American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 145C:232– 240 (2007) A R T I C L E Analysis of 88 Adult Patients Referred for Genetics Evaluation STEPHANIE N. MAVES, MARC S. WILLIAMS,* JANET L. WILLIAMS, PETER J. LEVONIAN, AND KEVIN D. JOSEPHSON We present a series of 88 adult patients referred for diagnostic genetic services in two settings. Patients referred for prenatal diagnosis, adult-onset neurodegenerative disease or cancer susceptibility counseling were specifically excluded from analysis. Information was obtained regarding age, gender, referral sources, previous genetics evaluation, referring diagnosis, final diagnosis, diagnostic test, and recommendations. The patients were able to be grouped into seven general categories: multiple congenital anomalies with or without mental retardation (26 patients), collagen-connective tissue disorders (18 patients), mental retardation (12 patients), chromosomal abnormalities (12 patients), bone growth disorders (6 patients), endocrine/metabolic (8 patients), and miscellaneous (6 patients). Patients and referring providers were not surveyed regarding utility of the evaluation. However, genetics notes were reviewed on all patients and potential benefits of the evaluation were identified. All patients had at least one potential benefit, with the majority having several. This study represents one of the largest published groups of non-institutionalized adult patients that have undergone comprehensive genetic evaluation. The role of the clinical geneticist as a member of the health care team in this population will be discussed. ß 2007 Wiley-Liss, Inc. KEY WORDS: dysmorphology; care of adults; mental retardation; multiple congenital anomalies; diagnosis How to cite this article: Maves SN, Williams MS, Williams JL, Levonian PJ, Josephson KD. 2007. Analysis of 88 adult patients referred for genetics evaluation. Am J Med Genet Part C Semin Med Genet 145C:232–240. INTRODUCTION It has been suggested that clinical geneticists may have the appropriate training and expertise to partner with primary care physicians to provide care for adults with mental retardation [Baird et al., 1988]. A potential problem with this concept is that little is known about what types of patients might present as adults to a genetics clinic, outside of more traditional clients in It has been suggested that clinical geneticists may have the appropriate training and expertise to partner with primary care physicians to provide care for adults with mental retardation. A potential problem with this concept is that little is known about what types of patients might present as adults to a genetics clinic. prenatal, oncology and neurodegenerative diseases. To address this issue, we present a consecutive series of adult patients referred to two genetic clinics. MATERIALS AND METHODS Marc S. Williams, M.D., F.A.A.P., F.A.C.M.G. is the director of the Intermountain Healthcare Clinical Genetics Institute in Salt Lake City, Utah. Trained as a Pediatrician and Dysmorphologist, Dr. Williams has had additional experience as a medical director of a managed care organization. He has developed interests in the role of genetics in health care delivery and quality improvement in clinical genetics. He has published and presented extensively on this topic. In addition to administrative duties and program development, Dr. Williams runs a clinic for evaluation of adults with mental retardation, birth defects and genetic disorders. He was recently elected to the Board of the American College of Medical Genetics, having chaired the Committee on the Economics of Genetic Services for 5 years. In 2007, he was appointed to the Secretary’s Advisory Committee on Genetics, Health and Society as well as the Personalized Medicine workgroup of the Department of Health and Human Services’ American Health Informatic Communities. He heads the ACMG Special Interest Group on Quality Improvement and participates in the activities of the Adult Genetics Special Interest Group. He has authored over 20 articles in the peer-review medical literature, edited the ACMG Manual on Reimbursement for Medical Genetic Services and presented over 50 papers at national and international meetings. *Correspondence to: Marc S. Williams, Director Intermountain Healthcare, Clinical Genetics Institute, 324 10th Ave. Suite 130, Salt Lake City, UT 84103. E-mail: firstname.lastname@example.org DOI 10.1002/ajmg.c.30141 ß 2007 Wiley-Liss, Inc. Patients were identified through a search of the WISAR genetics database maintained at the University of Wisconsin at Madison and the Adult Genetics Clinic records at the Intermountain Healthcare Clinical Genetics Institute. The search identified only individuals over age 18 that had been seen by an author (MSW) and excluded prenatal and presymptomatic diagnoses, cancer, and other conditions not associated with mental retardation, dysmorphic features, malformations or apparent single gene