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CHARGE association Clinical manifestations and developmental outcome.

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American Journal of Medical Genetics 39:48-55 (1991)
~
~
CHARGE Association: Clinical Manifestations
and Developmental Outcome
A. Simon Harvey, Patricia M. Leaper, and Agnes Bankier
Murdoch Institute (A.S.H., A.B.) and Department of Psychology (P.M.L.), Royal Children?s Hospital, Melbourne,
Australia
Mental retardation and growth failure are
considered integral manifestations in the
CHARGE association, reported to be present
in as many as 90% of cases. Recent studies
have reported a better than expected outcome
in some patients; however, the conclusions of
these studies have been confounded to some
extent by their inclusion criteria. We report
follow-up of 17 patients with CHARGE association in whom the diagnosis was based on
clinical findings present in early infancy, before developmental patterns were established. Of the 7 survivors, all had motor delay,
and 6 had feeding difficulties during infancy.
Psychometric assessment at follow-up (age
range 2 years, 10 months, to 15 years) showed
that 2 were functioning in the normal range, 3
had specific language delay, one had moderate mental retardation, and one had severe
mental retardation. Feeding problems persisted in only the 2 youngest patients. After
initial failure to thrive, normal height was
reached in 4 of 5 children older than age 3
years. The effects of visual and hearing deficits, their management, and the effects of
physical illness are discussed with respect to
developmental outcome. Our results suggest
that some infants with CHARGE association
who survive early infancy have a better prognosis for feeding difficulties, growth, and
mental development than may be expected
from early performance and better than that
generally predicted from the current literature. The prompt management of sensory deficits is emphasized.
KEY WORDS: mental retardation, coloboma,
choanal atresia
Received for publication March 19,1990; revision received Ju n e
20, 1990.
Address reprint requests to Dr. Agnes Bankier, Murdoch Institute, Royal Children?s Hospital, Flemington Road, Parkville,
Melbourne, 3052 Australia.
0 1991 Wiley-Liss, Inc.
INTRODUCTION
The nonrandom association of coloboma, choanal
atresia, and other congenital abnormalities has long
been recognized [Angelman, 1961; Edwards et al., 1961;
Stool and Kemper, 1968;Buckfield et al., 1971;James et
al., 1974; Ho et al., 1975; Sassani and Yanoff, 1977;
Hittner et al., 1979;Hall, 1979;Lillquist et al., 19801. In
1981, Pagon et a1 proposed the acronym CHARGE to
designate this association (coloboma, congenital heart
disease, choanal atresia, retarded growth and development andlor structural brain abnormalities, genital hypoplasia, and ear anomalies andlor deafness). Subsequent reports have supported this association and have
added esophageal atresia, facial palsy, renal abnormalities, and cleft lip and palate to the clinical spectrum
[Warburg, 1983; Koletzko and Majewski, 1984; Kaplan,
1985; Davenport et al., 1986al. Recent reports have examined in detail the cardiac defects [Lin et al., 1987;
Cryan et al., 19871, external ear anomalies [Davenport
et al., 1986133,auditory and temporal bone abnormalities
[Thelin et al., 1986; Wright et al., 1986; Guyot et al.,
19871, choanal obstruction [Bergstrom and Owens,
1984; Leclerc and Fearon, 1987; Brown et al., 1987;
Duncan et al., 19881, and endocrine defects [Augsut et
al., 1983; Pardo and Chua, 19851in the CHARGE association.
Most cases are sporadic, with no recognizable cause;
however, there are reports of familial CHARGE syndrome [Ho et al., 1975; Pagon et al., 1981; Awrich et al.,
1982; Mitchell et al., 198510;Metlay et al., 19871,including concurrence in monozygotic twins [Levin et al.,
1973; Oley et al., 19881. The underlying pathogenesis is
postulated to be developmental arrest occurring about
the sixth week of embryogenesis, involving primarily
neural crest elements [Siebert et al., 19851.
