Found on the net 4

TABLE 2.
Common Syndromes Associated with Mental Retardation
DIAGNOSIS INCIDENCE ETIOLOGY, INCLUDING INHERITANCE CLINICAL MANIFESTATIONS AND EARLY RECOGNITION ASSOCIATED CONDITIONS DIAGNOSTIC EVALUATION* PROGNOSIS SPECIAL CONSIDERATIONS
Down syndrome

1 in 600 to 800 births

Results from extra copy of chromosome 21, usually a sporadic event; 2% of cases may be inherited from a balanced translocation carrier parent

Hypotonia; flat facial profile; upslanting palpebral fissures; small ears; in-curving fifth fingers; single transverse palmar creases

Slow growth; congenital heart defect; thyroid dysfunction; developmental delay, especially speech

Chromosome analysis in all patients; chromosome analysis of parents if translocation is found; pediatric cardiology evaluation with echocardiogram by 6 weeks of age

Cognitive limitations, with most in mild to moderate MR range; decreased life expectancy can be associated with congenital heart defect, especially if not recognized in early infancy

Except in cases where parent has a translocation, risk for recurrence is 1%

Fetal alcohol syndrome

0.05 to 3 in 1,000 children diagnosed annually in United States

Alcohol consumption by mother during pregnancy

Diagnosis can be made at birth, based on history, baby's facial features (medial epicanthal folds, wide nasal bridge, small upturned nose, long philtrum, narrow or wide upper lip), low birth measurements

May include retardation, behavior problems, ADHD, seizures, autism

Good history and physical examination imperative; history of maternal drinking, pre- and postnatal growth retardation, dysmorphic facial features, CNS involvement; no laboratory tests available

Varies; growth may improve during adolescence and facial features may soften, but behaviors may cause serious problems

Many of these children are adopted; FAS and fetal alcohol effects (usually developmental and behavioral problems) are totally preventable

Fragile X syndrome

1 in 2,000 to 3,000 male live births; females may also be affected

Abnormality in FMR-1 gene located on X chromosome; inherited in X-linked manner so males are more severely affected

Macrocephaly; large ears; enlarged testicles after puberty; hyperextensible fingers

Autism/autistic- like behaviors; developmental delay, especially speech; clumsiness; mitral valve prolapse

DNA testing for fragile X mutation (chromosome testing for fragile X misses up to 7% of cases); mothers of affected boys are obligate carriers of the gene

Normal life expectancy; mild to profound MR

Females usually less severely affected than males; up to 50% of females with mutation have MR or educational difficulties; risk for recurrence is 50%

[ corrected] Velocardiofacial syndrome

1 in 700 live births

Deletion of chromosome 22; usually de novo but may be inherited in an autosomal dominant manner

Cleft palate; congenital heart defect; speech delay; elongated face with almond-shaped eyes; wide nose with hypoplastic alae nasi; small ears; slender, hyperextensible fingers

Learning disabilities ± mild MR; psychiatric disorder in 10%

High-resolution chromosome analysis with chromosome painting (FISH) to detect chromosome 22 deletion; parents should also be tested

Normal life expectancy unless severe heart defect (e.g., truncus arteriosus, interrupted aortic arch) is present

Risk for recurrence as high as 50%, depending on family history

Unknown cause of MR

30 to 50% of all cases of MR

Variable; diagnosis may evolve over time, so repeated evaluations may be helpful

Nonspecific cluster of minor malformations; delayed milestones, especially language development

Behavioral phenotype may also aid diagnosis as course evolves

Cytogenetic studies; brain imaging; metabolic studies

Will vary considerably based on etiology (if it can be established) and/or severity

Diagnostic techniques that may aid in diagnosis are constantly being refined

*— See Table 3 for summary of indications for diagnostic and screening tests.

MR = mental retardation; ADHD = attention-deficit/hyperactivity disorder; CNS = central nervous system; FAS = fetal alcohol syndrome; FISH = fluorescence in situ hybridization.

Information from references 4, 5, 7 and 18.

Evaluation and Referrals
Findings from the history and physical examination of the child will help determine which diagnostic tests and referrals are appropriate for further assessment. The physician needs to explain to the parents what these findings are and the reasons for further evaluation. The laboratory and radiographic assessment of individual children should be based on clinical presentation (Table 3).16

View/Print Table

TABLE 3.
Suggested Indications for Tests When Mental Retardation Is Unexplained
Magnetic resonance imaging of the brain

Cerebral palsy or motor asymmetry

Abnormal head size or shape

Craniofacial malformation

Loss or plateau of developmental skills

Multiple somatic anomalies

Neurocutaneous findings

Seizures

IQ < 50

Cytogenetic studies

Microcephaly

Multiple (even minor) somatic anomalies

Family history of mental retardation

Family history of fetal loss

IQ < 50

Skin pigment anomalies (mosaicism)

Suspected contiguous gene syndromes (e.g., Prader-Willi, Angelman, Smith-Magenis)

Metabolic studies

Episodic vomiting or lethargy

Poor growth

Seizures

Unusual body odors

Somatic evidence of storage disease

Loss or plateau of developmental skills

Movement disorder(choreoathetosis, dystonia, ataxia)

Sensory loss (especially retinal abnormality)

Acquired cutaneous disorders

IQ = intelligence quotient.

