CHAPTER 47 DOWN SYNDROME WILLIAM I. COHEN, MD Down syndrome (DS) is the most commonly occurring genetic disorder associated with mental retardation. Its physical characteristics are distinctive enough that health care providers who have early contact with the newborn— including obstetricians, delivery room and maternity nurses, and primary care physicians—can recognize the disorder relatively easily. This offers the advantage of early identification and treatment of associated serious and potentially life-threatening congenital abnormalities. Nevertheless, families often struggle with the fact they have not had the developmentally typical child they expected. Physicians should be mindful of the significant difference in perspective between health professionals and educators caring for children with DS and these children’s parents. As health professionals, we are educated in a deficit or pathological model (discovering and defining what is wrong with the child). Consequently, we often come in conflict with parents who recognize the value and potential of their child, celebrating their child’s achievements and abilities measured against his or her own previous attainment, rather than against a community or general standard. This pride in their child’s accomplishments has been augmented by the conscious decision to include these children in the life of the family and, more importantly, the community. In response to the efforts of families, the educational community has begun to appreciate the value of integrated education in preparing young people with DS to live and work in their communities. These changes have accelerated since the closing of public residential institutions, which began 20 to 30 years ago. Previously, infants and babies were removed from their homes and communities when wellintentioned individuals thought that raising a child with a disability at home would be too burdensome. Recent experience has shown how well these children thrive when raised in a personalized, loving environment. Background In 1865, the British physician John Langdon Down described a group of individuals who were residents of the Earlswood Asylum for Idiots in Surrey, England, where he was superintendent. These individuals with mental retarCurrent Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc dation had a particular facial appearance and resembled each other. Although they shared many characteristics in common, the biologic basis for this disorder remained unknown until 1959, when Jerome LeJeune determined that all the individuals with these characteristics had a third copy of chromosome 21. The phenotype of DS was found, in 95% of individuals, to represent the genotype of trisomy 21. Trisomies, in general, result from nondisjunction during the first meiotic division, and although they can occur in either parent, 95% of the extra chromosome 21 are of maternal origin. There is a well-documented agerelated increase in nondisjunction, which has been described as reflecting the loss of particular proteins that play a role in the completion of meiosis I at the time of ovulation. Trisomy 21 is a sporadic, noninheritable event. Nevertheless, the empirically observed increased risk of having another child with trisomy 21 is reported to be 1:100, or approximately 10 times the base rate of 1:800 to 1,000 live births. Of babies with DS, 3 to 4% have a translocation (the long arm of chromosome 21 is attached to either chromosome 14 or chromosome 21, resulting in 14/21 or 21/21 translocation). Although two-thirds of these translocations occur at the time of recombination in meiosis, onethird of these children will have inherited this translocated chromosome from a parent. That parent is called a balanced carrier, because he or she has only two copies of chromosome 21. It is recommended that parents of children with translocation DS have chromosomal studies to be certain they are not carriers and at risk for having another child with DS in a subsequent pregnancy. Down Syndrome Pages 297–303 298 / The Office Visit: Developmental Delay A small percentage of individuals with DS have mosaicism. They have two different types of cells in their bodies: some with the normal number of chromosomes, some with an extra chromosome 21. It is usually thought that children with subtle facial features or with cognitive abilities close to or within the average range invariably have the mosaic form of DS. This has been shown to be incorrect. The degree of mental retardation and the presence or absence of congenital abnormalities or medical problems is related to the specific tissues in the body that contain the extra chromosome. Diagnosis The DS phenotype is varied but includes a commonly occurring constellation of features. Hypotonia is most common and, along with characteristic facial features, often suggests the diagnosis in the