Mental retardation and retarded growth are considered an integral part of the condition, present in about
90% of cases [Jones, 19881. This has been of concern to
neonatologists, surgeons, and parents of infants with
these major congenital abnormalities and in some cases
may have affected management. A recent report has
suggested a more favorable outcome in some children
[Oley et al., 19881, and this was the experience at our
institution. The following study was initiated to determine the developmental outcome of patients with
CHARGE Association
49
CHARGE association in whom the diagnosis could be
made in early infancy.
years. Chromosome analysis was normal in all 14 patients examined.
MATERIALS AND METHODS
To identify all patients with CHARGE association
seen a t the Royal Children?s Hospital, Melbourne, during the period 1976-1986, hospital records were
searched for the inpatient diagnoses of CHARGE association or coloboma or choanal atresia. Patients were
included in this study only if the diagnosis could be
made on clinical findingspresent in early infancy. Criteria for diagnosis were the presence of coloboma andlor
choanal atresia with a total of a t least 4 of the 7 major
abnormalities: coloboma, heart defect, choanal atresia,
growth failure, mental retardationhain abnormality,
genital hypoplasia, ear abnormalityldeafness [Pagon et
al., 19811. All patients had a sufficient number of findings of the CHARGE association for case selection without needing to include mental retardation. Failure to
thrive was coded when length and weight measurements crossed centile lines, and in all patients this was
to below the 3rd centile for age. All patients included in
the study satisfied the ?definite? diagnostic category
when applying the suggested Expert Model for
CHARGE association [Mitchell et al., 1985al.
A total 17 patients were ascertained. Ten patients had
died, and 7 of these underwent a n autopsy. All 7 live
patients were interviewed and personally examined by
A S H . , and 6 underwent formal psychological assessment by P.M.L.
Physical Findings
The clinical findings present in early infancy are
shown in Table 11. Colobomata (15 of 17 patients) were
bilateral in 11 patients and associated with microphthalmia in 6 patients. Congenital heart defects were
present in all patients who died and in 4 survivors. Five
5
kg
45
9000
4
BIRTH
WEIGHT
35
50�
3
1000
2 5
2
15
1
5
24
26
28
30
32
34
36
38
40
42
55
cm
90 %
50%
50
RESULTS
1 OD.
Eight males and 9 females were ascertained. Of the 10
patients who died, 7 died neonatally, and 2 patients
(numbers 11 and 13) lived to 6 months. Of the 7 survivors, the age range a t follow-up was 2 years, 10
months, to 15 years, 1 month.
45
Perinatal Manifestations
The birth details of the 17 patients are summarised in
Table I and the growth parameters are graphed in
Figure 1. Six patients were born prematurely, and 3
were small for gestational age. Apart from polyhydramnios in mothers of fetuses with esophageal atresia, pregnancy histories were unremarkable. Family histories
were unremarkable. The average maternal age was 29
30
40
9000
50�
5
35
-E
N
G
L/
10ao
25
HEAD
CIRCUMFERENCE
24
26
28
30
32
34
36
38
40
42
Weeks of Gestation
Fig. 1. Graph ofbirth weight, length, and head circumferencefor all
patients for whom results were available.
TABLE I. CHARGE Association: Perinatal Manifestations*
Sex
Delivery
Gestation (weeks)
A score
1 min
5 min
Birth weight (kg)
Length (cm)
Head circumference (cm)
1
M
N
40
2
M
Fo
34
5
5
5
7
2.40 2.53
47.3
32.5 34.0
Alive
4
5
F
M
M
N
C
Fo
40 31 40
3
5
Deceased
12
13
14
~~~
6
7
8
9
F
N
40
M
N
38
M
N
40
F M M
C
C
38 37 38
10 11
F
C
34
15
16
F
N N F o
35
36
37
F
F
35
38
F
F
-~
17
4
4
1
0
7
4
3
2
5
3
2
4
4
7
6
6
8
10
10
7
5
6
6 5
7
6
6
7
9
6
3.47 1.26 3.25 2.97 3.02 3.09 2.01
3.00 2.03 2.34 2.68 2.08 2.64 2.68
49.5
50.5 47.0
44.5
34.5
34.5
29.9
31.3 32.0 33.5 35.0 33.0 32.0
*Abbreviations: N, normal; Fo, forceps; C, cesarean section.