inheritance. Patients who have been continually followed by genetics since ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c childhood were also excluded, leaving those whose first visit was after age 18 with the exception of a few who had been seen by genetics in the distant past, without follow-up. Allowing for the exclusions, both populations represent consecutive series of patients with complete ascertainment from the clinic populations. Charts were reviewed and a study population of 88 individuals was identified. Information on these individuals, including age, gender, previous genetics visit information, referring diagnosis, referring physician specialty and institution, age at first visit, visit dates, reason for referral, final diagnosis, diagnostic testing, living situation, and family history information was obtained. The patients were grouped into the following seven general categories: multiple congenital anomalies with or without mental retardation (MCA/MR), collagen-connective tissue (CT) disorders, isolated mental retardation (MR), chromosomal abnormalities, bone growth disorders, endocrine/metabolic, and miscellaneous. The MCA/MR designation was given when congenital anomalies were a dominant feature. Syndromes where mental retardation is the prominent feature, even if associated with minor anomalies (such as fragile X) were assigned to the isolated MR group. Similarly, assignment to the endocrine/ metabolic category was based on either the underlying pathogenesis of the disorder (as in Smith–Lemli–Opitz syndrome) or if an endocrinologic or metabolic feature was either the presenting complaint or a prominent and distinctive feature of the phenotype. All patients with chromosomal abnormalities were placed in the chromosomal anomaly group, even if the abnormality was not thought to be causative if another diagnosis was not apparent. Patients and referring providers were not surveyed regarding utility of the evaluation. However, genetics notes were reviewed on all patients and potential benefits of the evaluation were identified. RESULTS Seventy-one patients were ascertained through the WISAR database, and 17 were seen through the Intermountain Adult Genetics Clinic. Of the 88 individuals, 40 (45%) were female and 48 (55%) were male. There was a difference in the sex ratios from the two groups. The WISAR group was 59% male, while the Intermountain (IM) group was 35% male. The age range was 18–75 years with a mean of 31.7 years. The patients from WISAR database were slightly younger than the IM patients (30.4 vs. 36.9 years). Breakdown of the diagnostic categories by frequency and gender are detailed in Table I. The living situation of these individuals was as follows: 26 lived with a spouse or a partner (WISAR 23%, IM 59%), 20 lived with family (WISAR 20%, IM 35%), 13 lived by themselves (all WISAR), 11 individuals lived in group homes (all WISAR), 5 lived semi-independently (all WISAR), 5 lived with foster parents or caregivers 233 (WISAR 5%, IM 6%), 3 were institutionalized (all WISAR), and 1 lived with a guardian (WISAR). Four individuals had unknown living situations (all WISAR). An analysis of the diagnoses per diagnostic category was performed and diagnostic commonalities within each category were identified as follows. MCA/MR This is the largest category with 26 patients (21 WISAR, 5 IM). Within the MCA/MR diagnostic category, two individuals (a brother and sister) had a presumed autosomal dominant syndrome (parent refused to be evaluated). Likewise, two other sibs had a presumed autosomal recessive disorder. One individual each was diagnosed with the following: Marinesco–Sjogren syndrome, Norrie disease, hypohidrotic ectodermal dysplasia syndrome, ectrodactyly ectodermal dysplasia clefting (EEC) syndrome, Cornelia de Lange syndrome, tuberous sclerosis, Coffin– Lowry syndrome, and distal arthrogryposis type 5 with primary pulmonary hypertension. Fourteen individuals were undiagnosed or had a possible diagnosis that could not be confirmed clinically or with laboratory testing (examples include: Prader–Willi syndrome ruled out; possible Ruvalcaba–Myhre syndrome; possible Simpson–Golabi– Behmel syndrome; MCA with both encephalocele and intestinal malrotation; MCA and obsessive compulsive disorder; Down syndrome phenocopy; microcephaly, late-onset lymphedema, and borderline MR inconsistent with microcephaly–lymphedema syndrome). TABLE I. Number and Gender of Individuals Per Diagnostic Category Diagnostic category Bone growth Chromosomal Collagen-CT Endocrine/metabolic MCA/MR MR Miscellaneous Total Number (%) Male Female 6 (6.8) 12 (13.6) 18 (20.5) 8 (9) 26 (29.6) 12 (13.6) 6 (6.8) 88 (100) 3 7 11 5 15 6 1 48 3 5 7 3 11 6 5 40 Collagen-CT Eighteen patients were in this category (15 WISAR, 3 IM). Within the collagen-CT category, there were six individuals with an Ehlers–Danlos syndrome: five having the hypermobility type, and one whose type was undetermined. Another individual had