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Angelman's (Happy Puppet) Syndrome: Clinical, CT Scan and Serial Electroencephalographic Study
Abstract
Of four patients having Angelman's syndrome admitted to a state mental facility who were clinically and electroencephalographically evaluated, 2 patients had CT scan studies of the brain. The most impressive and striking features that help in the diagnosis are the mental and physical retardation, nondevelopment of speech despite adequate visual and auditory function, various types of seizures, and episodic uncontrollable laughter. The CT scans of the brain did not offer any clue as to the pathogenesis. The EEGs appeared to fall into two groups: in one an arrest of electrical maturation occurred between ages 1 and 3 and in the other a slow but progressive maturation was evident.
... 24 25 On the other hand, to the best of our knowledge, no Angelman syndrome study has specifically recorded parents' views about their child's seizures and anticonvulsants, or about the eVects of treatment. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] To obtain more information about the incidence and evolution of epilepsy, patterns of seizures, treatment responses, and anti-epileptic drug side eVects in children with Angelman syndrome, we performed a study using a parental medical questionnaire in an informed group of families with a child aVected by Angelman syndrome, through one of the UK lay groups for Angelman syndrome (Angelman syndrome support education and research trust (ASSERT)). ...
... 29 30 The average age at diagnosis was lower in boys than in girls, a previously unreported observation in large series of patients with Angelman syndrome. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Many of our patients had associated medical problems and a significant number required surgery for these problems. Zori et al found similar problems in most of the British patients with Angelman syndrome but in none of the American patients. ...
... Zori et al found similar problems in most of the British patients with Angelman syndrome but in none of the American patients. 21 The overall reported prevalence of active epilepsy and recurrent afebrile seizures in our patients was similar to other reported series, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] with most of our patients with epilepsy having a detectable cytogenetic deletion. Also, seven patients had a family history of epilepsy in a first degree relative. ...
To explore parents' opinions and concerns about seizures, anticonvulsants, and the effect of treatment in children with Angelman syndrome.
A postal questionnaire was sent to members of one of the UK lay groups for Angelman syndrome (ASSERT) who had a child affected by Angelman syndrome. The questionnaire requested general medical information and information about the epilepsy, its treatment, and treatment responses.
One hundred and fifty questionnaires were sent out with an ASSERT routine mailing and 78 completed questionnaires were returned. Forty three patients were boys and 35 were girls; ages ranged from 1.7 to 25 years (mean 7.5 years). The overall general clinical and cytogenetic data were mostly consistent with previous reports. Epilepsy was reported in 68 children, most of whom had a detectable cytogenetic deletion. The most common seizure types reported by the families were absence seizures, tonic clonic seizures, drop attacks, and myoclonic seizures; in four patients only febrile seizures occurred. The age at onset of the seizures was < 2 years in more than half of the patients. Anti-epileptic drug treatment with valproate (VPA), clonazepam (CZP), and lamotrigine (LTG) as monotherapy or a combination of VPA and CZP or VPA and LTG was more often viewed favourably and considered effective with fewer side effects on the child's behaviour and alertness, versus more frequent adverse effects and increased frequency and severity of seizures with carbamazepine (CBZ) and vigabatrin (VGB) in monotherapy or in combination with other anti-epileptic drugs. Seizures did tend to improve with age but were still present and disabling at older ages.
This is the first study to record parents' opinions about seizures, anti-epileptic drugs, and treatment responses in children with Angelman syndrome, and it is one of the largest series on epilepsy and Angelman syndrome to be reported to date.
... Angel men syndrome (AS) is characterised by developmental delay, seizures, virtual absence of speech, motor impairment and a peculiar behavioural phenotype (3). Distinctive electroencephalographic (EEG) abnormalities recognised in the original patients (11) have proved consistent in subsequent studies (08, 10,11,14,17,35,55,59,81) and are included in the clinical diagnostic criteria (86). Genetic testing may confirm the diagnosis in around 85% of cases by demonstration obvious abnormalities of chromosome 15911-13 (table 1). ...
