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Analysis of 88 adult patients referred for genetics evaluation.

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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: marc.williams@intermountainmail.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
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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
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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
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(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
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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
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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
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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
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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. [2004]. 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. [2006].
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. [1996] 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. [1999] 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. [1997] 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
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