collagen abnormalities resembling Ehlers– Danlos (vascular type) but had normal 234 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c collagen III studies. Two individuals presented with MASS phenotype. Other diagnoses (one individual each) were Stickler syndrome, annuloaortic ectasia (autosomal dominant), Marfan syndrome, and osteogenesis imperfecta Type I. Five individuals were not diagnosed with a specific syndrome— three with tall stature (one of whom also had scoliosis and one with familial disproportionate tall stature), one with cutis laxa and polydactyly, and one with an apparent autosomal dominant condition with osteoporosis and multiple fractures with normal Type I collagen studies. Chromosomal Abnormalities Twelve patients were in this category (11 WISAR, 1 IM). Three individuals had sex chromosome disorders (2 with 47, XYY and 1 with 47, XXX and a clinical diagnosis of distal arthrogryposis Type II E. High resolution chromosome analysis in this individual additionally revealed a deletion of chromosome 2q37.3. The limb anomalies were consistent with the Albright-like pattern seen in this chromosomal deletion, so the diagnosis of arthrogryposis Type II E was removed). Three individuals had a chromosome 22q11.2 deletion: two with clinical features of Shprintzen syndrome, and one with Opitz syndrome. Two patients had Down syndrome. There were two individuals with autosomal inversions: one with a de novo 18(q22.1q23) paracentric inversion that was thought to explain the clinical features, and one with a familial pericentric inversion of chromosome 4. One individual had the karyotype 46, XY del(6)(p22.2p25.2). An additional patient had a duplication or insertion 22q11.2 that was inherited from her normal mother. MR A total of 12 fell within this category (all WISAR). Ten individuals have not been diagnosed with a specific genetic syndrome (one may have a familial form of mental retardation and another possibly is affected with Kleine–Levin syndrome [Arnulf et al., 2005]). The remaining two individuals within this category have fragile X syndrome. Endocrine/Metabolic Eight patients were in this category (five WISAR, three IM). The following diagnoses were present in one individual each: Smith–Lemi–Opitz syndrome; phenylketonuria (PKU); mitochondrial myopathy with seizures and mental retardation; uncharacterized neurotransmitter disorder; pseudohypoparathyroidism (Type I A); hypogonadotropic hypogonadism with mental retardation (Kallman syndrome ruled out); hypergonadotropic hypogonadism; and an uncharacterized syndrome consisting of primary amenorrhea, tall stature, macrocephaly, and learning disabilities. Bone Growth Six patients were placed in this category (all WISAR). There were no common diagnoses within the bone growth category with one individual in the study population with each of the following diagnoses: achondroplasia; osteogenesis imperfecta (Type I) and achondroplasia (in the same individual); chondrodysplasia punctata (X-linked dominant); Klippel–Feil syndrome (Type II); metaphyseal dysplasia ARTICLE (unique); and bone dysplasia similar to Pyle dysplasia (autosomal dominant). Miscellaneous Six individuals were in this category (one WISAR, five IM). Each had a unique diagnosis. These included autosomal recessive spastic paraplegia, polycystic liver disease, chronic bronchitis (cystic fibrosis ruled out), autosomal recessive sensorineural hearing loss, cardiac conduction abnormality (long QT syndrome excluded), and cardiomyopathy with possible sensory neuropathy (Fabry carrier status excluded). There were a wide range of specialties referring these individuals. Table II shows the number of individuals referred by each specialty. Analysis was done to see how many individuals were given a diagnosis or had a diagnosis changed because of their genetics visit. Out of the 88 individuals in the study population, 53 (60%) had a provisional diagnosis before their visit. Twenty-seven of these previously diagnosed individuals had their diagnoses changed or refined. Table III shows the previous and final diagnosis of these individuals, clinical features and the diagnostic testing that has been done. Twenty of the 27 individuals that had their diagnosis changed, had their referring diagnosis excluded. Of note, all six patients referred with possible Marfan TABLE II. Referral Source and Number of Referrals Referral source Behavioral medicine/adult psychiatry Family practice Internal medicine Ob/Gyn Neurology Physical medicine Orthopedic surgery (Speech pathology, pulmonary, cardiology, ENT; ophthalmology, pediatrics, Med/Peds, endocrine; adult disabilities, neurosurgery, urology) Self/family Number of referrals 29 16 9 4 4 3 2 1 each 10 Familial tall stature Tall stature, Marfan syndrome ruled out Ehlers–Danlos, hypermobility type MASS phenotype Ehlers–Danlos Type III Annuloaortic ectasia (autosomal dominant) MCA Obsessive compulsive disorder/PWS ruled out Marinesco–Sjogren syndrome AD