Angelman syndrome is characterised by neurodevelopmental impairment (with or without epileptic seizures) associated with functional deficit of the UBE3A gene. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity. However, three distinctive, highly consistent electroencephalographic rhythmic patterns can be observed in almost all patients irrespective of genotype, clinical severity and the presence or severity of a seizure disorder. Pattern I consists of runs of high amplitude 2 - 3/s rhythmic activity predominating over the frontal regions. Pattern II consists of more diffuse runs of 4 - 6/s rhythmic activity. Pattern III consists of bursts or runs of high amplitude 3 - 5/s rhythmic activity, maximal over the occipital region, sometimes containing small spikes and facilitated by eye closure. We review the available neurophysiological evidence from human and animal studies in the light of recent molecular advances. Electroencephalographic features in both patients and various mouse models point to two separable categories: characteristic rhythmic patterns, which are not related to epilepsy, and less specific epilepsy-related discharge activity. These features are consistent with a model of cortical and thalamo-cortical dysfunction resulting from dysregulation of synaptic GABAergic neurotransmission by (1) deficient recruitment of functional GABA (A) receptors related to reduced UBE3A gene expression in all cases and (2) decreased amount of beta3 sub-unit in these receptors related to reduced GABRB3 gene expression in deletion cases.
... The diagnosis may also be missed as polygraphic EEG recordings are not often performed in infants with epilepsy. On the other hand, considering the insidious appearance and probably the age at onset of myoclonias, the status may be unrecognized in many cases (Boyd et al., 1988;Ganji and Duncan, 1989;Van Lierde et al., 1990;Laan et al., 1997;Rubin et al., 1997). It is also probable that similar electroclinical pictures have been included by some authors in other diagnostic settings such as minor motor status, the myoclonic variant of Lennox-Gastaut syndrome or myoclonic status in symptomatic cases of myoclonic-astatic epilepsy (Brett, 1966;Gastaut, 1981;Doose, 1992). ...
Myoclonic status in nonprogressive encephalopaties (MSNE) is characterized by recurrence of long-lasting myoclonic status appearing in infants and young children with nonprogressive encephalopathy. Here, we describe the electroclinical features and evolution of MSNE.
Between February 1, 1990 and July 31, 2005, 29 patients who met diagnostic criteria of MSNE were enrolled in the study at our department and have been followed up to the present time.
Three main subgroups could be identified. The first subgroup of 18 patients presented myoclonic absences and rhythmic myoclonias. These were followed by a brief silent period related to a subcontinuous delta-theta activity involving the central areas, and rhythmic delta waves with superimposed spikes mainly involving the parietooccipital regions and often activated by eye closure. It was found in all children with a genetic etiology. The second subgroup included five patients showing a pattern characterized by inhibitory phenomena associated with a dystonic component and sudden irregular rapid lightning-like jerks. The EEG showed subcontinuous multifocal slow spike-waves, predominating in frontocentral regions. These patients are affected by a cortical malformation or the etiology is unknown. The third subgroup included six children who initially suffered from myoclonic absences. The status was initially characterized by subcontinuous generalized spike-wave-type paroxysms related to rhythmic myoclonia of face and limbs. After 1-3 weeks, the EEG showed sharp theta waves with very slow pseudorhythmic continuous spikes in the central regions and vertex. The etiology was found to be perinatal anoxic injury.
MSNE should be considered as a new epileptic syndrome in the group of epileptic encephalopathy.
We studied the clinical and EEG-findings in 28 adult patients (aged 20–53 years) with Angelman syndrome (AS). Twenty-three showed a maternal chromosome 15q11–13 deletion; in 5, the diagnosis was based on a combination of typical clinical findings. Compared to the clinical manifestations present in childhood, “coarsening” of facial traits (100%), thoracic scoliosis (71%), and being wheelchair-bound (39%) were found more frequently. Paroxysms of laughter were still observed in adulthood (79%), but less frequently than in childhood. Most adult patients could feed themselves, but needed help with many daily activities. The majority (82%) had epileptic seizures. Abnormal EEG-activity consisting of 2–3/s rhythmic triphasic waves of high amplitude with a maximum over the frontal regions, which has been identified in many AS children, was found in 67% of these adult patients. © 1996 Wiley-Liss, Inc.