50
Harvey et al.
TABLE 11. CHARGE Association: Clinical Findings in Early Infancy*
Alive
~-
1
2
3
4
5
6
7__
.
8
9
10"
11
Deceased
12"
13"
14"
~~
Coloboma
R
B
B
B
B
L
B
B
R
B
L
B
Heart
+ - + + - + + + + + + +
Choanal atresia
+ + + + - + + + + + + +
Retarded growth
+ + + + + + + I
I
i
+
I
+
Feeding problems
+ + + + + + +
+
+
l
+
Brain anomaly
+ + +
+
+
Hypogenitalism
+
I
I
+
+
I
+
+
I
I
Ear anomaly
+ + + + + + + + + +
+
+
+
Deafness
+
+
+
+
+
+
I
I
I
(
+
)
l
(
+
)
Middle ear disease
+ + + + + + + I
I
I
+
I
+
Facial palsy
R
R
+ L- L- L+ L- R- R- - - Esophageal atresia
Cleft lipipalate
P
P
P
L
P
P
L
Renal anomaly
+
+
+
Micrognathia
+ + + - + + + +
+
Abnormal face
+ + + + - + +
+
+
+
Skeletal anomaly
+ - - + - - + - + + *Abbreviations:+ , present; - , absent; i , not applicable; R, right; L, left; B, bilateral; P, palate; L, lip.
B
+
+
15"
16"
_ _ _ _ _
B
+
+
l
+
+
l
I
l
I
I
L
+
+
-
+
~~
+
-
I
I
17"
_ _ ~ ~ ~ ~
+
+
l
+
I
+
B
+
I
+
++
+
-
+
I
+
+
I
+
I
i
I
++
+
+
+
-+
+
+
+
I
"Autopsy.
were born with cyanotic heart disease, including patients l and 5 with tetralogy of Fallot. Choanal atresial
stenosis (14 of 17 patients) was bilateral in all but one
patient. Hypogenitalism was diagnosed in boys with
small genitalia for age andlor bilateral cryptorchidism
(5 of 8 patients). Patient 2 had proven gonadotrophin
deficiency and was treated with testosterone injections.
Patient 6 was prepubertal a t age 15years. The ears were
abnormal to some degree in all patients, the most common abnormality being small, square or triangular, and
apparently low-set ears with simple helices and small or
absent lobes. All 9 patients who lived to a t least age 6
months had chronic middle ear infectionlfluid, 7 of 9
required middle ear drain tubes and 6 of 9 had confirmed
moderate-severe bilateral mixed hearing loss (the 2 deceased patients were suspected of being deaf). Only patient l had normal audiometric findings. Some typical
findings are shown in Figure 2 (patient 3).
Unilateral facial palsy was present on the side of the
more abnormal ear in 8 of 9 patients. Only 2 of the
deceased patients were documented to have facial asymmetry; however, this may not have been noted in sick
newborn infants or a t autopsy. A number of mild skeletal abnormalities, mostly digital, were seen in our pa-
Fig. 2. Patient 3 at age 6 weeks showing a:right iris coloboma, nasal tubes for choanal atresia, and left
facial palsy; b: micrognathia; and c: square-shaped left ear with prominent antihelix, triangular concha,
and absent lobe.