newborn period. In fact, approximately 75% of all children with DS are identified by 6 months of age. Characteristic features include flat profile, epicanthal folds, upslanting palpebral fissures, depressed nasal bridge, brachycephaly (short anteroposterior measurement of the head), and short ears. Often, there is excess neck skin (nuchal fat pad). In addition, there is often a variety of diagnostic clues in the extremities: clinodactyly (shortened, curved fifth fingers), single palmar crease, wide gap between the toes, and plantar crease (Table 47-1). In any event, clinical suspicion of DS should lead to determination of the karyotype. When a physician suspects DS, parents often ask how certain they are of the diagnosis. In fact, most physicians have a high degree of certainty in the diagnosis when they order this test. However, it can be useful to express some uncertainty: “I think it’s likely, but we won’t know with certainty until we get the results back.” Families tell us that the possibility of a normal result can be helpful when waiting to find out if the child has DS. It allows them to begin to get used to the idea. After establishing the diagnosis of DS, the responsible physician has several other important duties: referral to genetics services, medical diagnostic services, developmental services, and family support. TABLE 47-1. Diagnostic Features of Down Syndrome Feature Upslanting palpebral fissures Wide gap between the toes Nuchal fat pad Depressed nasal bridge Brushfield’s spots Brachycephaly Epicanthal folds Clinodactyly Single palmar crease Percentage of Incidence (%) 98 95 87 83 75 75 60 50 50 Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc Genetics A consultation with a medical geneticist or genetics counselor can provide important information about the origin of DS (ie, the nature of nondisjunction) and the risk of having a subsequent child with DS. This is especially important for the child with translocation DS. Medical Diagnostic Services Babies with DS have an increased risk for various congenital malformations and appropriate diagnostic evaluations are warranted. Congenital cardiovascular abnormalities occur in approximately 50% of infants with DS, and the high frequency of atrioventricular septal defects, which frequently present without cardiac findings or symptoms, warrants a complete cardiologic evaluation. The high incidence of these abnormalities has led to the availability of screening echocardiography in some tertiary-care centers. DS is associated with a risk of hearing loss (sensorineural as well as conductive), and all infants should be evaluated with an objective measure of hearing, such as an auditory brainstem response test or transient evoked otoacoustic emission test as soon as the diagnosis is made. In hospitals that have instituted universal newborn hearing screening, the primary physician may often get the results of the screen at the same time the diagnosis of DS is considered. On the other hand, these screenings missed 14% of all infants (2003 data) and, therefore, the primary physician must be vigilant to be sure this test is performed. Gastrointestinal abnormalities occur more frequently in children with DS, and some of them, such as duodenal atresia and imperforate anus, are difficult to miss. On the other hand, Hirschsprung’s disease may present more subtly. An awareness of the increased frequency of this condition will lead to earlier diagnosis, which can be lifesaving. Hypothyroidism, both congenital and acquired, is a significant source of developmental morbidity for children with DS. Infants with DS have increased medical vulnerability in a number of areas, and physicians and families should monitor for these issues. For example, low muscle tone and poor coordination of suck and swallow can lead to feeding difficulties. Such difficulties warrant a referral to a feeding specialist, such as an occupational therapist or speech-language pathologist with expertise in treating oral-motor problems. Feeding difficulties may be further compounded by gastroesophageal reflux disease. Developmental Services All children with DS are eligible for early intervention (infant stimulation) services, which are provided for Down Syndrome Pages 297–303 Down Syndrome / 299 children from birth to 3 years of age by federally funded programs that are administered locally. (There are no outof-pocket costs to the family, and the services are provided in the family home.) Children are initially assessed and then receive various services appropriate to their ages and needs. These services include those of a developmental specialist and may include, at various times, physical, speech-language, and occupational therapies. Family Support Primary-care physicians aid parents by becoming knowledgeable about the kinds of family support available in the local