (67%), a very common symptom in Prader-Willi syndrome, but little known in AS. CONCLUSIONS: This study offers a wide array of information about the clinical spectrum of AS obtained from an extensive populational sample. Some highly prevalent clinical aspects, such as the relative insensitivity to pain, have not been reported in previous publications as a symptom that is typical of AS.

[Behavioural phenotypes in genetic mental retardation]. / Fenotipos conductuales en el retraso mental de origen genetico.

INTRODUCTION: Based on clinical and genetic knowledge about certain syndromes, in recent decades the concept of behavioural phenotypes has been developed in an attempt to deal with the complex relations between genes and behaviour. The model is not linear but rather each type of behaviour is determined by the interaction of different genes and modulated by environmental factors. DEVELOPMENT AND CONCLUSIONS: The aim of this review is to provide a global view concerning the concept of 'behavioural phenotypes' based on the description of the molecular mechanisms and clinical observations of some syndromes. There is clearly a need for geneticists, who work in a laboratory, and clinicians, who can offer qualitative and quantitative data about behaviour in certain genetic syndromes, to work in collaboration. For this reason this study describes the clinical instruments that make it possible to evaluate the core aspects of behaviour and hence undertake their scientific study in situations in which their genetic dysfunction is already known.

[Chromosomal causes that produce mental retardation: chromosome disorders that can be diagnosed in the patient]. / Causas cromosomicas que originan el retraso mental: alteraciones cromosomicas diagnosticables en el paciente.

INTRODUCTION: In all the aetiological studies carried out on idiopathic mental retardation (MR), chromosomal abnormalities are the factor that makes the most significant contribution. The alterations are more frequent when severe MR is accompanied by a dysmorphic phenotype, but can also be found in subjects with mild MR and with few signs of dysmorphism. DEVELOPMENT: This work reports on new genes and critical regions in syndromes with microdeletion, such as Wolf-Hirschhorn, Smith-Magenis and Sotos--which must be taken into account in the genetic diagnosis--and new microduplications like 15q11-q13, which is associated to a behavioural phenotype of autism. The application of new molecular techniques, such as fluorescent in situ hybridisation (FISH) with multiple telomere probes, MLPA (multiplex ligation-dependent probe amplification) and array-CGH (microarray based on compared genomic hybridisation), have shown the important role played by subtelomeric and interstitial rearrangements in the aetiology of MR. Subtelomeric alterations contribute to between 5 and 7% of cases of idiopathic MR, the higher proportion corresponding to deletions, one of the most common of which is deletion 1p36. Studies that evaluate the global genome in idiopathic MR detect from 7% to 20% of cases with anomalies, the interstitial type being more frequent than the subtelomeric kind. CONCLUSIONS: The application of new technologies to idiopathic MR opens up a promising new field for the diagnosis of new syndromes with submicroscopic alterations, so that a prognosis can be determined, treatment can be improved and the risk of relapse can be defined.

[From the clinical to the genetic diagnosis of Prader-Willi and Angelman syndromes]. / Del diagnóstico clínico al diagnóstico genético de los síndromes de Prader-Willi y Angelman.

INTRODUCTION AND DEVELOPMENT: Angelman syndrome (AS) is characterised by severe mental retardation (MR), the absence of language, ataxia and/or tremors in the extremities and a characteristic behavioural phenotype with a happy behaviour and hyperactivity. Patients often show signs of microcephaly and convulsions. Prader-Willi syndrome (PWS) is characterised by acute hypotonia and feeding problems in the neonatal period, and triggers an uncontrollable appetite in the infant that leads to obesity. Most patients have some degree of MR, behavioural disorders and hypogonadism. Both pathologies are caused by a number of genetic mechanisms that affect the 15q11-q13 region regulated by genomic imprinting, which means that only one of the two copies of the genes in this region will be functional, depending on which parent they come from. The physical or functional absence of genes that are only expressed by the mother's chromosome 15 causes PWS and gentic anomalies which affects the UBE3A gen mother's copy causes AS. CONCLUSIONS: It is important to confirm the clinical diagnosis and to establish the genetic mechanism responsible for the two syndromes, both for their consequences as regards the prognosis and for genetic counselling; it is therefore important to draw up a diagnostic algorithm.

[Syndromic autism: I. General aspects]. / El autismo sindrómico: I. Aspectos generales.

INTRODUCTION AND DEVELOPMENT: The diagnosis of autism is based on the identification of certain behavioural criteria, but there is no biological test that allows us to diagnose the disorder. Yet, a considerable number of cases of autism, estimated to be somewhere between 11 and 37%, are linked to specific syndromes that can be identified according to their clinical characteristics, or by means of some biological marker. These cases are known as syndromic autism or 'double syndromes'. There is a relation between autism and certain genetic and metabolic diseases, epilepsy, infections of the nervous system, intrauterine exposure to certain substances and perinatal pathologies. CONCLUSIONS: The aim of this review is to guide the professional in the diagnosis of autistic children in order to rationalise the process by ruling out any underlying disease or syndrome related to the autistic condition. At the same time, we stress aetiological aspects of these syndromes, which make it easier to understand the biological bases of autism.

[Syndromic autism: II. Genetic syndromes associated with autism]. / El autismo sindrómico: II. Síndromes de base genética asociados a autismo.

INTRODUCTION AND DEVELOPMENT: In this study we report on the different genetic syndromes in which autism has been described as one of the possible manifestations. CONCLUSIONS: Certain genetic syndromes are providing us with extremely valuable information about the role played by genetics in autism. This is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome, 15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome, mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito, neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome.

[Mental deficiency associated with a fragility of the X chromosome]. / Deficiencia mental asociada a fragilidad del cromosoma X.

Fragile X chromosome was studied in 44 male and 9 female children, affected of mental retardation. In 10 males fragile X was positive. All this patients presented mild mental deficiency with and IQ from 55 to 75. Behaviour was generally hyperkinetic except one autistic boy. Most frequent dysmorphic signs were increased head circumference and prominent large ears. Family history for mental retardation was positive almost in all cases. High percentage of children with fragile X syndrome (22.7%) encountered among male patients suggest convenience of screening, for these anomaly, of all boys affected of mild mental deficiency and all those with an autistic behaviour although lacking of dysmorphic characteristics. This will allow to know more on etiology and to offer genetic counseling to families. Although study in girls was negative, authors believe it is interesting to screen fragile X because some females with border line retardation present this chromosomic anomaly.