familial osteoporosis OI Type I Ectrodactyly ectodermal dysplasia clefting syndrome (EEC) Klippel–Feil, Type II MCA Chondrodysplasia punctata, X-linked dominant Marfan syndrome Possible Marfan syndrome Possible Marfan syndrome Possible Marfan syndrome Possible Marfan syndrome Cystic medial necrosis (aortic) Prader–Willi syndrome Prader–Willi syndrome Possible Prader–Willi syndrome Possible osteogenesis imperfecta Osteogenesis imperfecta, ? type Zlotogora–Ogur syndrome (recessive) Spina bifida occulta Encephalocele Conradi disease, Conradi– Hunermann syndrome Final diagnosis Tall stature Marfan syndrome Referring diagnosis Tall stature, mild disproportion, scoliosis, hyperextensibility (mild) Esotropia, tall (proportionate), long thin face, malar flattening, high arched palate Mildly disproportionate tall stature, mild hyperextensibility of joints Disproportionate short stature, rhizomelia, bone fragility Proportionate tall stature, joint hypermobility with dislocations, myopia, mitral valve regurgitation Hypermobility, chronic pain syndrome Aortic Aneurysm MR, short stature, hypotonia nystagmus, exotropia, left ptosis, moderate conductive hearing loss, occipital skull defect, mild cerebellar atrophy, short fingers and metatarsals Possible seizures, chronic rectal prolapse, synophrys, upslanting palpebral fissures Obesity, MR, primary hypogonadism, spinocerebellar ataxia, neuropathy and myopathy, congenital cataracts, seizures, microphthalmia Low bone density, multiple fractures, nl sclerae and hearing, no abnormal bleeding Low bone density, multiple fractures blue sclerae, mild bleeding problems, family history positive Thin hair, syndactyly, conjunctivitis secondary to decreased tears, decreased saliva, cleft lip and palate Butterfly vertebrae, vertebral fusion Intestinal malrotation, encephalocele (occipital), block fusion of C2-C5 (Klippel–Feil) Short stature, severe Kyphoscoliosis, microphthalmia, congenital cataracts, alopecia Clinical features None None None None None Normal Type I collagen analysis Muscle and nerve biopsy, chromosomes (nl), head CT (nl), FSH (elevated), EMG Chromosomes: 46, XY, negative fraX, head CT-nl Echocardiogram (nl) None Chromosomes, 15q methylation studies (nl) None Types I and III, collagen analysis (nl) None None Echocardiogram, ophthalmologic exam (nl) Tests TABLE III. Referring Diagnosis Followed by Final Diagnosis and Tests Done of Individuals Whose Diagnosis was Changed or Refined by Their Genetics Visit ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c 235 47,XXX del2q(37.3:ter) Albright-like osteodystrophy MCA 47,XXX; distal arthrogryposis Type II E Learning disability MCA Polycystic liver disease Chronic bronchitis Hypertrophic cardiomyopathy Distal arthrogryposis type 5 Cardiac conduction abnormality CNS neurotransmitter disorder Cerebral palsy von Hippel–Lindau Cystic fibrosis Fabry disease female carrier Distal arthrogryposis Possible long QT syndrome Autonomic neuropathy, paroxysmal kinesogenic dystonia Cockayne syndrome Autosomal dominant bone dysplasia similar to Pyle dysplasia MCA (autosomal recessive) Brachydactyly syndrome type E TABLE III. (Continued) LD, primary amenorrhea, tall stature, macrocephaly Microcephaly, late-onset lymphedema, borderline MR, cystic hygroma Multiple liver cysts, few kidney cysts, cerebral aneurysms Bronchitis and bronchiectasis Cardiomyopathy, possible peripheral neuropathy Joint contractures, characteristic stance, abnormal eye movements, pulmonary hypertension Electrolyte disturbance, hypokalemia, ataxia, neuropathy, intermittent paralysis Combination of types D and E brachydactyly, multiple metaphyseal abnormalities Hydrocephalus, short stature, scoliosis, blepharophimosis, microcorneae, conductive hearing loss, facial asymmetry, maxillary retrusion, thin nose with overhanging tip MR, short 4th metacarpals, metatarsals EKG after electrolytes normalized (nl) CSF neurotransmitter levels (abnl) multiple metabolic studies (nl) None Sweat chloride (nl) Fabry gene sequencing (nl) None Chromosomes, 22q FISH, FSH, LH, estradiol, prolactin Renal US, chromosomes, 22q FISH High resolution chromosomes Skeletal survey, calcium, phosphate and alkaline phosphatase, chromosomes (nl) Normal parathyroid and thyroid assessment, CT head-arrested hydrocephalus, normal skeletal survey 236 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ARTICLE syndrome were found not to have this condition. Eleven (41%) of the diagnoses were changed or refined based on clinical examination alone. Of the 35 undiagnosed individuals, 11 acquired a diagnosis. Table IV shows the individuals’ clinical features, their final diagnosis and testing done. The most common diagnoses involved chromosome anomalies and fragile X syndrome. Molecular diagnostic tests proved useful in several of the cases. Seventeen individuals had previously been seen by a geneticist. Nine of these individuals had been given their diagnosis at the first appointment, and three