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Pervasive Developmental Disorder: Childhood Disintegration Disorder

Updated: Nov 27, 2007

Introduction

Background

Childhood disintegrative disorder is a rare disorder, occurring in fewer than 5 in 10,000 children. It generally manifests by the fourth year of life, after a period of at least 2 years of normal development. Childhood disintegrative disorder manifests with a loss of previously acquired language and social skills and results in persistent delay in these areas. For example, a child previously able to speak in 2- or 3-word phrases gradually or abruptly loses the ability to communicate using words or uses only fragments. Social and emotional development also regress, resulting in impaired ability to relate with others. For example, a child previously able to accept reassurance from his or her parent (eg, a hug) loses the ability to be consoled and even may withdraw from human (tactile) contact.

Overall, the social, communicative, and behavioral features of childhood disintegrative disorder resemble those of autistic disorder. Distinct qualitative impairments in social interaction and communication are present. In addition, restricted, repetitive, or stereotyped patterns of behavior, interests, and activities occur. Motor loss of previously acquired skills (eg, child previously toilet trained soils during the day and night, child previously able to pedal a tricycle or draw shapes can no longer do so) is present. Additional symptoms may include the onset of difficulty in the transition of waking from sleep. Social interactions become compromised (eg, aggressiveness, tantrums, withdrawal from peers), as does motor function, resulting in poor coordination and possible awkwardness of gait.

Pathophysiology

No clear-cut pathophysiology is proven to cause this disorder; debate within the developmental disabilities field regarding long-term outcome of children with this disorder is noted. Some researchers hypothesize that predisposing genetic factors combined with environmental stressors (eg, prenatal or postnatal virus exposure, birth trauma) result in brain deposition of amyloid and disruption of synaptic transmissions, possibly involving interleukin-1 or beta-endorphins.

Frequency

United States

Frequency is very rare (<5 in 10,000 children). Childhood disintegrative disorder is much less common than autistic disorder.

International

No current studies are large enough to determine international frequency.

Mortality/Morbidity

No mortality or morbidity is caused directly by childhood disintegrative disorder. Indirectly, an increased risk of mortality and morbidity may be present because of a comorbid medical condition, such as a neurodegenerative disorder. The clinician should be alert to the possibility of Landau-Kleffner syndrome (LKS).
LKS is a rare condition of unknown etiology that is more common in boys who generally present with more severe language impairment and later than those with childhood disintegrative disorder; LKS has a mean onset of 5.5 years. Determining the presence of this syndrome is important because it is generally associated with seizure disorder and may respond to treatment with anticonvulsants such as valproic acid or steroids, in some cases.

Sex

This disorder is slightly more common in males than in females.

Age

Childhood disintegrative disorder, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), occurs only after a period of at least 2 years of normal development, when the child is younger than 10 years.¹ Onset generally occurs in children aged 3-4 years and may be insidious or abrupt.

Clinical

History

Obtain a thorough history.
The child is developmentally normal prior to the age of onset. This is similar to Landau-Kleffner syndrome (LKS); however, in LKS, the onset tends to be later (eg, age 5.5 y), whereas, in childhood disintegrative disorder, the onset is usually by age 3-4 years.
Developmental delays in language, social, emotional, cognitive, or motor areas are not apparent to either the parent or pediatrician prior to the onset of the disorder.
Children diagnosed with childhood disintegrative disorder tend to have more long lasting abnormalities of auditory responsiveness and verbal communication than children with pervasive developmental disorder but not as severe as in LKS.

Physical

Perform a thorough physical examination.
Occasionally after diagnosis, mild neurologic abnormalities (eg, mild macrocephaly, microcephaly, motor incoordination) are detected upon neurologic examination.
Specific physical abnormalities are not diagnostic of this disorder.

Causes

No single causal factor for childhood disintegrative disorder is known. Current research emphasizes that a combination of genetic susceptibility and prenatal (or environmental) stress may explain the finding of higher-than-expected brain deposition of amyloid and disruption of synaptic transmission, possibly involving interleukin-1 or beta-endorphins.