We report eight sporadic cases of typical Angelman syndrome (AS) associated with chromosome 15q12 deletion. Age at first visit was 3-35 months (average 18 months), and follow-up period was 4-20 years (average 14.1 years). The characteristic features of epilepsy in AS are (a) seizure onset in early childhood (8 of 8); (b) evolution of seizure type with age (8 of 8); (c) EEG abnormality changes from high-voltage slow bursts (HVS) in infancy to diffuse spike and waves in middle childhood (4 of 5); (d) atypical absence seizures (8 of 8), often occurring as atypical absence status (4 of 8); and (e) diminution of seizure discharges and clinical seizures after puberty (7 of 7). We believe that AS may frequently exist in the intractable epilepsies of childhood with severe mental retardation. We stress the importance of AS as one of the main etiologic background diseases of the intractable epilepsies with infantile onset such as West syndrome, Lennox-Gastaut syndrome, and others.
To further delineate the clinical and developmental features of Angelman syndrome, we collected data through three sources of information: (1) physical examinations; (2) laboratory data and family questionnaire data of affected individuals; and (3) literature review. The questionnaire data describes a generally normal prenatal and birth history. Feeding difficulties, developmental delay, or seizures were the presenting problems in all infants. The diagnosis of Angelman syndrome, however, was not made in any infant prior to 1 year of age. Except for seizures, no medical or surgical complication was common, although a variety of visual complaints or findings were common. Sixty percent of Angelman syndrome children had a cytogenetically demonstrated deletion of chromosome 15q11-q13. The individuals with and without a deletion could not be differentiated clinically. Diagnosis in early childhood is therefore difficult, and a high index of suspicion is recommended.
We report the neuropathological findings of a 3-year-old boy with Angelman's syndrome. The main abnormalities were macroscopic consisting of small temporal and frontal lobes which also showed disorganised and irregular gyri. The occipital lobes appeared flattened but were otherwise normal as were the parietal lobes. The brain stem and cerebellum appeared normal externally. Microscopically there was irregular distribution of neurons in layer 3 and in the cerebral white matter a few subcortical ectopic neurons were present in the temporal and frontal lobes. A single "Purkinje" cell heterotopia was seen but otherwise the cerebellum appeared normal.
Laughter is a partly involuntary act involving complex pathways in the central nervous system. Laughter normally has positive effects on emotions; however, pathologic laughter is not related to emotion and occurs independent of a stimulus in the environment. This paper outlines normal laughter and the etiology of pathologic laughter, considering both congenital and acquired causes.
Angelman Syndrome usually has been considered to be rare and sporadic. However, recent reports suggest a sibling recurrence risk of just under 25 per cent, so early diagnosis is very important. The authors report Angelman Syndrome in a child of seven months. The early features of this Syndrome (jerky movements, EEG characteristics, chromosomal abnormalities in half the cases) should make it possible to diagnose or suspect the Syndrome in the first year of life.
Syndrome d'Angelman durant la première année de vie
Le Syndrome d'Angelman a été habituellement considéré comme rare et sporadique. Cependant, des articles récents suggérent un risque de réapparition dans la fratrie juste en dessous de 25 pour cent, et le diagnostic précoce est donc trés important. Les auteurs rapportent le cas d'un Syndrome d'Angelman chez un enfant de sept mois. Les caractéristiques précoces de ce Syndrome (mouvements brusques, caractéristiques particulières à l'EEG, anomalies chromosomiques dans la moitié des cas) deraient rendre possible le diagnostic ou suspecter le Syndrome au cours de la première année de vie.
Angelman Syndrom im ersten Lebensjahr
Das Angelman Syndrom wurde bisher als selten und sporadisch auftretend angesehen. In neueren Berichten wird jedoch von einem knapp 25-prozentigen Wiederholungsrisiko bei Geschwistern gesprochen, sodaß die Frühdiagnose sehr wichtig ist. Die Autoren berichten über ein Angelman Syndrom bei einem sieben Monate alten Kind. Die Frühmerkmale dieses Syndromes (krampfhafte Bewegungen, EEG-Charakteristika Chromosomenanomalien in der Hälfte der Fälle) sollten es möglich machen, das Syndrom im ersten Lebensjahr zu diagnostizieren oder zu vermuten.