community. Organizations such as Parent-toParent or the local Association for Retarded Citizens can provide information about support groups or one-to-one meetings with parents of children with similar medical and developmental problems. Most parents report that their contact with other families who have experienced similar problems is most useful in developing coping strategies. Your community may have a regional DS organization, affiliated with one of the national DS groups (see Practitioner and Patient Resources.) Medical Vulnerability Otolaryngologic Problems Ears, nose, and throat (ENT) problems are common in children with DS. Because of the characteristic midfacial hypoplasia, manifested as narrow airways, eustachian tubes, sinus ostia, and external auditory canals, children with DS are at increased risk for recurrent otitis media, nasopharyngitis or sinusitis, and the consequences of serous otitis media. This is of particular significance, given the well-known difficulties in expressive language development in children with DS. The medical team caring for the child must ensure his or her hearing is optimized to avoid the undesirable consequence of suboptimal language development. Children with DS have frequent episodes of croup, and this may reflect silent reflux causing upper airway irritation. These children may require laryngobronchoscopy to make the diagnosis. There is growing evidence of a wide variety of sleep abnormalities in children and adults with DS, and clinicians should consider an evaluation by a sleep center if symptoms are present. Anatomic features contribute to an increased incidence of obstructive sleep apnea. Even normally sized tonsils and adenoids may lead to relative obstruction, and adenoidectomy or tonsillectomy may be indicated in the presence of obvious symptoms. However, children with DS often are restless sleepers, awakening or at least arousing several times during the night. Some Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc youngsters sleep sitting up and leaning forward. It is unclear whether this represents undetected airway obstruction without apnea (related to the collapse of the airway and the arousal of the child in response) or a separate, central phenomenon. In addition, the base of the tongue may fall backward and play a role in airway obstruction. Recently, radiofrequency ablation has been used to treat this condition. Ophthalmologic Conditions Children with DS have an increased risk of cataracts. All infants should be evaluated at birth to detect the presence of dense congenital cataracts, which need to be removed immediately to prevent visual loss. The midfacial hypoplasia, described above, often leads to nasolacrimal duct stenosis. This can be treated conservatively, although surgical intervention is occasionally required. An increased incidence of refractive errors in children with DS and strabismus is common. Adolescents and adults are at risk for keratoconus. Endocrine Abnormalities The most common endocrine disorder for individuals with DS is hypothyroidism. This starts with the small but significantly increased risk of congenital hypothyroidism, which is 27 times more likely than in an infant without DS. In childhood and adolescence, hypothyroidism occurs frequently. A recently published longitudinal study from Sweden found that 35% of the patients followed monitored this disorder, one-half before the age of 8 years (Karlsson et al, 1998). After age 8 years, autoimmune thyroiditis is common. Yearly screening (thyroid-stimulating hormone [TSH] and free T4) is recommended to detect this condition, which may easily go unrecognized. Hematologic Problems DS is the most common factor predisposing to childhood leukemia: approximately 1% of children with DS develop one of four kinds of this disorder. This is 10 to 20 times the frequency observed in typically developing children (Lange, 2000). Ten percent of infants present with a transient myeloproliferative disorder in the newborn period (leukemoid reaction), which is characterized by a high white blood count and circulating megakaryoblasts. Most of these children recover without problems, although 25% will develop frank leukemia by age 4 years. Most children under 4 years of age who have DS develop nonlymphocytic leukemias, which appear to be extremely responsive to chemotherapy. In one series of 33 patients, all achieved a complete remission, and the group had an 80% estimated 8-year survival rate. Gastroenterology Celiac disease is reported to occur in 7 to 14% of individuals with DS. In addition to the usual symptoms of bloat- Down Syndrome Pages 297–303 300 / The Office Visit: Developmental Delay ing, diarrhea, and failure to thrive, children with DS may be asymptomatic, have constipation, or present with behavioral abnormalities. Periodic screening is recommended starting at 2 to 3 years of