CHARGE Association
tients. Ofparticular note was patient 2, who had 11ribs,
fusion of the sixth and seventh cervical vertebrae, and
abnormal neural arches in the third and fourth thoracic
vertebrae. Minor facial anomalies included prominent
nasal bridge, flattened nose, and down-slanting palpebral fissures. Patient 17 had a horseshoe kidney and 5
other patients had minor abnormalities of renal size and
structure.
Brain Abnormalities
Olfactory tracts were absent in 7 of 7 brains examined.
Cerebellar dysplasia or hypoplasia was present in 4 and
a Dandy Walker cyst in one. Two deceased infants without autopsy had a n abnormality on ultrasonography:
agenesis of the corpus callosum and absent septum pellucidum. Mild ventricular dilatation was present in 2
deceased patients. Results of cranial ultrasonography of
patients 1, 2, and 6 during infancy were normal.
Feeding
Feeding problems during infancy were of major concern in 16 of 17 patients. Prolonged gavage feeding was
required in most instances. Patients 4, 7, and 13 required feeding by gastrostomy tube. Of the patients seen
at follow-up, feeding problems improved in 4 of 6 , although one had persisting mild nasopharyngeal incoordination. Patients 4 and 7 still required gastrostomy
tube feeding.
Growth
Growth curves on 6 of 7 live patients are shown in
Figures 3 and 4 (patient 6 insufficient data). Failure to
thrive was present in 7 of 7 surviving patients a t some
time during infancy but catch-up growth and normal
height velocity were achieved after the first 1-2 years
in 4 of 7 patients. The normal range for height was
reached in 4 of 5 patients older than age 3 years, but only
2 of 5 were in the normal range for weight. Patient 3
achieved the 50th centile for all parameters. In patients
4 and 6, head circumference a t follow-up was below the
second centile, but in proportion to their severe growth
failure. The 3 patients who died after the neonatal period had growth parameters <3rd centile for age.
Development
The results of psychological assessments performed a t
the time of review are summarised in Table 111. The
particular psychometric tests employed were selected
according to the child?s age and relevant disabilities.
Two children were functioning in the normal range for
age, 3 had language delay with performance in the normal range for nonlanguage tasks, one had moderate
mental retardation, and one had severe mental retardation. For 6 of 7 patients it was thought that developmen-
HEIGHT/SUPINE LENGTH (Cm)
97
150
1
2
MASS (kg)
_------
..........
3 ................
140
1
51
4-
97
5
7
2
40
3
130
................
4-
120
5-
7
110
30
100
3
20
90
an
L
10
I
1
2
3
,
I
4
l
5
l
6
I
7
I
I
8
9
1
I
0
Age (years)
Fig. 3. Growth for weight in all patients except patient 6 (insufficient data).
A g e (years)
Fig. 4. Growth for height in all patients except patient 6 (insufficient data).
52
Harvey et al.
TABLE 111. CHARGE Association: Developmental Findings (yearslmonths)at Follow-Up*
Patient
1
2
3
4
5
6
7
Age at
testing
317
712
418
2/11
719
1511
2110
Sat
Walked
First
words
110
110
110
210
110
210
111
+
-
-
214
1/11
118
110
-
-
1/10
410
-
ADL
+
/
+
Psychometric tests
~~~~~
Stanford-Binet
Hiskey-Nebraska
WPPSI
Bayley
Reynell-Zinkin
Gross
motor
N
N
N
019
N
Language
Nonlanguage
N
410
N
N
7 10
N
118
N
110
310
MR
119
-
10
I
Bayley
019
tal outcome was in part dependent on associated physical illness, nutrition, visual or auditory disabilities and
their management, social or family factors, or appropriateness of treatment. The relevant details of each
child?s growth and development are outlined briefly in
Appendix A.
~
+ , present,
Behavior
problems
N
?
?
