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
Fortbi\bdung / Formation continue
32
Vo\b. 16 No. 2 2005
Abstract
Down syndrome is the most common iden-
tified c\buse of ment\bl ret\brd\btion. We h\bve
described clinic\bl \bnd psychomotor follow-up
from 1990–2004 in 322 Sicili\bn children with
Down syndrome. Medic\bl m\bn\bgement of the
syndrome requires c\breful \bssessment, mo-
nitoring, prevention\v \bnd vigil\bnce.
Key-word: Down syndrome, follo\vw-up
Introduction
Down syndrome (DS) rem\bins the most fre-
quent single c\buse of\v ment\bl ret\brd\btion.
The prev\blence \bt birth h\bs recently decre\b-
sed from one in 700 to\v \bbout one in 1000
1).
As \b result of the ch\bnges in the pr\bctice of
medic\bl c\bre, the lif\ve expect\bncy in DS h\bs
improved r\bdic\blly in the p\bst few dec\bdes
2).
The medi\bn \bge of de\bth h\bs incre\bsed \bnd
the \bver\bge life expect\bncy in persons with
DS h\bs recently been prolonged to 49 ye\brs
of \bge
3).
Medic\bl m\bn\bgement of the syndrome re-
quires \bn org\bnised \bppro\bch of \bssessment,
monitoring, preventi\von \bnd vigil\bnce.
At the P\bedi\btric \bnd Intensive Ther\bpy De-
p\brtment for the newborn of the University
of P\blermo 322 subjects (166 m\bles \bnd 156
fem\bles) from Sicily \bre under \b follow-up
progr\bmme from birt\vh to 18 ye\brs of \bge.
The follow-up consists of \b periodic \bppr\bi-
s\bl of the he\blth of the DS child (\buxologic\bl
\bnd psychomotor follow-up) \bnd \b clinic\bl-di-
\bgnostic progr\bmme for recognising the di-
se\bses most frequentl\vy \bssoci\bted with DS
(congenit\bl m\blform\btions, \butoimmune dis-
e\bses, etc.)
It is therefore necess\bry to know the n\btur\bl
history of DS, the medic\bl complic\btions oc-
curring \bnd their prev\blence \bt different \bges.
Epide\biology
Both neon\bt\bl \bnd inf\bnt mort\blity were sig-
nific\bntly higher in the DS children th\bn in the
gener\bl popul\btion. The mort\blity h\bs f\bllen in the p\bst few ye\brs. Between 1978 \bnd
1984 in It\bly
4)mort\blity occurred in the first
month of life in 7.9%of the c\bses; out of 322
children with DS followed-up from 1990 to
2004, 14 (4.9%) died \bt v\brious \bges: 8/322
(2.5%) of congenit\bl he\brt dise\bse, 2/322
(0.6%) of leuk\bemi\b (one \bcute lymph\btic leu-
k\bemi\b \bnd one \bcute myeloid leuk\bemi\b),
3/322 (0.9%) of severe systemic infections
\bnd one (0.3%) of fet\bl \vhydrope.
Assessment and manageme\/nt
(from birth to 18 ye\brs) ( \bab.1)
C\binica\b diagnosis
and cytogenetic ana\bysis
Although the phenotype is v\bri\bble, \b clinic\bl
di\bgnosis is possible \bt birth in most c\bses
in rel\btion to the ch\br\bcteristic physic\bl fe\b-
tures. Difficulties c\bn \brise in very sm\bll b\b-
bies, \bs in the c\bse with prem\bture or sm\bll-
for-\bge newborns, or if there \bre severe cli-
nic\bl problems th\bt turn the \bttention \bw\by
from the phenotypic ch\br\bcteristics of the in-
f\bnt.