were given a definitive diagnosis upon return. Five remained without a specific diagnosis. Potential benefits for individuals within the study population were not formally assessed but were inferred from review of the clinic notes and patient letter. Possible benefits include: Possible benefits include: family testing, recurrence risk information, prenatal testing, symptom management, diagnosis specific preventive care (necessary, meaning a specific care plan was developed or unnecessary, meaning that specific care was discontinued given the change in diagnosis), adult anticipatory care, primary care referral (for those without an established primary care physician), specialty referral, and referral to organizations. family testing, recurrence risk information, prenatal testing, symptom management, diagnosis specific preventive care (necessary, meaning a specific care plan was developed or unnecessary, meaning that specific care was discontinued given ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c 237 TABLE IV. Final Diagnosis, Clinical Features and Tests Done of Those Diagnosed by Their Genetics Visit Final diagnosisa Pseudohypoparathyroidism Type I A Ehler-Danlos, hypermobility type Shprintzen syndrome, 46, XX, del(22)(q11.2)ish Shprintzen syndrome 46,XX,del(22)(q11.2)ish 46, XY, del(6)(p22.2p25.2) 47, XYY 47, XYY 46,XX,inv18 (q22.1q23) Fragile X syndrome Fragile X syndrome Hypogonadotropic hypogonadism a Clinical features Tests done Short stature, brachmetacarpalia, brachmetatarsalia Joint hypermobility with multiple dislocations, short clubbed distal phalanges, easy bruisability, smooth, velvety skin Characteristic facial appearance, velopharyngeal incompetence, anterior laryngeal web, short stature, MR MR, submucous cleft palate, myopia, mitral valve prolapse, unilateral renal agenesis, unusual facial features MR, ureteropelvic junction obstruction, hypotonia, anisometropic hyperopia, nystagmus Mild dysmorphic features, prominent jaw, increased testicular size, scoliosis, developmental delay, unusual hair pattern, long mandible, prominent ears Pervasive developmental disorder, left conductive hearing loss MR, small auditory canals, midface hypoplasia, congenital hip dislocation, motor disorder of speech, unusual sleep pattern, deep set eyes, upslanting palpebral fissures synophrys, alternating exotropia Macroorchidism, long thin face, MR n/a Spastic diplegia, short stature, borderline microcephaly, brachycephaly, malar flattening, mild prognathism, pectus carinatum, gynecomastia, first degree hypospadius, sm testes, decreased elbow extension, intact sense of smell, severe osteoporosis, osteomalacia PTH, phosphorous, 1,25 dihydroxy vitamin D (low), MRI of the brain Types I and III collagen analysis (nl) Chromosomes Chromosomes Chromosomes Chromosomes Chromosomes Chromosomes Chromosomes 46, Y fra(x)(q27.3) Chromosomes Chromosomes (nl), FSH and LH (low: 1.1 and 0.4), testosterone 15 (low), prolactin (6), estrogen (52), ACTH stimulation test (nl) Diagnosis does not necessarily explain presenting complaints. the change in diagnosis), adult anticipatory care, primary care referral (for those without an established primary care physician), specialty referral, and referral to organizations (these include social service agencies, generic advocacy groups, and syndrome-specific support groups). The average number of benefits per individual was 2.1. The breakdown is as follows: 27 individuals received one potential benefit, 25 individuals received two, 20 received three, 11 received four, and 5 individuals received five potential benefits. Breakdown of benefits by number receiving that benefit is shown in Table V. The number of benefits did not appear to vary significantly based on whether a diagnosis was made (formal statistical analysis not done). DISCUSSION There are several unique aspects of this study. Our study is one of the few having a strictly adult population. In addition, all but three individuals in the study population live in the community. Most surveys of adult genetic patients have focused on institutionalized adults [Haspeslagh et al., 1991; Butler and Singh, 1993; Van Buggenhout et al., 1999, 2001a,b]. These studies have less relevance at the present time, due to the move towards placement in the community. Institutionalized patients also increasingly represent only the most severe end of the disability spectrum and generally do not ascertain individuals without cognitive disability. There are 238 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c TABLE V. Breakdown of Benefits by Number of Individuals Benefit Referral to specialties Symptom management Recurrence risk Family testing Adult preventive care Diagnosis-specific preventive care Necessary Unnecessary Participation in research Prenatal testing Referral to organizations several population-based prevalence studies of adults with intellectual disability that included ascertainment of individuals living in the community [Hand, 1993; Hand and Reid, 1996; Janicki et al., 2002]. The referenced studies characterized health issues in these populations, but did not assess the etiology of the intellectual disability beyond identification of patients with Down syndrome, cerebral palsy, and ‘‘unspecified neurologic impairment’’ [Hand and Reid, 1996]. The latter two ‘‘diagnoses’’ are non-specific descriptors that are otherwise uninformative. In addition, these studies do not ascertain individuals with genetic disorders or significant congenital anomalies if they are not associated with intellectual disability. To our knowledge the present study is the only consecutive series of non-institutionalized adults where attempts were made to establish an etiologic diagnosis. It is not unusual that the individuals in this study had not been seen by a geneticist, or had been seen as a child and not diagnosed. Clinical genetics as a specialty with few exceptions did not emerge until the 1960s. With the recent explosion of genetic information, there are many individuals in the adult population, including those who had a genetic evaluation, that were not diagnosed simply because the disorder had not been described until recently. Currently, due to the increased awareness and knowledge of genetic Number receiving benefit 52 35 28 26 17 16 2 14 7 6 syndromes, most individuals are diagnosed as young children and are typically followed by pediatricians. In adults, however, these syndromes may not be recognized because few training programs for physicians caring for adult patients have formal instruction in genetics in general and dysmorphology in particular. In adults, however, these syndromes may not be recognized because few training programs for physicians caring for adult patients have formal instruction in genetics in general and dysmorphology in particular. In addition, many adults see more than one physician for treatment of their medical problems. This has been implicated as a cause for deficiencies in care of adults [Sifri and Wender, 1999; Kvamme et al., 2001]. In the case of an adult with one of the types of problems identified in this article, attention is frequently focused on the individual problems, and an underlying diagnosis is not pursued. This may also reflect a lack of appreciation of the value of a diagnosis in directing future medical care [Van Buggenhout et al., 1999; Cassidy and Allanson, 2005]. ARTICLE Interestingly, a large proportion of the patients were not receiving recommended adult anticipatory care. This may be a relatively common occurrence [Ruddick, 2005] although in fairness this may not be unique to this population [Institute of Medicine, 2001]. This study may have some utility in informing the medical genetics curriculum proposed by Riegert-Johnson et al. . Based on the frequency of This study may have some utility in informing the medical genetics curriculum proposed by Riegert-Johnson et al. patients seen in this study, exposure to patients (or development of modelpatients) with common connective tissue disorders (Marfan syndrome, Ehlers–Danlos syndrome), chromosomal abnormalities (Down syndrome, 22q11.2 deletion and sex chromosome abnormalities) and mental retardation (fragile X syndrome) could be supported as these types of patients seem most likely to present to an adult primary care provider’s office. While not designed to quantify the value of the genetic consultation in adult patients, this study was able to identify potential benefits for the patients. Many of these individuals and their families received information about etiology, prognosis, and management of their disorders. A significant number of individuals underwent diagnostic testing. This testing was necessary to establish a diagnosis in several individuals. However, in many cases the genetic testing was neither directly diagnostic nor aided in having a previous diagnosis ruled out. Clinical examination by an experienced geneticist obviated the need for testing in many cases. This suggests that the recommendation for a comprehensive clinical examination in the evaluation of children with developmental delay or mental retardation [Moeschler and Shevell, 2006] is applicable to adults as well. This is supported by the work of Taylor et al. . ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c With any intervention, such as genetic testing, consideration of the possible harm to the patient and family must be considered. A literature search on the psychological effects of genetic testing in the context of a diagnostic evaluation such as described in this article did not identify any informative studies in adult patients. Information regarding the impact of genetic testing in late-onset disorders such as Huntington disease and hereditary cancers was readily available. Although this does not directly apply to our study population (late-onset disorders and cancer were eliminated), there may be some relevance. Lawson et al.  showed no statistically significant difference in frequency of ‘‘adverse events’’ (defined in the article as ‘‘a suicide attempt or formulation of a suicide attempt plan, psychiatric hospitalization, depression lasting longer than two months, a marked increase in substance abuse and the breakdown of important relationships’’) between those receiving results indicating increased risk and those suggesting decreased risk. This is applicable in our study population in that predictive testing could become an issue in individuals and families of individuals diagnosed with a genetic syndrome. A negative test result may prove detrimental to an individual and their family in the cases in which a previous diagnosis was excluded. In addition, pressure from family members, unavailability of a genetic test for monetary or insurance reasons, and the possibility of family conflict upon learning the results of a genetic test are also important aspects of genetic testing [Burgess et al., 1998]. Finally, in most cases, a positive genetic test promises nothing in way of a treatment or cure for the disorder, thus inviting the possibility for psychological or social distress [Burgess et al., 1998]. Another aspect of this study population is that a third of individuals in the study had some form of mental retardation. Individuals with MR may not have been able to comprehend as much from their consults as an individual without MR, thus may have benefited less. De Vries et al.  emphasized the difficulty of and necessity for correct assessment of the level of patient understanding. Also emphasized was the need for a certain level of understanding in interpreting test results and making educated decisions about existing options available for care and family planning, as well as the necessity for the geneticist/counselor to refrain from making decisions for their patients with MR. The possible need for family involvement was also discussed. Michie et al.  showed that patients expected ‘‘information, explanation, reassurance, advice and help in making decisions’’ from their genetic consults. These expectations closely match our identified potential benefits. However, as discussed above, the potential benefits in our study were not formally assessed. Thus, we have no measure to determine the patient’s satisfaction with the genetics consult or the patient’s actual benefit. There are several aspects of the study that may limit the applicability of the results to other settings. One relates to the overrepresentation of referrals from psychiatry. One-third of the total referrals came from a single psychiatrist with an interest in psychiatric disorders in the mentally retarded population, who was also familiar with available genetics services. It is important to note that psychiatric illness is a significant concern in this population [Gostason, 1985]. Significant differences were also noted between the two study populations. The WISAR group consisted of adult patients that were referred to an existing pediatric genetics clinic. As the only genetic practitioner in a large geographic area an author (MSW) saw all patients referred for genetic evaluation. With the exception of the patients referred by the psychiatrist, the bulk of the referrals came from physicians who had previously referred pediatric patients. Therefore, the presenting problems were quite similar to those seen in a pediatric clinic with an emphasis on patients with mental retardation or congenital anomalies. As more adult patients were seen, the need for a broad multidisciplinary approach became evident. This lead to the estab- 239 lishment of an adult neurodevelopment clinic staffed by two of the authors (MSW, KDJ), the psychiatrist referenced above, a neuropsychologist, physiatrist, neurologist, and adult disability coordinator. The clinic did a 2-day assessment focusing on diagnosis and coordination of care. Primary care for the patients remained the responsibility of the referring physician, but communication regarding recommendations and treatment plans was enhanced. Additionally, patients who did not have a primary care physician were referred to practitioners identified as having willingness and special interest in management of these special individuals, as well as a history of working cooperatively with the adult neurodevelopment clinic. Most patients referred to this clinic resided in group homes and had significant physical and/ or cognitive disabilities. None of these patients is included in this survey. In contrast, the IM clinic was established as a clinic for adults. Staffed by an author (MSW) and one genetic counselor (JLW), the focus is similar to that of the adult neurodevelopment clinic, without the established group home referral pattern. Referrals from this population have been without any consistent pattern and represent a much broader cross-section of genetic disorders. Clearly, the approach used to establish an adult service, as well as development