Environmental risk factors
- Viral exposure (usually intrauterine transmission) - Toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (TORCH)
- Birth trauma
- Toxin exposure
- Prematurity
Genetic factors
- Possible susceptibility to chromosomal breakage or disruption
- Family history of autism or Asperger disorder
Associated disorders
- Autoimmune disorders
- Allergy or asthma

Differential Diagnoses

Toxicity, Mercury

Workup

Laboratory Studies

Laboratory studies
- CBC count
- Thyroid function testing
  - Triiodothyronine (T₃)
  - Thyroxine (T₄)
  - Thyroid stimulating hormone (TSH)
- Glucose testing
- Liver function tests (gamma-glutamyltransferase)
- Kidney function tests
- Heavy metal screening
- HIV test
- Urine for aminoacidopathy screening
Psychological tests
- Children's Autism Rating Scale (CARS) - Yields information on the probability that the child's behavior pattern resembles that of children of commensurate developmental age who are autisticlike
- Kaufman Assessment Battery for Children (KABC) - Yields information on mental processing, sequential processing, and an intelligence quotient (IQ) equivalent composite score
- Vineland Adaptive Behavior Scale - Yields information regarding the child's level of adaptive functioning; has limitations, including reliability of the informants (eg, parents, caregivers)
Chromosome analysis to exclude coexisting genetic syndromes
Occupational therapy evaluation to determine presence of tactile sensitivity (eg, intolerant of hugs, uncomfortable with sensory input on skin) and to assess motor delays; Grandin hug box used by some occupational therapists
Educational and achievement testing to determine academic level and appropriate educational setting

Imaging Studies

MRI, positron emission tomography (PET), or CT scanning to exclude brain tumors or obstructive abnormalities in the brain parenchyma

Other Tests

Careful screening of the cranial nerves and a funduscopic examination
EEG as part of the neurologic workup to exclude seizure disorders (eg, Landau-Kleffner syndrome)
- Obtain both sleep (with nasopharyngeal leads) and awake EEGs.
- To exclude seizure disorder, 24-hour EEG is the most sensitive.

Treatment

Medical Care

The principles of treatment for the child with disintegrative disorder are generally supportive in nature and are focused on specific behavioral interventions. Perform interventions to halt behavioral deterioration as soon as possible and to improve the child's level of communication skills, self-help skills, social skills, and reality testing to stabilize general global functioning. Children who present with marked impairment of attention may improve with very low-dose (and carefully monitored) treatment with stimulants or nonstimulants (atomoxetine).

Consultations

Neurologist
- Neurologic consultation is extremely important to exclude neurologic conditions, which, if present, may be reversible.
- The neurology consult should include EEG (and sleep EEG), MRI, or PET (see Imaging Studies and Other Tests).
Child psychiatrist or behavioral and/or developmental pediatrician
- Advise consultations with these health professionals in conjunction with the pediatrician, family, and/or caregivers to assist with appropriate educational placement, therapeutic interventions, psychopharmacologic interventions, and psychotherapeutic interventions.
- Consider specific family support therapy for each individual with childhood disintegrative disorder.
Speech therapist: Arrange for a speech pathology consultation, especially if language delay is significant (delay of 25% or more).
Childhood intervention specialist: Collaboration of the primary clinician with an early childhood intervention specialist may facilitate appropriate educational placement.

Diet

No special diet is known to improve the clinical course or prognosis.
Salicylate-free diets (ie, Feingold diets), diets low in yeast, or diets high in certain megavitamins or minerals (eg, zinc, magnesium, vitamin B-6, vitamin B-12, fatty acids) have not resulted in measurable and predictable improvements; however, some anecdotal reports have shown limited response in individual cases. If a parent wishes to try a special diet, obtaining a nutrition consultation before and after the special diet is tried is recommended to prevent or reverse diet-induced vitamin, mineral, or calorie changes. Particular attention should be placed to ensure adequate (but not excessive) caloric intake to prevent growth retardation.

Activity

No specific activity limitations are needed unless sufficient motor deterioration suggests activity restriction, which should be child-specific.

Medication

Medications that address the core symptoms of this disorder are not known. No specific medications can be recommended for this disorder.

Medications in various classes, including antipsychotics, stimulants, and selective serotonin reuptake inhibitors (SSRIs), have been used to treat a wide range of behavioral and mood problems that may occur in children with this disorder. If neuroleptic medications are used (eg, atypicals such as risperidone, haloperidol, molindone), neuroleptic malignant syndrome (NMS) is a significant risk. NMS is a potentially irreversible and life-threatening syndrome that manifests with fever, rigidity, rhabdomyolysis, altered mental status, and lethargy and may progress to coma and respiratory depression without treatment. The treatment for NMS includes immediate cessation of the neuroleptic medication and immediate consultation with an anesthetist for respiratory support and possible treatment with dantrolene. These agents are also associated with a potential risk of QTc prolongation.