Síndrome de Angelman en el primer año de vida
El síndrome de Angelman ha sido considerado habitualmente como raro y esporádico. Sin embargo aportaciones recientes sugieren un riesgo de recurrencia en hermanos de casi el 25 por ciento, por lo que es muy importante su diagnóstico precoz Los autores aportan un caso de sindrome de Angelman en un niño de siete meses. Los signos precoces de este síndrome (sacudidas, EEG característico, anomalías cromosómicas en la mitad de los casos) harían posible su diagnóstico o su sospecha en el primer año de vida.
We describe 47 patients with Angelman syndrome (AS) from Belgium and the Netherlands, including the anamnestic data, the clinical and the behavioral attributes at different ages. The clinical picture of AS is most distinct between the ages of 2-16 years. Most patients of this age group show at least 8 of the major characteristics (bursts of laughter, happy disposition, hyperactive behaviour, microcephaly, brachycephaly, macrostomia, tongue protrusion, mandibular prognathism, widely spaced teeth, stiff and puppetlike movements, typical stature, wide based gait) beside the mental retardation and (almost) absence of speech, which is a universal trait. The diagnosis in infants is based on only a limited number of clinical characteristics or on anamnestic data. However, if these occur in combination, they are indicative of AS. In older patients, the diagnosis may be hampered in part because of the changing behavioral characteristics and the decreasing frequency of fits. Other manifestations, such as scoliosis, may become more pronounced with age.
CT findings on 170 patients presenting with isolated moderate to severe neurodevelopmental delay have been compared with the final diagnosis. MRI was undertaken in 29 patients. Eighty per cent of the patients remained undiagnosed, and although the MRI findings were abnormal in 65.5% compared with only 30% of the CT examinations, imaging uncommonly suggested a specific diagnosis. Biochemical and chromosomal investigations were significantly more diagnostic. The results of these studies should restrict the number of non-contributory neuroradiological examinations. The superior intrinsic contrast of MRI will detect more lesions, particularly in white matter, but these are rarely diagnostic and where access to MRI is limited, CT is usually adequate.
The authors describe 7 new cases of Angelman syndrome (AS: 3 males and 4 females) diagnosed on the basis of clinical features (dysmorphic facial features, severe mental retardation with absent speech, peculiar jerky movements, ataxic gait and paroxysms of inappropriate laughter) and neurophysiological findings. Failure to detect deletion of the long arm of chromosome 15 or the absence of epileptic seizure were not considered sufficient to exclude a diagnosis of AS. Feeding problems, developmental delay and early signs of ataxia, especially tremor on handling objects and unstable posture when seated, proved effective as clinical markers for early diagnosis of AS. The EEG patterns characteristic of AS were found within the first 2 years of life (under 18 months in the majority of cases). The authors conclude that AS should be included in differential diagnosis in a child aged under 12 months having cryptogenic psychomotor retardation with prevalent language compromise. Repeat EEG recordings are needed to check for the typical trace, and cytogenetic investigations are mandatory.
Angelman syndrome (AS) is a genetic disorder that is associated with a deletion on chromosome 15, and is characterized by abnormalities or impairments in neurological, motor and intellectual functioning. While behaviour problems have been reported in clients with AS, relatively little is known about their developmental course and outcome. In this study, data on the nature and prevalence of behaviour problems among clients with AS were gathered from two sources: (1) a review of published case reports; and (2) parent responses to a survey of behaviour problems in a small (n = 11) sample of children with AS. Data from both sources showed that behaviour problems were present in males and females of all ages, and included language deficits, excessive laughter, hyperactivity, short attention span, problems with eating and sleeping, aggression, noncompliance, mouthing of objects, tantrums, and repetitive and stereotyped behaviour. Identification and treatment of severe behaviour problems in clients with AS may improve their adaptive functioning.
We studied the seizure and polygraphic patterns of 18 patients with Angelman's syndrome. All patients showed movement problems. Eleven patients were also reported to have long-lasting periods of jerky movements. The polygraphic recording showed a myoclonic status epilepticus in nine of them. Seven patients had partial seizures with eye deviation and vomiting, similar to those of childhood occipital epilepsies. These seizures and electroencephalographic patterns suggest that Angelman's syndrome occurs in most of the patients as a nonprogressive, age-dependent myoclonic encephalopathy with a prominent occipital involvement. These findings indicate that, whereas ataxia is a constant symptom in Angelman's syndrome, the occurrence of a transient myoclonic status epilepticus may account for the recurrence of different abnormal movements, namely the jerky ones.
