Marian A. Maaskant

Is Sanfilippo Type B in Your Mind When You See Adults With Mental Retardation and Behavioral Problems

Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N‐acetyl‐α‐D‐glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18–63 years old. Apart from the youngest, they had lost mobility at 36–68 years. Most had developed physical problems, in particular in the 4th–6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS.

Psychiatric illness in a cohort of adults with Prader-Willi syndrome

Previous studies have suggested an association between PWS and comorbid psychiatric illness. Data on prevalence rates of psychopathology is still scarce. This paper describes a large-scale, systematic study investigating the prevalence of psychiatric illness in a Dutch adult PWS cohort. One hundred and two individuals were screened for psychiatric illness. Case vignettes were written by the first author on 63 individuals with a positive screening on psychopathology according to the interviews, medical history, medication use and behavioural questionnaires. These case vignettes were rated by two psychiatrists specializing in intellectual disability (ID). Psychopathology was divided into four diagnostic categories: bipolar disorder with psychotic symptoms, psychotic illness, depressive illness with psychotic symptoms and depressive illness without psychotic symptoms. Nine out of 53 persons (17%) with a 15q11-13 deletion and 28 out of 44 (64%) persons with maternal uniparental disomy (mUPD) were diagnosed with a current or previous psychiatric illness. Depressive illness with psychotic symptoms was the cause of psychiatric problems in the majority of persons with PWS due to deletion (56%). In the case of mUPD, almost all individuals with histories of psychopathology suffered from psychotic symptoms (85%) with or without affective component. Psychiatric examination should be part of general management of adults with PWS, especially when caused by mUPD. More attention should be paid to the presence of precursor symptoms, indicating a developing psychiatric episode. Longitudinal studies are needed to gain more insight into the natural history of psychiatric illness in adults with PWS.

Behavioral phenotype in adults with Prader–Willi syndrome

Prader-Willi syndrome (PWS) is characterized by temper tantrums, impulsivity, mood fluctuations, difficulty with change in routine, skinpicking, stubbornness and aggression. Many studies on behavior in PWS are limited by sample size, age range, a lack of genetically confirmed diagnosis of PWS and inconsistent assessment of behavior. The aim of this study was to explore systematically the relation between behavioral problems and age groups, genetic subtypes and BMI categories in an adult PWS population. Participants were contacted via the Dutch Prader-Willi Parent Association and through physicians specialized in persons with ID. Behaviors were studied using the Developmental Behavior Checklist for Adults (DBC-A). The forms were completed by the main caregivers of 98 adults with a genetically confirmed diagnosis of PWS. Differences between age groups were statistically significant (ANOVA, p=0.03). DBC-A total scores were higher in the consecutive age groups, with the most behavioral problems in the oldest age groups. Differences between genetic subtypes were also statistically significant (ANOVA, p<0.01). Persons with mUPD had higher total scores on the DBC-A than persons with a deletion. Those with a Type I deletion showed higher total DBC-A scores than persons with a Type II deletion. There were no statistically significant differences in DBC-A total scores between the different BMI categories. Individuals with a BMI<25 had higher scores on the self-absorbed subscale compared to persons with a BMI between 25 and 30. Unlike previous descriptions of the behavioral phenotype in adults with PWS, we did not find a reduction in behavioral problems in older adults. Therefore, special attention should be paid to behavioral problems as part of general management of adults with PWS. Longitudinal studies are warranted to gain more insight into the natural history and course of behavioral problems in adults and older people with PWS over the long term and possible risk and preventive factors.