~
*Abbreviations N, normal for age, MR, mental retardation, ADL, activities of daily living,
Overall
-
- , absent, /,
+
++
+
+
++
-
not applicable
necessarily be obvious clinically or on ultrasound, the
difference may not be a real one. Absent olfactory tracts
were seen in all our infants examined a t autopsy, and
were suggested from suspected anosmia in patients 2
and 3. Arrhinencephaly has been reported less frequently in other series [Stool and Kemper, 1968; Ho et
al., 1975; Pagon et al., 1981; Siebert et al., 1985; Duncan
DISCUSSION
et al., 19881.
The aim of this study was to determine the outcome
Feeding difficulties were almost universal in infancy;
for growth and development in infants with CHARGE however, only the 2 youngest patients (patients 4 and 7)
association. Previous reports have been difficult to inter- had continuing problems a t the time of review. Alpret because of a n ascertainment bias when using men- though nasopharyngeal incoordination and gastrotal retardation as a diagnostic criterion. To avoid this esophageal reflux are common in CHARGE association,
bias, and to provide information useful to the neonatolo- prolonged feeding difficulties were seen in the children
gist and geneticist, we studied only patients in whom the with retarded neurological development.
diagnosis was, or could have been, made on clinical
Six of the 7 live children had birth weights that were
findings in early infancy, before patterns of growth and appropriate for gestational age. Postnatal growth paraldevelopment were established. Infants with known leled oral feeding, with catch-up growth evident after
mental retardation were included only if the diagnostic infancy. As stated, 4 of the 5 older children were >3rd
criteria were met on the basis of other abnormalities centile for height a t follow-up, although all but two were
[Pagon et al., 1981; Mitchell et al., 1985al. A number of ~ 3 r centile
d
for weight. This pattern of growth was also
older children with the diagnosis of CHARGE associa- seen in the original description of Pagon et al. [19811 as
tion were excluded from the study because clinical ab- well as in a recent follow-up study by Oley et al. [19881.
normalities supporting their diagnosis, such as mild Postnatal growth deficiency and pubertal delay may in
retardation, short stature, and deafness were not appar- part to be due to hypopituitarism [Pardo and Chua,
ent in early infancy.
1985; August et al., 19831 and poor nutrition and the
Considering the whole patient group, the spectrum of result of associated medical and surgical problems.
clinical findings is similar to that previously described.
The results of psychological assessments in the chilOf particular note, we found a high prevalence of deaf- dren followed in this study suggest that there is a specness and chronic otitis media and a high frequency of trum of developmental outcome, including normal abilibrain abnormalities.
ties. The study did not aim to determine the incidence of
Moderate to profound deafness occurred in up to 85% mental retardation but does suggest that it may not be
ofreported cases LThelin et al., 19861and in all but one of as high as usually stated. Two of our patients were
our patients. Although evaluation of hearing is techni- functioning in the normal range for age. In patient 1,
cally difficult in these children, it appears that deafness sensory deficits and medical problems were minimal.
arises as a result of congenital defects of the ossicular Although patient 3 had significant visual and hearing
chain; ?dysplasia? of the bony labyrinth, eustachian deficits, these were detected and appropriately managed
tube dysfunction due to craniofacial abnormalities; and from a n early age. For both of these children, we think
a degree of congenital, high-frequency, sensorineural that the relative lack of sensory deprivation was a sigloss [Wright et al., 1986; Leclerc and Fearon, 1987; nificant positive factor in their development. In conGuyot et al., 19871.
trast, patient 5 was incorrectly assessed in his abilities
Neurological problems are common in CHARGE asso- from a n early age and not adequately treated and educiation: absent olfactory tracts (cranial nerve 11, col- cated until very late. He and patient 2 had similar autisoboma (CN2), facial palsy (CN71, deafness (CNS), tic-like behavior and severe delay in language developbulbar problems (CN9, lo), epilepsy, and degrees of de- ment. Patient 7 best exemplified the possible false
velopmental delay. Structural brain abnormalities were impression of primary mental retardation in these chilseen in most of the deceased infants but in none of those dren when a t age nearly 3 years he had gross motor
living. In that some of the brain abnormalities would not delay and no verbal language. However, he was found to
CHARGE Association
be deaf and later shown to perform nonlanguage skills
up to 1year above his chronological age. This pattern of
language delay was seen in 3 patients in our study and
occurred in the context of sensory deprivation. It is difficult to be sure whether this represents a primary language disorder or language delay secondary to sensory
deprivation. Of the 2 patients who were assessed as
being globally delayed in development, patient 6 clearly
had primary mental retardation. In patient 4 there were
significant perinatal, medical, and sensory problems
contributing to his delay. Importantly, gross motor delay was present during infancy in all our children with
CHARGE association and therefore was not predictive
of later developmental achievement.