age, looking especially for immunoglobulin A (IgA) antiendomysial antibodies or elevated tissue transglutaminase levels. Serum IgA levels must be determined concurrently to appropriately interpret these screening tests. Currently, repeat screenings are suggested every 2 years. Recent genetics studies have linked celiac disease in DS to specific HLA-DQ alleles. One study suggests a two-stage screening, which would eliminate 70% of those who do not carry these alleles, and then rescreening the remaining 30% every 2 to 3 years (Czismadia et al, 2000). Gastroesophageal reflux occurs commonly in babies with DS, especially those with cardiac disease. The primary physician should be mindful for occult reflux and aspiration, which may present as croup or recurrent pneumonia. subject to manipulation of the neck (Cohen, 1998). This has led to the recommendation of universal precautions in administering anesthesia to children with DS, especially for ENT procedures. The presence of signs or symptoms warrants further neuroradiologic evaluation (magnetic resonance imaging). Symptomatic individuals must be referred for neurosurgical evaluation and treatment, which consists of fusion of C1 and C2. Current recommendations for screening include lateral cervical spine films (flexion, extension, and neutral) and measurement of the neural canal width between 3 and 5 years of age. (The neural canal width should be > 14 mm.) Participants in Special Olympics may need to have more frequent studies. It should be noted that adults with DS are at greater risk for cervical spine abnormalities, as a result of anatomic predisposition as well as the early onset of arthritic changes. Autoimmune Disorders Neurologic Disorders The increased incidence of autoimmune disorders leads to a higher incidence of both hypo- and hyperthyroidism (2% in a Swedish longitudinal study), celiac disease, juvenile-onset diabetes mellitus, juvenile rheumatoid arthritis, and alopecia areata. Musculoskeletal Disorders Ligamentous laxity is a common finding in children with DS. These children exhibit hypotonia and appear floppy and flexible. It is quite rare to see congenitally dislocated hips in children with DS, although hip problems do occur in adolescence. Adolescents also are prone to patellar dislocation. The most potentially serious problems caused by ligamentous laxity are related to the occiput and cervical spine. Laxity of the transverse ligaments can lead to excessive movement of C1 and C2. A small percentage of individuals with DS (estimated at 2%) will develop spinal cord compression from this excess movement. Approximately 13% of individuals with DS have > 4.5 mm distance between the atlas and the dens on lateral cervical spine radiographs when comparing full flexion and full extension. These individuals have been described as having “atlantoaxial instability” (AAI) and have been, in the past, considered at risk for the development of spinal cord compression. The belief that AAI was an asymptomatic precursor of cord compression, as well as the desire to prevent any possible injury, led to the recommendation that all individuals participating in Special Olympics have such studies performed. However, recent reviews of the literature have suggested that such screening may not be necessary and that individuals who are at risk for such spinal cord catastrophes either have symptoms or signs, such as neck pain, gait disturbance, bladder or bowel problems, or hyperreflexia and abnormal Babinski’s sign, or have been Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc Epilepsy Although seizures occur more frequently in individuals with mental retardation than in the typical population, the frequency of seizures in individuals with DS ranges from 5 to 10%. One-half these seizures can be attributed to an underlying medical problem (such as cardiovascular disease, infection, trauma, perinatal problems, or, more rarely, moyamoya disease). Consequently, a full investigation is warranted. The other 50% are idiopathic. A recent retrospective study of 350 Israeli children and adolescents with DS (performed between 1985 and 1997) showed that 8% had epileptic seizures, 47% had partial seizures, 32% had infantile spasms, and 21% had generalized tonicclonic seizures. In this group, neurodevelopmental outcome of children with infantile spasms was poor, in spite of adequate seizure control (Goldberg-Stern et al, 2001). In other series, however, timely recognition of this disorder, along with rapid institution of treatment, correlated with better outcomes. Those who had a delay in beginning treatment and who had a long time until the spasms stopped had a lower developmental quotient and a higher incidence of autistic features (Eisermann et al, 2003). Vigabatrin, which is not currently available in the United States, has been associated with rapid cessation of