Down syndrome is the most common identified cause of mental retardation. We have described clinical and psychomotor follow-up from 1990–2004 in 322 Sicilian children with Down syndrome. Medical management of the
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Vol. 16 No. 2 2005
Abstract
Down syndrome is the most common iden-
tified cause of mental retardation. We have
described clinical and psychomotor follow-up
from 1990–2004 in 322 Sicilian children with
Down syndrome. Medical management of the
syndrome requires careful assessment, mo-
nitoring, prevention\v and vigilance.
Key-word: Down syndrome, follo\vw-up
Introduction
Down syndrome (DS) remains the most fre-
quent single cause of\v mental retardation.
The prevalence at birth has recently decrea-
sed from one in 700 to\v about one in 1000
1).
As a result of the changes in the practice of
medical care, the lif\ve expectancy in DS has
improved radically in the past few decades
2).
The median age of death has increased and
the average life expectancy in persons with
DS has recently been prolonged to 49 years
of age
3).
Medical management of the syndrome re-
quires an organised approach of assessment,
monitoring, preventi\von and vigilance.
At the Paediatric and Intensive Therapy De-
partment for the newborn of the University
of Palermo 322 subjects (166 males and 156
females) from Sicily are under a follow-up
programme from birt\vh to 18 years of age.
The follow-up consists of a periodic apprai-
sal of the health of the DS child (auxological
and psychomotor follow-up) and a clinical-di-
agnostic programme for recognising the di-
seases most frequentl\vy associated with DS
(congenital malformations, autoimmune dis-
eases, etc.)
It is therefore necessary to know the natural
history of DS, the medical complications oc-
curring and their prevalence at different ages.
Epidemiology
Both neonatal and infant mortality were sig-
nificantly higher in the DS children than in the
general population. The mortality has fallen in the past few years. Between 1978 and
1984 in Italy
4)mortality occurred in the first
month of life in 7.9%of the cases; out of 322
children with DS followed-up from 1990 to
2004, 14 (4.9%) died at various ages: 8/322
(2.5%) of congenital heart disease, 2/322
(0.6%) of leukaemia (one acute lymphatic leu-
kaemia and one acute myeloid leukaemia),
3/322 (0.9%) of severe systemic infections
and one (0.3%) of fetal \vhydrope.
Assessment and manageme\/nt
(from birth to 18 years) ( tab.1)
Clinical diagnosis
and cytogenetic analysis
Although the phenotype is variable, a clinical
diagnosis is possible at birth in most cases
in relation to the characteristic physical fea-
tures. Difficulties can arise in very small ba-
bies, as in the case with premature or small-
for-age newborns, or if there are severe cli-
nical problems that turn the attention away
from the phenotypic characteristics of the in-
fant.
In our experience most cases 319/322 (99%)
have been diagnosed in the first month of life
The chromosome analysis in 309/322 (96%)
showed a standard trisomy 21 originating
from a non-meiotic chromosome disjunction,
in 9/322 (2.8%) a trisomy from unbalanced
robertsonian translocation [of which the
most frequent is the 14/21and in 3/322,
(0.9%) t21;21], «de novo» in 78% of cases,
and in 4/322 (1.2%) there was a mosai\vc tri-
somy with the presence of two cellular lines
(cells with normal karyotype and cells with
trisomy 21). In cases of translocations, the
risk of having another newborn with Down
syndrome is related to the occurrence in one
of the parents of a \vbalanced translocatio\vn.
Communication of the\/ diagnosis
The communication of the diagnosis is, per-
haps, the most delicate moment of the whole
follow-up period of the child with Down syn-
drome and it must be done in two stages: when the diagnosis is suspected and when
it is confirmed.
Clinical and instrumen\/tal
investigations for con\/genital
malformations
Congenital heart disease is the most com-
mon and severe malformation: about 50% of
newborns are affected
5).
In our experience congenital heart disease
was found in 135/322 (42%) cases: in 55/
135 (41%) atrioventicular septal defect, in
43/135 (32%) ventricular septal defect; in
16/135 (12%) secundum atrial septal defect,
in 11/135 (8%) persistent patent ductus ar-
teriosus, in 8/135 (6%) tetralogy of Fallot and
in 2/322 (0.6%) other l\vesions.
All newborn babies with Down syndrome
must be submitted to an echocardiogram by
a paediatric cardiologist, even in the absen-
ce of symptoms
6).
Congenital oral-gastrointestinal tract mal-
formations were frequent (7.3%)
7). In 322 Si-
cilian children with DS congenital gastroin-
testinal tract malformations were identified
in 17 patients (5.2%). The most frequent ano-
malies were: duondenal stenosis in 4/322
patients (1.2%); congenital megacolon in
4/322 (1.2%); anal atresia in 3/322 (0.9%),
oesophageal atresia in 3/322 (0.9%), cleft
palate in 2/322 (0.6%) and diaphragmatic
hernia in 1/322 (0.3%).
Cryptorchidism was found in 28/166 (17%)
males subjects.
