BEHAVIOURAL PHENOTYPES IN ADULTHOOD
Gregory O'Brien
Behavioural phenotypes are syndromes with a chromosomal or genetic aetiology (Skuse, 2002), comprising both physiological and behaviour manifestations, including a distinctive social, linguistic, cognitive and motor profile (O'Brien et al., 2002). The course of the syndrome, both behaviourally and medically, is not stagnant, and the presentation of the syndrome can vary according to level of intellectual disability and input received, and can change with increasing age.
Intellectual disability in behavioural phenotypes
While Down's syndrome is the most common cause of intellectual disability, fragile-X
syndrome is the most common inherited cause of learning disability (see Sabaratnam,
2003). The level of intellectual disability can be affected by severity of the
phenotypic expression. In a number of syndromes, such as Cornelia de Lange,
milder phenotypic expression is associated with less severe intellectual disability.
Sex differences can also determine level of intellectual disability; for example,
females with fragile-X syndrome have milder phenotypic expression and less severe
intellectual disability. Figure 1
shows the typical level of intellectual disability for a range of genetic syndromes.
Owing to the range of intellectual disability exhibited across behavioural phenotypes,
it is important to assess cognitive functioning at an early stage, particularly
when the level of intellectual disability may be borderline, as in the case
of Sotos and Turner syndromes, so that educational intervention can be tailored
to meet the individual's needs and maximize the individual's potential (Barnard
et al., 2002).
Behavioural phenotypes and aberrant behaviours
Aberrant behaviours such as self-injury, screaming and aggression are common
in behavioural phenotypes. This finding is not surprising given that these behaviours
are highly prevalent in the population of people with intellectual disabilities,
and are more common in people with severe intellectual disability. In a number
of syndromes, such as Lesch-Nyhan syndrome, self-injurious behaviour is a primary
behavioural feature of the syndrome. Although the underlying origin of these
behaviours can sometimes be linked to a biological mechanism, such as a deficiency
in the enzyme hypoxanthineguanine phosphoribosyl transferase (HPRT) in Lesch-Nyhan
syndrome, in most conditions the pathway from gene to behaviour is less clear.
Reasons for aberrant behaviour
Aberrant behaviours such as self-injury and aggression can be indicative of
physical pain. Head-banging is often associated with dental pain or upper respiratory
tract infections causing sinusitis or otitis (Clarke, 2002) or gastrointestinal
reflux, as commonly occurs in Cornelia de Lange syndrome. Another explanation
for behaviours such as temper tantrums and irritability is frustration at being
unable to communicate needs. In this instance, alternative ways to promote communication,
either through sign language or pictorial representations, depending on the
individual's level of ability, should be considered to alleviate the behaviour
(see also Joyce, 2003). Speech and language therapy can also be used in order
to maximize the individual's verbal ability (Barnard et al., 2002). Behavioural
therapies are useful in identifying and alleviating the function of these behaviours.
A multidisciplinary approach to treatment is advocated, incorporating pharmacological
therapy, physical restraint and behavioural therapy. Fortunately, behaviours
such as self-injury often become less prevalent with age.
Psychiatric disorders
In adulthood, the propensity for psychiatric disturbance often increases. Anxiety
and depression are frequently cited in the behavioural phenotypes of a number
of syndromes (see Figure 2).
However, this presents a paradox, as symptoms of a psychiatric disorder may
be overshadowed by the behaviour and intellectual disability of affected individuals.
Also, the presentation of a psychiatric disorder in people with intellectual
disability is often atypical, further confounding diagnosis. If a psychiatric
diagnosis is suspected, assessment using a schedule designed for use in intellectual
disability is recommended (O'Brien et al., 2001). In spite of the prevalence
of autistic-like behaviours in many syndromes, autism is typically associated
with a few conditions only, notably tuberous sclerosis.
In syndromes in which there are differences in physical appearance, such as
short stature/accelerated growth, facial dysmorphism or delayed sexual development,
affected individuals can suffer from low self-esteem and this can often precipitate
secondary behavioural difficulties. The prevalence of psychiatric disorders
in behavioural phenotypes has directed research towards investigation of a genetic
component of psychiatric disorders.
Aberrant behaviours, especially when extreme in severity (such as self-injury)
are particularly distressing for both affected individuals and their carers.
Practitioners should offer support to both parties, and reassurance and support
should also be offered to family members and carers, as they can often perceive
themselves to be the cause of the individual's behaviour.