spasms. Autistic Disorders These disorders are more prevalent in children and adults with DS. Whereas the incidence of autism in the general population is reported at 15 per 10,000 population, current evidence suggests that the prevalence in DS is approximately 5 to 10%. In addition to an early onset of symptoms, children with DS seem more likely to develop the socalled disintegrative form of autism, in which a child with Down Syndrome Pages 297–303 Down Syndrome / 301 adequate development of cognitive, language, and adaptive skills undergoes a dramatic regression with the emergence of typical autistic features. These children warrant a full investigation and should be considered for prolonged video electroencephalographic evaluation. Attention-Deficit Hyperactivity Disorder This common neuropsychiatric disorder occurs more frequently in children with DS (and mental retardation in general) than in typically developing children. However, these children respond well to current medical management with stimulant therapy. The standardized rating scales are reliable when used with children with DS. Alzheimer’s Disease (AD) Parents of newborn babies with DS have often heard about the association of DS with Alzheimer’s disease (AD), and although this is not a condition that appears in childhood, the question of the likelihood of it developing later may well arise. DS has been associated with premature aging. This has manifested in various ways, for example, early onset of presbyacusis (age-related hearing decline) and changes in skin tone (early wrinkling). A number of studies of institutionalized adults with DS had suggested a very high degree of dementia. Neuropathologic study of these individuals revealed the typical findings of neurofibrillary plaques and neuritic tangles, consistent with AD. The presence of the gene that codes for amyloid precursor protein (APP) on chromosome 21 lent further credence to the anticipation that three copies of this gene lead to an excess of APP and, therefore, AD. However, careful study of this issue has revealed that the incidence of true AD is much lower. The presence of these findings in the brain has not inevitably correlated with symptoms of AD. One of the greatest sources of confusion has been the uncritical attribution of a change in behavior to dementia. Many conditions, most of which are treatable, lead to behavior change in individuals with DS. The most common is depression, either endogenous or exogenous. Undetected hypothyroidism also can lead to depressive symptoms. Furthermore, care must be taken to distinguish normal, age-related decline in function from that seen in individuals with dementia. In a series of 148 adult patients referred to the Adult Down Syndrome Clinic at Lutheran General Hospital in Chicago to evaluate decline in function, only 11 of 148 met the criteria for progressive and nonreversible decline and deterioration and would, therefore, merit the diagnosis of AD (Chicoine et al, 1999). Complementary and Alternative Therapies Many parents learn about a variety of complementary and alternative therapies for children with DS, sometimes from Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc other parents, often through the Internet. These include nutritional interventions (such as multivitamin, mineral, and amino acid combinations) that are purported to enhance learning, improve muscle tone, and decrease medical complications. In addition, some parents may pursue chiropractic treatment, neural enhancers, facial plastic surgery, and other interventions they hope will improve the lives of their children. Attempts to scientifically document the benefits claimed have been unsuccessful. (More information about this topic is available at <http://www.dshealth.com>.) The great interest in these treatments reflects parental hopes that their child might be spared the consequences of the cognitive disabilities so often associated with DS. Cooley has provided a compassionate guide for discussing these issues with parents. Developmental and Educational Issues DS is associated with mild to moderate mental retardation. A number of individuals are more capable, functioning in the normal range of cognitive abilities. Whereas most adults with DS require some supervision in their living and work environments, a small but increasing number of young adults live independently. Many of them are employed as self-advocates for themselves and others with developmental disabilities. Speech and Language Needs An important part of the developmental profile of individuals with DS is the greater delay in expressive language function than in cognitive abilities and receptive language. “When will my child start talking?” is the most common question asked by parents of young children. The problem appears to relate to difficulty in phonologic mapping. Speech-language