Adapted with permission from Palmer FB, Capute AJ. Mental retardation. Pediatr Rev 1994;15:476.

This initial sharing of information with parents is an extremely important step and will probably set the stage for the future physician-family-patient relationship. Ample time should be scheduled to discuss the findings and to allow for questions, which will be numerous. The family should be encouraged to write a list of questions for further communication with the physician. The clinician should clarify the term “developmental delay,” because parents frequently misinterpret this as meaning the child has the ability to catch up.

It is best to seek other opinions as soon as mental retardation is suspected rather than adopting a “wait-and-see” approach. The Individuals with Disabilities Education Act (1997)17 provides for developmental assessment of children older than three years in every school district. For children younger than three, similar infant-toddler assessment and early intervention resources are available, usually through local health departments, school districts or regional assessment centers. (The responsible agency varies in each state.)

Referral may be made to a tertiary-level child development unit that can provide interdisciplinary evaluations (developmental pediatrics, genetics, neurology, ophthalmology) as well as functional assessments (occupational and physical therapy, speech/language pathology, audiology, psychology). Families will usually welcome such a referral and comprehensive evaluation, especially if the mental retardation is unexplained. Evaluations by a nutritionist and a child psychiatrist may also be appropriate for some patients.

The family physician should expect complete information on the findings from this type of team evaluation. The family should expect to be referred back to their local community for ongoing primary care and, in some instances, subspecialty care. Information about early intervention resources in the local community should be shared with the family, and appropriate support services should be identified.

If the child with mental retardation has a head circumference that falls below the 5th percentile (microcephaly) or above the 95th percentile (macrocephaly), a magnetic resonance imaging scan of the brain should be considered. This is usually preferable to computed tomographic scanning because of the enhanced visualization of developmental abnormalities of the cerebral cortex, such as pachygyria, polymicrogyria and schizencephaly. These disorders reflect an abnormality during the first 25 weeks of gestation in the early migration of the neurons into the normally six-layered cortex.

A consultation with a medical geneticist/dysmorphologist is invaluable. This would include a review of a three-generation pedigree and records of pertinent relatives, evaluation for subtle dysmorphic features and assessment for a pattern to the patient's presenting characteristics.

Most mentally retarded patients who visit a genetics office undergo chromosome analysis. While this testing could be done by the referring physician, there are different levels of test quality, and it is usually best performed by a good cytogenetics laboratory associated with a university hospital or children's hospital. This allows for ease in interpretation of the results to the patient's family in the event an abnormality is found. DNA testing for fragile X syndrome should be done instead of cytogenetic testing, which can miss up to 7 percent of those who are affected.18 Metabolic testing in the absence of a history suggestive of metabolic disease is probably of little value.4

Diagnosis may require several periodic visits to a geneticist, because a phenotype may evolve slowly, and new syndromes are constantly being reported. The importance of making a diagnosis in a child with mental retardation cannot be overemphasized. An accurate diagnosis allows for anticipatory guidance for the patient, recurrence risk information and genetic counseling for the parents, and opportunities for the family to become involved in specific support groups. An uncertain diagnosis should be conveyed as such; no diagnosis is preferable to an incorrect one.

Within a given family, the risk of recurrence of mental retardation in future siblings or other relatives of the patient depends on the specific diagnosis. The recurrence risk for mental retardation cannot be given to the family until a diagnosis has been made, although a general discussion with a geneticist may be of benefit. The family physician is a valuable resource in periodically reviewing the recurrence risk for the family.

Practice guidelines for primary care of children with certain conditions (Down syndrome, fragile X syndrome) are also available,19–21 as are special somatic growth charts for some syndromes. There are also guidelines for the management of adults with mental retardation who have been deinstitutionalized.22 Table 4 lists Internet resources that may be valuable to the family physician.

View/Print Table

TABLE 4.
Internet and Computer Resources on Mental Retardation for Family Physicians
Syndrome Diagnosis, Pediatrics in Review, Multimedia Pages CD-ROM, Vol 18, No.11-CD, 11/97