Aging in people with specific genetic syndromes: Rett syndrome

The aging process of people with intellectual disabilities has been a topic of interest in recent years. Good knowledge of the specific healthcare problems in adults with intellectual disabilities and anticipating on these problems are important issues in providing support and healthcare for these persons. Nevertheless little is known about the aging process of people with specific syndromes, like Rett syndrome. In association with the Dutch Rett syndrome parent association, 70 postal questionnaires were sent to the contact persons of the females aged at least 16 years with a clinical diagnosis of Rett syndrome. The questionnaire consisted of general questions, questions about living conditions, skills, physical and psychiatric morbidity. The response rate was 76% (n = 53). In general adults with Rett syndrome seemed to be reasonably healthy, whereas neurological, respiratory and behavioral morbidity appeared to be of great influence. High care dependency was confirmed. In contrast with underweight, overweight showed to be an under‐ascertained feature. The general disorder profile was confirmed, considering the increase with age regarding kyphosis and the better communication and autonomic dysfunction in the oldest age group compared to the younger age groups. Features of autonomic dysfunction deserve more medical attention, especially the interrelation between quality of sleep, respiration and behavior in Rett syndrome. Longitudinal studies including genotype–phenotype analyses are needed for insight in individual changes in support needs and health.

Sleep disturbances and behavioural problems in adults with Prader-Willi syndrome.

BACKGROUND Individuals with Prader-Willi syndrome (PWS) are at risk of sleep disturbances, such as excessive daytime sleepiness (EDS) and sleep apnoea, and behavioural problems. Sleep disturbances and their relationship with other variables had not been researched extensively in adults with PWS. METHOD Sleep disturbances and behavioural problems were investigated in adults with genetically confirmed PWS using standardised questionnaires. Results of adults with paternal deletion (n=45) were compared with those of adults with maternal uniparental disomy (n=33). RESULTS Eleven adults with PWS (i.e. 15%) had a current sleep problem, mostly night waking problems. Twenty-six adults with PWS (i.e. 33%) suffered from severe EDS. No differences in prevalence of sleep disturbances between genetic subtypes were found. Seventeen adults with deletion (i.e. 38%) and 17 adults with maternal uniparental disomy (i.e. 52%) had behavioural problems. No significant relationships were found between sleep disturbances and behavioural problems. CONCLUSIONS In adults with PWS, EDS is the most common type of sleep disturbance. Men and individuals with relative high body mass index are at increased risk for EDS. More research, aimed at developing a suitable screening instrument for sleep apnoea in adults with PWS, is necessary. Clinical implications of the findings are discussed.

The relationship between challenging behaviour and anxiety in adults with intellectual disabilities: a literature review

BACKGROUND Anxiety and challenging behaviour (CB) often occur simultaneously in people with intellectual disabilities (ID). Understanding the associations between anxiety and CB may contribute to more accurate diagnoses and management of both anxiety and CB in this population. AIMS To examine the relationship between anxiety and CB. METHODS A literature review covering the period from January 2000 to January 2012. RESULTS Seven studies about the relationship between psychiatric disorders, including anxiety, and CB were identified. These studies confirm the relationship between anxiety and CB in people with ID, although the precise nature of this relationship remains unclear. CONCLUSIONS The study points toward the existence of a moderate association between anxiety and CB. Further research is needed to clarify the complex nature of the association between anxiety and CB.

Healthcare transition in persons with intellectual disabilities: General issues, the Maastricht model, and Prader–Willi syndrome†

In current healthcare, transitional healthcare is a very important and timely issue. Thanks to the major advances made in medical care and technology, many children with childhood onset diseases and/or genetic syndromes survive to adulthood. These children are at risk of not being provided with adequate healthcare as they reach adulthood. Healthcare transition is an essential part of healthcare provision, referred to as the shift from one type of healthcare to another. In Maastricht, we developed a transition/out clinic led by a medical doctor specialized in persons with intellectual disability (ID), together with a clinical geneticist. We aim to coordinate healthcare issues based on guidelines if available. Also questions concerning living, daily activities, relations, sexuality, and sterilization can be discussed. The aging process of persons with ID has been a topic of interest in recent years. Little is known about the aging process of people with specific syndromes, except for persons with Down syndrome. We present some data of a recent questionnaire study in persons with Prader–Willi syndrome. In only 50% in persons with a clinical diagnosis genetic test results could be reported. The majority of persons were obese. Diabetes mellitus, hypertension, skin problems, sleep apnea, and hormonal problems like osteoporosis and hypothyroidism were common. Psychiatric problems were frequent, especially in the persons with uniparental disomy. Osteoporosis and sleep apnoea seem to be underestimated. Further longitudinal research is necessary for a better understanding of the aging process in PWS.