To evaluate the evolution of epileptic seizures and EEG features in a large group of patients with Angelman syndrome (AS).
Thirty-six patients with AS with a proven chromosome 15q11-13 deletion were retrospectively analyzed with regard to their epilepsy and EEG findings by examination of patient files and EEGs. AIJ EEGs were reviewed by one of the authors. A logistic regression model, with a follow-up from 1 to 39 years (mean, 15 years), was used for statistical analysis.
Epileptic seizures had occurred in 30 (83%) patients. In 43% of them, the initial symptoms of epilepsy were febrile convulsions in infancy. In childhood, epilepsy could start with almost any type of seizure. Atypical absences and myoclonic seizures prevailed in adulthood. Epileptic seizures were present in 92% of the adult patients. The most typical EEG findings were rhythmic triphasic delta waves of high amplitude with a maximum over the frontal regions, identified in 99 (66%) of 150 EEGs, and continuously or intermittently, in 30 (83%) of 36 patients with AS. In 47% it was present even before a clinical diagnosis of AS was considered. High-amplitude rhythmic 4-6/s slow activity, seen in 44 (29%) of 150 EEGs, was not present after the age of 12 years.
In contrast to previous reports suggesting a decreasing frequency of epileptic seizures with age, we found that 92% of the adult patients with AS continued to have epileptic seizures. The most typical EEG finding in AS, in both children and adults, was the presence of frontal triphasic delta waves. In mentally retarded patients, this EEG pattern should point the physician in the direction of AS.
Angelman's syndrome is a rare genetic disorder characterized by developmental delay, craniofacial abnormalities, ataxia, paroxysmal laughter, and seizures. The diagnosis is suspected in infants who have the characteristic clinical features and electroencephalographic (EEG) abnormalities and is confirmed by the genetic identification of a maternally derived 15q11-13 deletion. We report on 3 patients with genetically confirmed Angelman's syndrome who had the characteristic clinical and EEG features. The EEGs demonstrated high-amplitude 2- to 3-Hz delta activity, with intermittent spike-and-slow-wave discharges maximal in the occipital region in 2 patients and generalized sharp-and-slow-wave discharges, occipital spikes, and electrographic status epilepticus during slow-wave sleep in the other patient. The findings of generalized high-amplitude delta slowing and occipital spike-and-wave discharges, facilitated by eye closure, in children with developmental delay and seizures suggest the diagnosis of Angelman's syndrome and should lead to genetic testing.
We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11-13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed-circuit television videotaping and digitized electroencephalogrpahic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched class II, III, and IV patients had either no epilepsy or drug-responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as GABRB3, may explain severe epilepsy in AS.
We report on a sib pair who manifest a pattern of anomalies which appears to be unique and for which we are unable to provide a cytogenetic or molecular genetic explanation. While a number of their physical features are distinct, their overall appearance and pattern of neurological impairment suggest they suffer from the same genetic disorder.
In order to evaluate which diagnostic criteria can be indicative for an early diagnosis of Angelman syndrome (AS), 144 children with severe epilepsy and mental retardation were evaluated. In 10 of them the diagnostic criteria indicated by Williams were present. Of the remaining 134 patients we were able to diagnose one 15-year-old patient with AS, on the basis of the EEG findings, even though the typical clinical features of the syndrome were absent. In all patients the diagnosis of AS was confirmed by fluorescent in situ hybridization (FISH) in 10 patients and by methylation analysis in one patient. AS is very likely when both typical clinical and EEG findings are present. Nevertheless, it must be considered in all patients affected by severe epilepsy and mental retardation, when the EEG pattern is sufficiently indicative, and FISH and/or molecular analysis should be performed even in absence of typical clinical signs.