of the referral network will influence the type of patients that will be seen. The main weakness of this study was the lack of formal assessment of benefit and satisfaction. The informal feedback received in follow-up with the patients and families in this study has been very positive. However, this is clearly an area that needs a more structured research protocol to quantify the benefits to the patients and families. Only through study can the actual needs of this population be known and addressed. In conclusion, this study demonstrates the strong need for traditional genetic services in the adult population and will hopefully provide information that will assist in educating geneticists and others about the special needs in this population. 240 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c REFERENCES Arnulf JM, Zeitzer JM, File J, Farber N, Mignot E. 2005. Kleine-Levin syndrome: A systematic review of 186 cases in the literature. Brain 128:2763–2776. Baird PA, Anderson TW, Newcombe HB, Lowry RB. 1988. Genetic disorders in children and young adults: A population study. Am J Hum Genet 42:677–693. Burgess MM, Laberge CM, Knoppers BM. 1998. Bioethics for clinicians: 14. Ethics and genetics in medicine. CMAJ 159:1085– 1087. Butler MG, Singh DN. 1993. Clinical and cytogenetic survey of institutionalised mentally retarded patients with emphasis on the fragile-X syndrome. J Intellect Disabil Res 37:131–142. Cassidy SB, Allanson JE. 2005. Management of Genetic Syndromes. 2nd edition. Hoboken, NJ: John Wiley & Sons, Inc. De Vries BA, van den Boer-van VDB, den Berg HMA, Niermeijer MF, Tibben A. 1999. Dilemmas in counseling families with the fragile X syndrome. J Med Genet 36:167– 170. Gostason R. 1985. Psychiatric illness among the mentally retarded. A Swedish population study. Acta Psychiatr Scand Suppl 318:1– 117. Hand JE. 1993. Summary of national survey of older people with mental retardation in New Zealand. Ment Retard 31:424– 428. Hand JE, Reid PM. 1996. Older adults with lifelong intellectual handicap in New Zealand: Prevalence, disabilities and impli- cations for regional health authorities. NZ Med J 109:118–121. Haspeslagh M, Fryns JP, Holvoet M, Collen G, Dierck G, Baeke J, van den Berghe H. 1991. A clinical, cytogenetic and familial study of 307 mentally retarded, institutionalized, adult male patients with special interest for fra(X) negative X-linked mental retardation. Clin Genet 39:434–441. Institute of Medicine. 2001. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC: The National Academies Press. Janicki MP, Davidson PW, Henderson CM, McCallion P, Taets JD, Force LT, Sulkes SB, Frangenberg E, Ladrigan PM. 2002. Health characteristics and health services utilization in older adults with intellectual disability living in community residences. J Intellect Disabil Res 46:287–298. Kvamme OF, Olesen F, Samuelson M. 2001. Improving the interface between primary and secondary care: A statement from the European Working Party on Quality in Family Practice (EQuiP). Qual Health Care 10:33–39. Lawson K, Wiggins S, Green T, Adam S, Bloch M, Hayden MR. 1996. Adverse psychological events occurring in the first year after predictive testing for Huntington’s disease. The Canadian Collaborative Study Predictive Testing. J Med Genet 33:856–862. Michie S, Marteau TM, Bobrow M. 1997. Genetic counseling: The psychological impact of meeting patients’ expectations. J Med Genet 34:237–241. Moeschler JB, Shevell M. Committee on Genetics. 2006. Clinical genetic evaluation of the ARTICLE child with mental retardation or developmental delays. Pediatrics 117:2304–2316. Riegert-Johnson DL, Korf BR, Alford RL, Broder MI, Keats BJB, Ormond KE, Pyeritz RE, Watson MS. 2004. Outline of a medical genetics curriculum for internal medicine residency training programs. Genet Med 6:543–547. Ruddick L. 2005. Health of people with intellectual disabilities: A review of factors influencing access to health care. Br J Health Psychol 10:559–570. Sifri R, Wender R. 1999. Defining responsibility for screening. Surg Oncol Clin N Am 8:611–621, v–vi. Taylor MR, Edwards JG, Ku L. 2006. Lost in translation: Challenges in the expanding field of adult genetics. Am J Med Genet Part C Semin Med Genet 142C:294–303. Van Buggenhout GJ, Trommelen JC, Schoenmaker A, De Bal C, Verbeek JJ, Smeets DF, Ropers HH, Devriendt K, Hamel BC, Fryns JP. 1999. Down syndrome in a population of elderly mentally retarded patients: Genetic-diagnostic survey and implications for medical care. Am J Med Genet 85:376–384. Van Buggenhout GJ, Trijbels JM, Wevers R, Trommelen JC, Hamel BC, Brunner HG, Fryns JP. 2001a. Metabolic studies in older mentally retarded patients: Significance of metabolic testing and correlation with the clinical phenotype. Genet Couns 12:1–21. Van Buggenhout GJ, Trommelen JC, Brunner HG, Hamel BC, Fryns J. 2001b. The clinical phenotype in institutionalized adult males with X-linked mental retardation (XLMR). Ann Genet 44:47–55.