clinicians encourage the use of total communication with young children with DS, including instruction in sign language, as a bridge to effective communication while working on verbal communication as well. Children with DS have strong visual skills, and this has been used to teach reading, which, in turn, has improved language skills. Unlike other conditions with language disabilities, adolescents and adults with DS can continue to develop verbal language, and they should be afforded the opportunity to receive appropriate services in this area. For those individuals who do not develop functional expressive language, augmentative communication devices are indicated. Education The Individuals with Disabilities Education Act (IDEA) is a federal law that provides funds for special education for individuals with disabilities. In addition to funding early interventions services for children from birth to 3 years of age, IDEA mandates that the educational system (local Down Syndrome Pages 297–303 302 / The Office Visit: Developmental Delay school district) take responsibility for providing for the developmental and educational needs of the child through his or her 21st birthday. Many children enter preschool programs for children with developmental disabilities where the same types of services provided by the early intervention system in the home are available. Some parents also enroll their children in preschool programs for typically developing children, recognizing the benefit of exposure to typically developing children. Traditionally, most children with special needs have been served in categorical programs and segregated environments. Children who were not successful in regular classroom situations were often pulled out for services, which were delivered in resource rooms for children or self-contained classes for children with learning disabilities or mental retardation. Recently, families have become aware of the value of educating their children alongside peers, in so-called “inclusive” settings. The services that the child may need are then provided in the regular classroom. These practices have several advantages. They help the child to generalize information across settings and they allow educators to incorporate physical therapy, occupational therapy, and speech-language strategies throughout the school day. One warning: inclusive education should be a choice that parents make. Well-intentioned friends, educators, or physicians should not impose this on the family, because in education, as in the rest of life, “one size does not fit all.” Parents should be aware of all methods of educating children with special needs and should have the option of choosing the program in their school district that best meets their child’s needs. Health Care Guidelines The frequency of detectable and preventable medical conditions has led to the development of various screening protocols for infants, children, and adults with DS. “Health Care Guidelines for Individuals with Down Syndrome” is currently available in a 1999 revision. It lists recommended laboratory tests and medical consultations by age. The current version was compiled by the Down Syndrome Medical Interest Group (United States) and developed in conjunction with the Committee on Genetics of the American Academy of Pediatrics, whose most recent revision of “Health Guidelines for Children with Down Syndrome” was published in Pediatrics in 2001. Although not identical, these documents are in general agreement. (Note: These protocols are designed to supplement, not replace, the standard well-child care protocols of the American Academy of Pediatrics and the American Academy of Family Physicians.) An updated version is expected in early 2005. Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc What follows is a brief summary of screenings and consultations recommended for the optimal care of the child with DS: Birth • Cardiac evaluation (should include echocardiogram) • Objective hearing evaluation (auditory brainstem response test) • Ophthalmoscopic exam to detect dense congenital cataracts • Thyroid function testing (check state-mandated screening) • Referral for early intervention • Discussion regarding availability of family support • Medical genetics consultation, as indicated, regarding discussion of future risk in subsequent pregnancies. The parents of any child with translocation genotype must have a karyotype to be certain they are not balanced carriers. First year of life • Periodic hearing evaluation (every 6 months) until pure tone audiograms can be performed, then yearly. • Eye examination by pediatric vision specialist by 6 months • Thyroid function testing (TSH and free T4) at 6 and 12 months Ages 1 to 12 years • • • • Continued periodic hearing evaluations Continued eye examinations Yearly thyroid function testing Screening for celiac