Differential diagnosis in a newborn with dysmorphic features and profound neurologic dysfunction should include the cerebro-hepato-renal syndrome of Zellweger. Its distinct clinical features, markedly elevated plasma levels of very long chain fatty acids and characteristic radiological findings support the diagnosis, which can now be confirmed by genetic markers. Quite consistent abnormalities of the neurophysiological studies in this syndrome have also been reported. We report a case with typical clinical and biochemical findings in whom distinctive brain MRI abnormalities were found. The results of neurophysiological studies with an unusual EEG pattern of continuous negative vertex sharp waves and spikes are discussed. We believe that such a pattern could be considered as a pathognomonic EEG finding, especially in cases of Zellweger syndrome with extensive brain abnormalities and may even be closely associated with cortical dysplasias.
Three children with mental and physical retardation and with other features compatible with Angelman's ‘happy puppet’ syndrome are presented. Significant features of these children and the six previously published cases are tabulated. It now seems likely that this syndrome is a definite clinical entity, although the aetiology is still unknown.
Trois nouveaux cas de ‘Marionnettes heureuses’
Trois enfants avec retard mental et physique et avec d'autres manifestations correspondants au syndrome de ‘Marionnette heureuse’ de Angelman sont étudiés. Les caractéristiques significatives de ces enfants et des six cas déjá publiés sont analysés. II semble maintenant très vraisemblable que ce syndrome soit une entité clinique définie quoique l'étiologie en soit encore inconnue.
Weitere drei ‘Happy Puppets’
Es werden drei Kinder beschrieben, die außer geistiger und motorischer Retardierung noch andere Merkmale aufwiesen, wie sie bei Angelman's ‘Happy Puppet’ Syndrom beschrieben sind. Die wichtigsten Symptome dieser Kinder und der sechs früher veröffentlichten Fälle sind in einer Tabelle zusammengestellt. Man könnte sagen, daß dieses Syndrom ein umrissenes klinisches Krankheitsbild darstellt, von dem die Ätiologie jedoch noch unbekannt ist.
Tres ‘felices muñecas’ más
Se describen tres niños con reraso mental y fisico y otras características compatibles con el síndrome de Angelman ‘felices muñecas’. Se exponen las características significativas de estos niños y de los seis casos publicados anteriormente. Parece probable actualmente que el sindrome sea una entidad clinica definida, aunque la etiologia es aún desconocida.
. Two cases of happy puppet or Angelman syndrome are presented. They have the typical clinical features and represent the first Swedish cases. One of the patients is a man of 75 years of age, which shows that this form of severe mental retardation is well compatible with long life. Extended EEG monitoring may identify the typical EEG abnormality when this is difficult to demonstrate in routine EEG records. The typical laughter has no specific correlate in the EEG and thus is probably not an epileptic manifestation. Regional cerebral blood flow studies were normal in the young patient (11 years of age) but in the older patient showed a reduced cerebral circulation, compatible with organic dementia
The EEG development of sigma rhythm (sleep spindles) has been studied in normal and hypothyroid infants. Work by others in infant animals has shown that there is a close relationship between the appearance of this rhythm and brain maturation. In this study, all hypothyroid infants initially showed a decrease from normal or an absence of sigma rhythm. After thyroid therapy some developed normal amounts of this activity but others continued to show less sigma rhythm than control infants. Those infants that developed normal sigma rhythm activity tended to demonstrate normal developmental quotients on follow-up evaluation, whereas those that did not showed lower developmental quotients. The results show that in cretinism there is a delay in the bioelectric and neurophysiological development of the brain and suggest that in some cases there is a continued deficit of neuronal function or integration after treatment with thyroid hormone.
We analyzed 320 electroencephalograms done on 60 patients having tuberous sclerosis. The main features in EEGs were diffuse slowing in the background activity, slow spike-wave discharges, focal and multifocal spike discharges, and amplitude asymmetries. No significant changes occurred in EEGs during the follow-up. No characteristic pattern was identified for diagnosing TS. Severe abnormalities were seen in patients who had infantile spasms and frequent seizures, and who were mentally retarded. Slow spike-wave abnormality was less frequent in patients who had mild mental retardation and few seizures. The pathological findings did not offer any clue to the frequently recorded EEG abnormalities.
Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine "dysgenesis" is a common feature of the microstructural pathology that occurs in profound mental retardation of unknown etiology.