It is difficult to determine the frequency and degree of
retardation in CHARGE association patients from the
literature due to differences in ascertainment and definition, grouping of data, and lack of formal psychometric
testing. Pagon et al. [1981] reported one normal individual and 3 mildly retarded individuals in their early
report of 19 patients with CHARGE association; the
remainder were more significantly retarded. Davenport
et al. [1986al reported one mildly retarded patient and
one patient with language delay in their 9 patients;
again, the others were more severely retarded.
Goldson et al. [19861 first published details of psychometric studies in two patients with CHARGE association and emphasized the need to treat sensory deficits
aggressively. A recent study by Oley et al. [19881 reported 8 of 20 children with CHARGE association with
normal intelligence (aged 16 months to 14 years). Of the
remainder 9 had an I& of 50-70 (and problems with
hand-eye coordination and speech) and 3 had a n I& of
<50. Unfortunately, the details of assessment methods,
associated disabilities, and other contributing factors
were not available in this report.
In the 7 children followed, physical growth, feeding,
and neurological development paralleled each other.
However, no clinical findings present neonatally or in
early infancy correlated with developmental outcome.
In fact the lowest 5 min A scores of the survivors were
recorded in the 2 patients with the best outcomes. The
subsequent progress of the 2 youngest patients will be
very important to follow.
Our findings, and those in recent reports, suggest
that, in some infants who survive the newborn period,
the prognosis may be better than expected. Early feeding problems are likely to improve, catch-up growth to
the low normal range can occur, and early gross motor
delay does not necessarily indicate a worse prognosis.
Although concurrence of cyanotic congenital heart disease and choanal atresia was associated with a worse
prognosis for survival, no clinical features in infancy
were predictive of developmental outcome. Developmental outcome in many of these children will be influenced
greatly by factors such as the presence of structural
brain abnormalities, the presence and severity of visual
and hearing deficits, early management of these sensory deficits, adequate feeding and nutrition, adverse
perinatal factors, coexistent medical and surgical problems, and implementation of early intervention strategies and family supports. Pediatricians need to be par-
53
ticularly alert to the problems of visual and hearing
deficits, which may be difficult to detect in infancy or
develop during later childhood.
ACKNOWLEDGMENTS
We thank Ms. Kati Bromley for her assistance in
preparing the figures.
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Pagon RA, Graham JM, Zonana J, Yong SL (1981): Coloboma, congenital heart disease, and choanal atresia with multiple anomalies:
CHARGE association. J Pediatr 99923-227.
Pardo JM, ChuaC (1985):The CHARGE Association in a male newborn
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Sassani JW, Yanoff M (1977):Anophthalmos in an infant with multiple congenital anomalies. Am J Ophthalmol 83:43-48.
Siebert JR, Graham JM, MacDonald C (1985):Pathological features of
the CHARGE Association: Support for involvement of the neural
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Pediatrics 42:525-528.
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Association. Part 11. Hearing loss. Int J Pediatr Otorhinolaryngol
12:145-163.
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2:189-199.
Wright CG, Meyerhoff WL, Brown OE, Rutledge J C (1986): Auditory
and temporal bone abnormalities in CHARGE association. Ann
Otol Laryngol 95:480-486.