Genotype–phenotype relationships as prognosticators in Rett syndrome should be handled with care in clinical practice†‡

Rett syndrome (RTT; OMIM 312750) is an X‐linked dominant neurodevelopmental disorder leading to cognitive and motor impairment, epilepsy, and autonomic dysfunction in females. Since the discovery that RTT is caused by mutations in MECP2, large retrospective genotype–phenotype correlation studies have been performed. A number of general genotype–phenotype relationships were confirmed and specific disorder profiles were described. Nevertheless, conflicting results are still under discussion, partly due to the variability in classification of mutations, assessment tools, and structure of the data sets. The aim of this study was to investigate relationships between genotype and specific clinical data collected by the same experienced physician in a well‐documented RTT cohort, and evaluate its prognostic value in counseling young parents with a newly diagnosed RTT girl regarding her future outcome. The Maastricht–Leuven Rett Syndrome Database is a register of 137 molecularly confirmed clinical RTT cases, containing both molecular and clinical data on examination and follow up by the same experienced physician. Although the general genotype–phenotype relationships were confirmed, the clinical severity was still found to be very variable. We therefore recommend caution in using genotype–phenotype data in the prognosis of outcome for children in Rett syndrome. Early diagnosis, early intervention, and preventive management are imperative for better outcomes and better quality of daily life for RTT females and their families.

The use of contraception by women with intellectual disabilities

BACKGROUND Worldwide, contraception is frequently used by women for the prevention of conception, to regulate or postpone menstrual bleeding. The study aims to determine the use (number and method) of contraception by women with intellectual disabilities (ID), the indications, sources of referrals and relations with level of ID and age of the women concerned. METHODS The study group consisted of 234 women aged between 15 and 59 years and residing at a Dutch service provider for persons with ID. Data were obtained via the pharmacy database, attending physicians and individual medical files. RESULTS Nearly one half (48%, n = 112) of the 234 residential women used some method of contraception: 87 (78%) took pharmacological contraceptive methods, 23 (20%) underwent surgical contraception and 2 (2%) both. Main reasons for contraception were problems with menstruation, behaviour and/or prevention of pregnancy. Requests for contraception were initiated mainly by physicians and parents. Differences between users of different contraceptives with regard to age and level of ID were not statistically significant. CONCLUSIONS Further studies should focus on the development and implementation of adequate health promotion materials on this subject.

Aging in Prader–Willi syndrome: Twelve persons over the age of 50 years†

The life expectancy of persons with Prader–Willi syndrome (PWS) has increased in recent years. Because of the paucity of reports on older persons with PWS, the natural history, the onset, and type of age‐related problems are poorly understood. Twelve persons with a genetically confirmed diagnosis of PWS aged over 50 years are described (4 deletion; 8 mUPD). Data on physical, behavioral, psychiatric, and aging characteristics were collected through semi‐structured interviews with the individuals with PWS and their main carers. Cardiovascular diseases, diabetes, dermatological, and orthopedic problems were common physical complaints in older people with PWS. Functioning in activities of daily living, psychological functioning, physical functions, and care dependence were substantially worse in the older age group (50+) compared to the control group (18–49 years). Seven out of eight persons with mUPD had a history of psychiatric illness. Behavioral problems were observed in the older age group. Given the combination of age‐related physical morbidity, physical appearance, behavioral and psychiatric problems, and functional decline in our cohort, we hypothesize that premature aging occurs in PWS. The care for older people with PWS requires a lifespan approach that recognizes the presence, progression, and consequences of specific morbidity. Special medical surveillance of people with PWS from 40 years onwards would ensure that intervention and support is offered with respect to specific areas of decline at the earliest possible time.