The main features of the “Happy Puppet” Syndrome are severe motor and intellectual retardation, ataxia, hypotonia, characteristic facies with a large mandible, and epilepsy. The E. E. G. shows bilateral high amplitude spike and wave activity, the slow wave component being at 2 c. sec. Two children with these features are compared with the five previously reported cases. The condition is non-progressive. The aetiology is unknown and there is no specific treatment.
Nine children with the ‘happy puppet’ syndrome are presented here and 19 previously reported cases are reviewed. A characteristic psychological profile is suggested by the children's ‘unfocused’ activities and inconsistent responsiveness to their surroundings. Behavioral characteristics are atypical for mental age and do not appear to represent unusual seizure equivalents. Recognition of such non‐adaptive behavior may be of importance n selecting specific treatment and management techniques to modify the characteristics of this syndrome at an early age.
RÉSUMÉ
Corrélation comportementale dans le syndrome de la marionnette heureuse: profil caractéristique?
Neuf enfants atteints du syndrome de la ‘marionnette heureuse’ sont décrits et 19 cas antérieurement rapportés sont étudiés. Un profil psychologique caractéristique est suggéré par les activites ‘non orientées’ des enfants et une résponse inadaptée á l'environnement. Les caractéristiques du comportement sont atypiques pour l'âge mental et ne peuvent s'expliquer par des équivalents comitiaux inhabituels. La reconnaissance d'un tel comportement non adapté peut être importante pour établir un traitement spécifique et suggérer des conseils pour modifier les caractéres de ce syndrome á un âge précoce.
ZUSAMMENFASSUNG
Verhaltenskorrelate beim Happy Puppet Syndrom: ein charakteristisches Profil?
Neun Kinder mit einem ‘Happy Puppet’ Syndrome werden hiervorgestellt und 19 bereits beschriebene Fälle werden erwähnt. Durch die ‘ungezielten’ Aktivitäten der Kinder und das wechselnde Verhalten ihrer Umwelt gegenüber wird vermutet, daß ein charakteristisches psychologisches Profil vorliegt. Die Verhaltensmerkmale sind für das geistige Alter untypisch und es scheint nicht so, daß sie ungewöhnliche Krampfäquivalente darstellen. Das Erkennen eines solchen nicht angepaßten Verhaltens ist wichtig, urn spezifische Behandlungs‐ und Führungsempfehlungen zur möglichst frühzeitigen Beeinflussung der Charakteristika dieses Syndromes geben zu können.
RESUMEN
Correlación de comportamiento en el síndrome de la muñeea feliz: es un perfil característico?
Nueve niños con el síndrome de la ‘muñeea feliz’ son presentados aquí y se revisan 19 casos previamente aportados. Se sugiere un perfij psicologico característico presentado por los nin̂os con actividad ‘no focalizada’ y con respuestas inconsistentes a su peristasis. Las características del comportamiento son atípicas con respecto a la edad mental y no parece que representen equivalentes raros de convulsiones. El reconocimiento de este comportamiento no adaptativo puede ser de importancia para selecionar el tratamiento especifico y las recomendaciones para el trato de estos nin̂os para modificar las características de este síndrome en una fase precoz de la vida.
Two siblings with the "happy puppet" syndrome are presented. Their clinical features are quite similar and closely resemble those of previously reported cases. These features include severe mental retardation, epileptic seizures, easily provoked and prolonged paroxysms of laughter, atactic jerky movements, hypotonia, large mandible with prognathia, and 2-3 cps spike and wave activity in the EEG. The occurrence of this syndrome in the two siblings suggests a genetic etiology possible as an autosomal recessive trait.
In the course of electroencephalographic studies on patients with epilepsy an abnormal pattern has been found that is peculiar to infants and young children. It occurs in patients with brief quivering spells, myoclonic jerks or spasms.1 This pattern (chart 1) has been called hypsarhythmia (mountainous arhythmia) and the clinical state with which it is associated is referred to as infantile spasms.
The present report is based on 237 cases with hypsarhythmia and infantile spasms. For the most part this group is made up of patients who were referred for electroencephalographic study by private physicians in the Chicago area; a few came from the Department of Pediatrics at the University of Illinois School of Medicine; 60% were males and 40% were females. On referral they bore such diagnostic labels as "colic," "petit mal epilepsy," "myoclonia," "spasms nutans" and "spasmophilia."