~~~
APPENDIX
Patient 1 (Male, Normal Abilities)
The diagnosis of CHARGE association was made neonatally. A total of 83 days were spent in hospital during
the first year of life for operative repair of esophageal
atresia and tetralogy of Fallot. Initial feeding problems
and failure to thrive resolved, and general health remained good. Catch-up growth to the 3rd centile for
height and weight and 50th centile for head circumference had occurred at the time of review. Visual acuity
in left eye and hearing were normal. Prior to assessment
he had been attending a special preschool, because early
development had been delayed. When assessed a t age 3
years, 7 months, with the Stanford-Binet test and subtests of the McCarthy scales, he was found to be functioning in the average range. Some difficulties were
noted in the areas of memory, visual-motor coordination, concentration, and behavior.
Patient 2 (Male, Language Delay)
The neonatal period was uncomplicated following
birth a t 34 weeks of gestation. CHARGE association was
diagnosed a t age 5 months. Nasogastric feeding, complicated by reflux and aspiration, was required until age 1
month. Visual acuity was normal. One hundred decibel
mixed hearing loss was present, and aids were fitted a t
age 20 months. Multiple middle ear drain tubes were
needed, and good aided thresholds eventually were
achieved. Although there were no significant medical or
surgical problems present, added factors thought to be
involved in this patient's early developmental delav
were the unavail&lity of appropriate family supports
and inadequate early intervention. Seizures occurred
between ages 1and 4 years. When Seen at age 7 years, 2
months, height and weight were between the 3rd and
lothcentiles and head &cumference was a t the 50th
centile. He had no speech and had many autistic behavioral traits. When tested on the Hiskey-Nebraska test of
learning aptitude, he was in the 4 year range for tasks
involving higher language functions but was up to ageappropriate levels for tasks without language 'Ontent'
Patient 3 (Female, Normal Abilities)
CHARGE association was diagnosed neonatally. Initial feeding problems and failure to thrive began to
resolve after age 3 months, and from age 2 years growth
velocity was normal. When she was reviewed a t age 4
years, 8 months, growth parameters were a t the 50th
centile. Bilateral inferior retinal coloboma, myopia
( - 20D), and astigmatism necessitated spectacles a t 13
months, with corrected binocular visual acuity being
6/36. To correct for a 50-90 dB mixed hearing loss, aids
were fitted a t age 17 months and middle ear ventilation
tubes were inserted on two occasions. Excellent aided
thresholds and speech discrimination resulted. Apart
from the need for repeated nasal surgery,general health
remained good. Psychomotor development was delayed
in infancy but accelerated once sensory deficits were
managed. Intensive early intervention, excellent family
supports, early preschool placement, and the provision
of school integration aides were all important extra factors in her progress. At age 4 years, 8 months, she was a
friendly and cooperative girl, who, when tested using
the WPPSI without accommodating for her visual handicap, was functioning well within the normal range for
age. In particular, she had excellent language abilities
for age and was reported to be doing well at a normal
school on follow-up 8 months later.
Patient 4 (Male, Moderate Mental Retardation)
This infant was born by emergency cesarean section
at 31 weeks of gestation and weighed only 1,260 g. He
required prolonged hospitalization for respiratory distress, esophageal surgery, ligation of patent ductus arteriosus (PDA), choanal surgery, recurrent chest infections, and feeding problems. Gastrostomy tube was
inserted at age 4 months, and, when reviewed a t 2 years,
11 months, he was still not taking food by mouth. All
growth parameters were well below the 3rd centile. A
large disc coloboma was present in the left eye, but only a
small choroidal defect was present in the right. The left
external auditory canal was atretic, and a 70 dB mixed
hearing loss was present on the right. At age 13 months,
hearing aids were prescribed but were not worn due to
auricular hypoplasia and marked tactile defensiveness.
Very little developmental progress occurred during the
first 12 months, and, when assessed using the Bayley
Scales a t age 2 years, 11 months, he was found to be
performing a t approximately a 12 month level overall.