Medical complications
In general, severity of intellectual disability is associated with an increase
in associated medical conditions and complications (O'Brien et al., 2002). The
relationship between medical complications is complex; they interact with one
another, rarely appear in isolation within the same syndrome, and can manifest
secondary medical and behavioural complications. Fortunately, preventative measures,
such as good diet and physiotherapy, can ameliorate the consequences of medical
and behavioural complications. Clinicians should be aware that medical complications
associated with the presentation of the behavioural phenotype in childhood can
change as the individual reaches adulthood.
Respiratory disorders are a major cause of morbidity and distress in
individuals with behavioural phenotypes. Common respiratory disorders include
aspiration pneumonia, congenital defects and recurrent respiratory infections.
Hypotonia, scoliosis and cardiac anomalies are common causes of respiratory
insufficiency. Physiotherapy is a useful intervention for breathing difficulties
associated with hypotonia. However, practitioners should be aware that a number
of interventions are associated with difficult complications, for example surgical
interventions to help alleviate breathing difficulties present a significant
anaesthesia risk in a number of syndromes. Tube-feeding for individuals with
failure to thrive (both children and adults) can contribute to respiratory infection.
Respiratory complications impact on all aspects of functioning, for example
by disturbing sleep. In syndromes characterized by an atypical sleep pattern,
such as Sanfilippo syndrome, this can be extremely distressing and can contribute
to behavioural disturbances.
Cardiovascular complications: the cardiovascular system is involved in the morbidity and mortality associated with a number of genetic syndromes in which behavioural phenotypes present. Congenital heart defects are common and affect individuals with fragile-X, Down's and Rubenstein-Taybi syndromes (Barnard et al., 2002). Cardiac abnormalities can be associated with muscular and skeletal degeneration. Abnormalities of the cardiovascular system can contribute to secondary complications, such as hypertension in Williams and Turner syndromes. Cardiovascular disease can be secondary to obesity, particularly in Prader-Willi syndrome. In managing these cardiovascular complications, routine ECG screening and promotion of a healthy diet is advocated.
Obesity: in a number of syndromes, such as Angelman and Rubenstein-Taybi syndromes, associated feeding difficulties such as failure to thrive in childhood can manifest into a propensity for obesity in adulthood. Obesity can lead to serious medical problems, such as non-insulin-dependent diabetes mellitus, hypertension and cardiovascular disease. In some syndromes, such as Prader-Willi syndrome, the propensity for obesity is one of the cardinal features, and is potentially life-threatening. Dietary intervention at an early stage can help counteract and minimize secondary medical complications. Intervention techniques such as restricting sources of food (e.g. by locking the refrigerator) and managing calorific intake are effective. Behavioural modification strategies that have an emphasis on self-monitoring and reinforcement, in combination with exercise programmes, can be effective in maintaining a healthy weight.
Epilepsy associated with behavioural phenotypes can be difficult to
manage. The presentation of epilepsy varies according to the syndrome and also
with age. For example, in Angelman syndrome seizures are present in infancy
but become less frequent with the passage of time. In Rett syndrome, epilepsy
is severe in early childhood, but reduces with increasing age and may have ceased
by the time affected individuals reach their 20s. For a number of syndromes,
the presence of epilepsy can be a diagnostic marker: children with Aicardi and
Angelman syndromes have diagnostically distinctive ECG patterns, although less
markedly so after puberty.
Epilepsy can be an underlying cause of behavioural disturbance in individuals
with a behavioural phenotype. The use of electrophysiological measures in addition
to standard behavioural measures can help determine the impact of epilepsy on
an individual's behaviour. Routine screening of epilepsy should be performed,
particularly in the presence of deteriorating adaptive functioning. Intervention
techniques include the use of anticonvulsants to manage and control epilepsy.
Surgical intervention may also be considered in some instances, for example
in tuberous sclerosis when brain or renal tubers may require removal.
The course of behavioural phenotypes
Behavioural phenotypes associated with a progressive course
Some syndromes have a progressive course, whereas in others such as phenylketonuria
(PKU) and galactosaemia, progression of the syndrome is determined by dietary
management and elimination from the diet of phenylalanine and lactose respectively,
in order to prevent medical and adaptive deterioration. Clinicians should be
aware of the nutritional implications of implementing elimination diets, and
ensure that essential nutrients lost are substituted with dietary supplements.
This can prevent secondary complications such as osteoporosis. These remedial
progressive syndromes in addition to progressive and non-progressive syndromes
are listed in Figure 3.
At present, there are no cures for many of these progressive degenerative syndromes,
but it is important that practitioners are able to anticipate, recognize and
treat medical complications at an early stage, in order to increase quality
of life and life expectancy. Treatment should be multidisciplinary, incorporating
surgery, pharmacotherapy, physiotherapy and the use of mobility aids, and should
be aimed at managing symptoms and medical complications, as the following examples
show.