If seizure control is an issue and Depakote or valproate are used along with atypical antipsychotics (especially risperidone), the patient should be closely monitored for abnormal levels of ammonia, which are generally accompanied by alterations in mental status (often nonspecific slowing) and abnormalities of liver function.

If atypical antipsychotics are used (eg, risperidone, quetiapine, ziprasidone, aripiprazole), ongoing monitoring should include screening for metabolic syndrome, new-onset diabetes, or diabetic ketoacidosis both by physical examination (including waist circumference, blood pressure, weight out of proportion to height) and laboratory studies such as serum glucose and when indicated hemoglobin H1C.

Laboratory studies for NMS include creatine phosphokinase, lactic dehydrogenase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, BUN, and creatinine level tests.

Follow-up

Further Inpatient Care

Generally, inpatient care is not needed unless one of the following are present:

An associated medical condition (eg, seizures, head injury)
A severe psychiatric problem (eg, behavioral disturbances that warrant closer observation, supervision, and/or stabilization)
NMS
Alteration of electrolytes levels (such as hyponatremia related to treatment with SSRIs or atypical antipsychotics), which may need to be treated with intravenous therapy

Prognosis

Prognosis is guarded.
Children with moderate-to-severe mental retardation or lack of communicative language have a worse prognosis than those with usual IQ and communicative language.
The disorder is lifelong, and the social, communicative, and behavioral difficulties tend to impair function throughout life.
Risk of seizures increases with age and peaks at adolescence. Concomitant administration of SSRIs (eg, fluoxetine) and low-dose high-potency neuroleptics (eg, haloperidol) tends to lower the seizure threshold (as does alcohol), which may increase the likelihood of seizures.

Patient Education

Educating the patient, family, and/or caregivers is important so that an understanding of the nature of this disorder and its natural history is known.

Miscellaneous

Medicolegal Pitfalls

Failure to document language and developmental dysfunction in the child with head trauma at time of presentation is a medicolegal pitfall. For example, a 3-year-old child with a history of normal development exhibits a regression of language usage and development subsequent to a documented head trauma. Because ascertaining whether a loss of language and subsequent poor language development is directly related to the trauma may be difficult, documenting the child's condition at the time the child presents is important. This may include obtaining a comprehensive neurologic examination along with imaging studies. Documenting the child's current condition is important so that potential sequelae, such as seizures, can be excluded or diagnosed as present right after the trauma occurred. Documenting a reasonable cause for language dysfunction protects against potential liability.
Failure to notify child protective services regarding suspicion of abuse and safety issues regarding the presenting child is a medicolegal pitfall. For example, a child presents with a history of regression in social relatedness that occurs simultaneously with possible physical abuse by a parent. The physician is required legally to involve the local child protective service agency to investigate the suspicion of abuse and make a judgment regarding the child's safety. If this report is not made, the physician may be criminally liable. Call the child protective service agency regardless of whether the possible abuse is a likely cause of the child's problems with social relatedness.

References

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Keywords

childhood disintegrative disorder, Heller syndrome, dementia infantilis, disintegrative psychosis, language loss, loss of social skills, social development regression, emotional development regression, neuroleptic malignant syndrome, NMS, loss of motor skills, autistic disorder, autism, tantrums, Landau-Kleffner syndrome, LKS, seizure disorder, pervasive developmental disorder, birth trauma, Asperger disorder, asthma

Contributor Information and Disclosures

Author

Bettina E Bernstein, DO, Assistant Professor, Department of Psychiatry, Philadelphia College of Osteopathic Medicine; Attending Staff, Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia; Private Practice at the Wynnewood House, Consultant to Child Guidance Resource Centers
Bettina E Bernstein, DO is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry and American Psychiatric Association
Disclosure: Nothing to disclose.

Medical Editor

Carol Diane Berkowitz, MD, Executive Vice Chair, Department of Pediatrics, Professor, Harbor-University of California at Los Angeles Medical Center
Carol Diane Berkowitz, MD is a member of the following medical societies: Alpha Omega Alpha, Ambulatory Pediatric Association, American Academy of Pediatrics, American College of Emergency Physicians, American Medical Association, American Pediatric Society, and North American Society for Pediatric and Adolescent Gynecology
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation

Managing Editor

Caroly Pataki, MD, Professor of Clinical Psychiatry, Department of Psychiatry and Biobehavioral Sciences, Division Chair of Child and Adolescent Psychiatry, Director of Training, Child and Adolescent Psychiatry Residency Program, University of Southern California Keck School of Medicine
Caroly Pataki, MD is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, New York Academy of Sciences, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Nothing to disclose.

Chief Editor

Further Reading