In particular, all language items were failed, gross motor level was about 9 months, but some visual-motor
tasks were passed a t a 20 month level. Tactile defensive-
CHARGE Association
ness and oral hypersensitivity interfered with ongoing
therapy. Early intervention programs had been implemented and there was evidence of recent developmental
acceleration.
Patient 5 (Male, L a n g u a g e Delay)
After 2 months in hospital with feeding problems and
failure to thrive, he began to show catch-up growth.
When seen a t age 10.5 years, all growth parameters
were a t approximately the 3rd centile for age. Tetralogy
of Fallot was not repaired until age 8.5 years. Bilateral
retinal and disc colobomata were present. Initial predictions were of blindness, mental retardation, and probably adequate hearing. He was in a play group for blind
children initially, and then in a day training center for
intellectually disabled children. At age 7 years, spectacles were fitted, and he had good functional vision (acuity of 6/18-6/24). A 90 dB hearing loss was detected,
and well functioning hearing aids were eventually fitted
a t age 8 years, 5 months. The diagnosis of CHARGE
association was not made until he was seen a t age 10.5
years by one of the authors. During the 2 years prior to
our assessment, he had been taught in a small group a t a
deaf-blind school. We were not allowed to test this boy
formally, but a n assessment was performed a t age 7
years, 9 months, by another agency. With the ReynellZinken scales for young visually impaired children and
the Vineland adaptive behaviour scales, he showed
global developmental delay. In particular, language was
a t the 1 year level, perceptual motor skills a t the 4-5
year level, and motor skills at the 3 year level compared
with partially sighted (hearing) children. When seen 2.5
years after this assessment, and following the delayed
management of his sensory deficits, there had been a
marked reduction in autistic-like behavior and improvement in communication, although using a picture card
system predominantly.
Patient 6 (Female, Severe Mental Retardation)
Although this girl had no major cardiorespiratory or
surgical problems a t birth, she required nasogastric
55
feeding until age 18 months. At this age she underwent
cleft palate repair and a traumatic transition to oral
feeds. Vision and hearing were not greatly impaired by
iris coloboma and moderate hearing loss, respectively.
When seen at age 15 years, she was severely intellectually retarded, with no speech and near-total dependence with regard to activities of daily living. In unfamiliar surroundings, she was vigorously uncooperative
such that formal psychometric testing was not possible.
All growth parameters, including head circumference,
were well below the 3rd centile for age. The diagnosis of
CHARGE association was first made a t this time.
Patient 7 (Male, Language Delay)
This patient?s first 2 years were complicated by severe
upper airway obstruction and hypoxia requiring nasopharyngeal tubes, tracheostomy, adenotonsillectomy,
and home overnight oxygen. Feeding problems and recurrent aspiration necessitated a gastrostomy tube and
a total of 4 attempts a t fundoplication. A total of 212
days was spent as a hospital inpatient. Only a left inferior retinal coloboma was present, and repeated audiometric studies initially excluded all but a mild hearing
loss. At age 2 years, 9 months, following repeated middle
ear infections, auditory brainstem responses suggested
significant deafness. Vocalization and a notable change
in behavior followed the fitting of hearing aids. Psychomotor development was delayed, and he was attending
?early intervention?? programs. Tactile defensiveness
and oral hypersensitivity were compounding problems.
When he was seen a t age 2 years, 10 months, head
circumference was normal for age, but height and
weight were below the 3rd centile. He had no speech and
had only recently begun to take food by mouth. On the
Bayley scales (tested 7 month before the fitting of hearing aids),he failed all language items but surpassed the
30 month level for all nonlanguage items. Some nonverbal items on the Merrill-Palmer scale of mental tests
were passed up to the 4 years level. Motor skills were a t
the 9 month level, and, although a n overall estimate of
abilities was 21 months, mental retardation was excluded.
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