Emotional and practical support should be offered to both the individual and their family because of the shortened life expectancy of affected individuals, and genetic counselling should be offered to prospective parents. Short-term respite care is also beneficial for families.
Changes in the presentation of behavioural phenotypes with age
Ageing of individuals with behavioural phenotypes is an important issue for
clinicians. With recent advances in intervention and treatment techniques, this
population are living longer. It is therefore important that clinicians are
able to anticipate future medical complications.
The presentation of some of the key features of behavioural phenotypes can change
with age. The physical appearance of the individual can change, most notably:
The presentation of some of the key features may decline as the individual
ages; for example, in hypomelanosis of Ito the characteristic hypopigmentation
becomes less prominent in adulthood, and in neurofibromatosis type 1, café-au-lait
spots decrease after middle age (Barnard et al., 2002).
Carers and family members should be prepared for and fully informed of the course
of the syndrome, in order to anticipate any changes and alert medical professionals.
The observations of those closest to the individual are valuable in alerting
practitioners to any physical and behavioural changes.
Mortality and morbidity
The cause of mortality and morbidity in genetic syndromes in which behavioural
phenotypes occur is often complex. Associated medical complications and abnormalities
in conjunction with secondary complications have an interactive and complex
relationship. How they interact and how they are managed can impact on life
expectancy. In a number of syndromes, such as Cornelia de Lange, early intervention
and management of medical complications (e.g. cardiac anomalies, metabolic disorders
and severe obesity) can significantly extend longevity. Severity of phenotypic
expression can also determine mortality and morbidity. A number of the mucopolysaccharidoses
have both mild and severe phenotypic expressions, both of which can determine
life expectancy. Figure 4 shows
the typical life expectancy and the main cause of death for each syndrome.
Conclusion
Advances in clinical understanding of behavioural phenotypes and the mechanisms
that determine the syndrome, paralleled by advances in medical and therapeutic
interventions, have increased the quality of life for individuals with behavioural
phenotypes, and life expectancy has significantly improved. With increasing
age, secondary medical complications that are seen in the general population
are becoming more prevalent in this clinical population. Routine procedures,
such as regular screening for breast, cervical and prostate cancer, should be
offered. Clinicians should be aware that both the physical and behavioural profile
of many syndromes changes with age, and should prepare for this. The psychological
health of affected individuals should also be monitored throughout adulthood,
owing to the increased likelihood of developing psychiatric disorders.
REFERENCES AND FURTHER READING
Barnard L, Pearson J, Rippon L, O'Brien G. Behavioural phenotypes of genetic
syndromes: summaries including notes on management and therapy. In: O'Brien
G, ed. Behavioural Phenotypes in Clinical Practice. London: Mac Keith Press,
2002.
(Provides a comprehensive overview of the major syndromes, including management
and treatment interventions.)
Clarke D. Self-injurious and aggressive behaviour. In: O'Brien G, ed. Behavioural
Phenotypes in Clinical Practice. London: Mac Keith Press, 2002.
(An excellent overview of aberrant behaviours and management strategies.)
Gilbert P C. A-Z of Syndromes and Inherited Disorders. 3rd edition. Cheltenham:
Nelson Thornes, 2000.
(A good reference book that provides simple, straightforward information.)
Joyce T, Functional Analysis and Challenging Behaviour. PSYCHIATRY 2003; 2:8:
17-20.
O'Brien G, Pearson J, Berney T, Barnard L. Measuring behaviour in developmental
disability: a review of existing schedules. Developmental Medicine & Child
Neurology 2001; 43: Supplement 87: 1-70.
(Provides information of the most commonly used assessment schedules in learning
disability.)
O'Brien G, Barnard L, Pearson J, Rippon L. Physical health and clinical phenotypes.
In: Prasher V P, Janicki MP, eds. Physical Health of Adults with Intellectual
Disability. Oxford: Blackwell, 2002.
(Reviews the physical health issues implicated in behavioural phenotypes.)
Sarabatnam M, Fragile-X Syndrome. PSYCHIATRY 2003; 2:8:29-33.
Skuse D H. Behavioural phenotypes. PSYCHIATRY 2002;1:7: 98-102.
(A good, comprehensive introduction to the genetic mechanisms implicated in
behavioural phenotypes.)
| First published in Psychiatry; Volume 2:8 August 2003 and reprinted with the kind permission of The Medicine Publishing Company. |