Auditory screening
Since sensory defects are frequent in Down
syndrome 8), all the newborns w\vith Down syn-
drome must be submitted to investigations of
the auditory ability (otoacustic emission at
birth and/or brainstem auditory evoked res-
ponse at 3 months). In 4/322 (1.2%) congenital
sensorineuronal deafness was discovered. A
characteristic serous otitis can develop in the
first years of life and can often persist throug-
hout adulthood. A preventive approach to the
hearing problems of \vchildren with DS seems
therefore of the utmost importance in order
to help them to acquire a good communica-
tion ability and sat\visfactory socialisation.
Ophthalmological disor\/ders
Red reflexes should be \vchecked at birth, as
their absence is an important clinical sign of
congenital cataract (15%)
5). In the Sicilian chil-
Clinical and psychomotor follow-up
from 1990 to 2004 in 322 sicil\sian
children with Down syndrome
M. Piccione, C. Lo Giud\vice, M. Martines, L. Graziano, G. Corsello\v
33
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dren with DS congenital cataract was found
in 4/322 (1.2%) patients and a 15-year-old
girl had acquired cataract. Nystagmus was
identified in 64/322 subjects (20%), stra-
bismus in 132/322 (41%) and refractive er-
rors in 167/322 (52%) patients studied.
Investigations for
Hematological abnormalities
During the neonatal period polycytemia
(18%) 5)(that should be treated in order to
avoid cerebral damage), transient myelo-
proliferative disorder
9), 10) , thrombocytope-
nia, thrombocytosis, macrocytosis, lower or
higher leukocyte count and congenital leu-
kaemia(<1%)
5)are frequent. In our experien-
ce polycytemia was found in 70/322 (22%)
newborns while only 3/322 (0.9%) suffered
from transient myeloproliferative disorder and
there was one case of congenital leukaemia.An increased risk of leukaemia in patients
with Ds has been systematically described
and is now well documented
11).
Hemogram, blood glucose examination and
serum IgA, IgM, IgG levels should be check-
ed annually. Liver and renal functionality and
measurement of plasma lipid levels should
be carried out when supported by anamne-
sis or clinical examination.
Out of the 322 children included in the stu-
dy we found 7 cases of leukaemia (1.86%): 4
acute lymphatic leukaemia and 3 acute mye-
loid leukaemia. The median age of diagnosis
was 3.2 years. Leukaemia in patients with DS
occur mostly during the first years of life
12 ).
Screening test for congenital
endocrinological anomalies
Congenital hypothyroidism is much more fre-
quent than in the general population (1%) 13 ).Screening for thyroid disease must be car-
ried out at birth. In our experience congeni-
tal hypothyroidism was reported in 4/322
(1.2%) subjects with DS (3 male newborns
and 1 female newborn).
There is an increased risk of acquired hypo-
thyroidism (about 28%)
13 ). Out of 311 children
over 6 months of age we found subclinical
hypothyroidism in 38/311 (12%) and auto-
immune hypothyroidism in 40/311 (12.8%).
The sex ratio was 2M:1F in both forms of ac-
quired hypothyroidism. The median age at di-
agnosis was 6.2 years for subclinical hypo-
thyroidism and 11.8 for autoimmune hypo-
thyroidism. Appropriate substitutive therapy
is recommended in congenital and acquired
hypothyroidism. The cases with TSH levels
between 11 and 20 mUl may benefit from
treatment with low-dose thyroxine
13 ).
Diabetes mellitus develops in at least 1% of
children and adolescent with DS
14 ). We
Tab. 1: Clinical and psychomotor follow-up in Down syndrome.
– *Adolescents and young adult Down subjects with no known cardiac disease can develop mitral valve prolapse and aortic regurgitation.
– ** Hemogram, blood glucose examination, and immunologic deficiencies should be checked annually.
– *** At 3 to 5 years X-rays for atlantoaxial instability/ subluxation are necessary.
– The vaccinations according to local programs and specific vaccinations for age or if at risk (influenza, pneumococcal etc) should be carried out.
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Vol. 16 No. 2 2005
found only one case, but other two of the fa-
mily were affected.
Screening for celiac disease
Celiac disease has an increased prevalence
in DS, ranging from 4 to 17% 15 ). After the first
year of life the subjects are screened for ce-
liac disease.
303 children over a year old included in the
study, were screened for celiac disease using
IgA and IgG antigliadin testing, IgA EMA; IgA
and IgG anti-transglutaminase antibodies.
18/303 (5.9%) were positive on screening
and an intestinal peroral biopsy confirmed
the diagnosis. In all the subjects the celiac
disease was silent. The median age at dia-
gnosis was 4.8 years. The basic treatment of
celiac disease is a gluten-free diet that leads
to a complete recovery. A strong commit-
ment and constant surveillance are required
for patients, because compliance is often dif-
ficult to obtain. The sex ratio was 1M:1F. In
11 patients celiac disease and autoimmune
hypothyroidism were both present.