disease (beginning at 2 to 3 years of age), repeated every 2 years • Lateral cervical spine radiography (flexion, neutral, and extension), measuring the atlanto-dens interval and the neural canal width, between 3 to 5 years of age, looking for atlantoaxial instability Adolescence • Continued yearly thyroid function testing • Continued periodic vision and hearing assessment • Adolescent medicine consultation regarding sexual health concerns • Educational programming with a focus on transition planning Families currently obtain large amounts of information about DS from a variety of sources. Shortly after the birth of the baby (or after prenatal diagnosis), community-based parent groups (often in partnership with clinical programs providing consultative medical care to individuals with DS) can provide the family with extensive information about Down Syndrome Pages 297–303 Down Syndrome / 303 DS. Examples of materials provided include books on health and development, videos describing typical reactions to the unexpected birth of a baby with DS, information regarding parent support meetings, pamphlets on breastfeeding, and information on accessing developmental services. The Internet is often accessed as a source of information about DS, though the reliability of that information can vary. The primary care physician should anticipate that the family will be knowledgeable and often is looking to partner and collaborate with the physician. When based on trust and mutual respect, this collaboration can provide enormous satisfaction to all, focusing on optimal medical, developmental, and emotional outcomes. Suggested Readings Chicoine B, McGuire D, Rubin S. Adults with Down syndrome: specialty clinic perspectives. In: Janicki MP, Dalton AJ, editors. Dementia, aging and intellectual disabilities: a handbook. Portland (OR): Taylor and Francis; 1999. Cohen WI. Atlantoaxial instability. What’s next? Arch Pediatr Adolesc Med 1998;152:119–22. Lange B. The management of neoplastic disorders of haematopoiesis in children with Down’s syndrome. Br J Haematol 2000;110:512–24. Pueschel SM, Pueschel JK. Biomedical concerns in persons with Down syndrome. Baltimore (MD): Paul Brookes; 1992. Practitioner and Patient Resources Stray-Gundersen K. Babies with Down syndrome. 2nd ed. Bethesda (MD): Woodbine House; 1995. Van Dyke DC, Mattheis P, Eberly SS, et al, editors. Medical and surgical care for children with Down syndrome: a guide for parents. Bethesda (MD): Woodbine House; 1995. Down Syndrome: Health Issues http://www.ds-health.com This is the most comprehensive DS site on the Internet. Developed by Dr Len Leshin, a pediatrician who has a son with DS, it features a comprehensive listing of medical, scientific, and practical information about DS, as well as DS organizations and clinics worldwide. It lists contact information for many local and state or provincial parent groups providing family support. Cohen WI, editor. Health care guidelines for individuals with Down syndrome: 1999 revision. Down Syndrome Quarterly 1999;4:1–15. Down Syndrome Quarterly http://www.denison.edu./dsq Cooley WC. Nonconventional therapies for Down syndrome: a review and framework for decision making. In: Cohen WI, Nadel L, Madnick ME, eds. Down syndrome: visions for the 21st century. New York: Wiley-Liss; 2002. Down Syndrome Quarterly is an interdisciplinary journal devoted to advancing the state of knowledge on DS and covers all areas of medical, behavioral, and social scientific research. The 1999 “Health Care Guidelines for Individuals with Down Syndrome” are available online at <http://www.denison.edu/collaborations/dsq/health99.html> Csizmadia CG, Mearin ML, Oren A, et al. Accuracy and costeffectiveness of a new strategy to screen for celiac disease in children with Down syndrome. J Pediatr 2000;137:756–61. Eisermann MM, DeLaRaillere A, Dellatolas G, et al. Infantile spasms in Down syndrome—effects of delayed anticonvulsive treatment. Epilepsy Res 2003;55:21–7. Goldberg-Stern H, Strawsburg RH, Patterson B, et al. Seizure frequency and characteristics in children with Down syndrome. Brain Dev 2001;23:375–8. Karlsson B, Gustafsson J, Hedov G, et al. Thyroid dysfunction in Down’s syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 1998;79:242–5. Current Management in Child Neurology, Third Edition © 2005 Bernard L. Maria, All Rights Reserved BC Decker Inc National Down Syndrome Society http://www.ndss.org The mission of the National Down Syndrome Society is to benefit people with DS and their families through national leadership in education, research, and advocacy. National Down Syndrome Congress (NDSC) http://www.ndsccenter.org The purpose of the NDSC is to promote the interests of persons with DS and their families through advocacy, public awareness, and information dissemination on all aspects of DS. Down Syndrome Pages 297–303