Orthopaedic controls
Muscular and othopaedic anomalies are well
know in DS. Muscular hypotonia and joint
hyperlaxity are almost constant. Flat foot,
genu valgum and patella instability are the
main causes of walking problems and even
of severe static troubles such as scoliosis
and cyphosis. In our experience 4/322 (1.2%)
suffered from severe scoliosis which obliged
them to wear a correction corset. All patients
had flat feet. About 13% of subjects with DS
have subluxation of the cervical spine but are
asymptomatic. An additional 2% of individu-
als with DS develop signs and symptoms of
spinal compression
1). At 3 to 5 years X-rays
should be carried out to discover eventual at-
lantoaxial instability or subluxation. The re-
commended method has been a lateral neck
x-ray in neutral, flexed and extended posi-
tions. Diagnosis is confirmed by X-rays that
demonstrate a distance of 4.5–5 mm bet-
ween the anterior side of odontoid process
and posterior margin of the anterior atlas
arch
1). In 27/195 (13.8%) subjects asympto-
matc atlantoaxial subluxation was found. Ma-
nagement of subjects with syntomatic sub-
luxation requires immediate stabilization and
surgery must be taken into consideration.
One case of congenital hip dislocation and
one of acquired hip dislocation were found.
In 2 patients patella instability was identified.
Dental controls
Dental anomalies are a common problem
whose solution is not an easy task. Moreover,
objective difficulties are found in examining
and specifically treating children and adults
with DS. A peculiar dental anatomy, deve-
lopmental anomalies and malocclusion are
frequent. In our experience gingivitis and pe-
riodontal disease are frequent (50% of cases).
Neurological observation
The frequency of seizure disorders in patients
with DS is greater than in the general popu-
lation
1), 16 ) . Out of the 322 children included in
the study 10 (3%) had had seizure disorders.
Neuromotor and cognitive
developmental
Early intervention programs are designed to
comprehensively monitor and enrich deve-
lopment, focusing on feeding, gross and fine
motor development, language and personal
and social development. Patients with DS fre-quently understand the spoken language bet-
ter than they can express themselves ver-
bally. In our cases the psychomotor delay
was of a medium degree with most problems
in the language and cognitive fields.
Prevention of obesity
Individuals with DS have reduced resting
metabolic rates, which contribute to a higher
frequency of obesity than in other subjects
17 ).
In our experience 9/322 (2.7%) patients with
DS became obese as time went on. The use
of growth charts for Sicilian children with
DS
18 )is especially helpful in assessing whet-
her an early weight-for-height growth pattern
is abnormal. Practical advice, therefore, and
good «nutritional education» should be im-
parted to the family and by the family, as-
sociated with sports activities.
Discussion
Children with DS have benefited from the ad-
vances in medical care with a reduction in in-
fant mortality.
Tab. 2: Congenital malformations and acquired disease in 322 Sicilian children with DS * Congenital leukaemia, atlantoaxial subluxation and transient myeloproliferative disorder are not found
in normal population.
% in down % in normal
Disease Frequenzy syndrome population
Congenital heart disease 135/322 42 0.4
Congenital oral-gastrointestinal 17/322 5.2 0.06
tract malformations
Cryptorchidism 28/166 17 3–5
Congenital sensorineuronal deafness 4/322 1.2 0.1
Congenital cataract 4/322 1.2 0.4
Nystagmus 64/322 20 0.007
Strabismus 132/322 41 3–5
Polycytemia 70/322 22 5
Transient myeloproliferative disorder 3/322 0.9 *
Congenital leukaemia 1/322 0.3 *
Leukaemia 7/322 1.86 0.0033
Congenital hypothyroidism 4/322 1.2 0.025
Acquired hypothyroidism 78/311 24 0.11
Celiac disease 18/303 5.9 0.5
Atlantoaxial subluxation 27/195 13.8 *
Seizure disorders 10/322 3 0.66
Periodontal disease 161/322 50 1–10
35
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The availability of accurate information on
survival of DS is an important requirement
for clinical management, health care servi-
ce provision and genetic counselling.
Tertiary prevention includes the evidence of
complications in affected patients (Tab. 2). In
the specific case of DS patients, those pre-
ventive actions include early psychomotor
stimulation, adequate paediatric handlings of
acquired pathologies (acquired hypothyroi-
dism, celiac disease, diabetes mellitus, at-
lantoaxial instability or subluxation, seizure
disorders, etc.) and congenital pathologies
(congenital hypothyroidism, congenital sen-
sory-neuronal deafness etc.), the timely sur-
gical correction of associated defects (con-
genital heart disease, congenital gastroin-
testinal tract malformations, congenital
cataract etc.) and the effective acceptance
by the community into its educational system
and labour force.
Correspondence:
Prof. Giovanni Corsello
Direttore Clinica Pediatrica
U.O. Pediatria e Terapia Intensiva
Neonatale Dipartimento Materno-Infantile
Università di Palermo
giocors@aliceposta.it
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Informations complémentaires
Auteurs
Prof. Giovanni Corsello , Direttore Clinica Pediatrica U.O. Pediatria e Terapia Intensiva Neonatale Dipartimento Materno-Infantile Università di Palermo