In our experience most c\bses 319/322 (99%)
h\bve been di\bgnosed in the first month of life
The chromosome \bn\blysis in 309/322 (96%)
showed \b st\bnd\brd trisomy 21 origin\bting
from \b non-meiotic chromosome disjunction,
in 9/322 (2.8%) \b trisomy from unb\bl\bnced
robertsoni\bn tr\bnsloc\btion [of which the
most frequent is the 14/21\bnd in 3/322,
(0.9%) t21;21], «de novo» in 78% of c\bses,
\bnd in 4/322 (1.2%) there w\bs \b mos\bi\vc tri-
somy with the presence of two cellul\br lines
(cells with norm\bl k\bryotype \bnd cells with
trisomy 21). In c\bses of tr\bnsloc\btions, the
risk of h\bving \bnother newborn with Down
syndrome is rel\bted to the occurrence in one
of the p\brents of \b \vb\bl\bnced tr\bnsloc\btio\vn.
Communication of the\/ diagnosis
The communic\btion of the di\bgnosis is, per-
h\bps, the most delic\bte moment of the whole
follow-up period of the child with Down syn-
drome \bnd it must be done in two st\bges: when the di\bgnosis is suspected \bnd when
it is confirmed.
C\binica\b and instrumen\/ta\b
investigations for con\/genita\b
ma\bformations
Congenit\bl he\brt dise\bse is the most com-
mon \bnd severe m\blform\btion: \bbout 50% of
newborns \bre \bffected
5).
In our experience congenit\bl he\brt dise\bse
w\bs found in 135/322 (42%) c\bses: in 55/
135 (41%) \btrioventicul\br sept\bl defect, in
43/135 (32%) ventricul\br sept\bl defect; in
16/135 (12%) secundum \btri\bl sept\bl defect,
in 11/135 (8%) persistent p\btent ductus \br-
teriosus, in 8/135 (6%) tetr\blogy of F\bllot \bnd
in 2/322 (0.6%) other l\vesions.
All newborn b\bbies with Down syndrome
must be submitted to \bn echoc\brdiogr\bm by
\b p\bedi\btric c\brdiologist, even in the \bbsen-
ce of symptoms
6).
Congenit\bl or\bl-g\bstrointestin\bl tr\bct m\bl-
form\btions were frequent (7.3%)
7). In 322 Si-
cili\bn children with DS congenit\bl g\bstroin-
testin\bl tr\bct m\blform\btions were identified
in 17 p\btients (5.2%). The most frequent \bno-
m\blies were: duonden\bl stenosis in 4/322
p\btients (1.2%); congenit\bl meg\bcolon in
4/322 (1.2%); \bn\bl \btresi\b in 3/322 (0.9%),
oesoph\bge\bl \btresi\b in 3/322 (0.9%), cleft
p\bl\bte in 2/322 (0.6%) \bnd di\bphr\bgm\btic
herni\b in 1/322 (0.3%).
Cryptorchidism w\bs found in 28/166 (17%)
m\bles subjects.
Auditory screening
Since sensory defects \bre frequent in Down
syndrome 8), \bll the newborns w\vith Down syn-
drome must be submitted to investig\btions of
the \buditory \bbility (oto\bcustic emission \bt
birth \bnd/or br\binstem \buditory evoked res-
ponse \bt 3 months). In 4/322 (1.2%) congenit\bl
sensorineuron\bl de\bfness w\bs discovered. A
ch\br\bcteristic serous otitis c\bn develop in the
first ye\brs of life \bnd c\bn often persist throug-
hout \bdulthood. A preventive \bppro\bch to the
he\bring problems of \vchildren with DS seems
therefore of the utmost import\bnce in order
to help them to \bcquire \b good communic\b-
tion \bbility \bnd s\bt\visf\bctory soci\blis\btion.
Ophtha\bmo\bogica\b disor\/ders
Red reflexes should be \vchecked \bt birth, \bs
their \bbsence is \bn import\bnt clinic\bl sign of
congenit\bl c\bt\br\bct (15%)
5). In the Sicili\bn chil-
Clinical and psycho\botor follow-up
fro\b 1990 to 2004 in 322 sicil\sian
children with Down syndro\be
M. Piccione, C. Lo Giud\vice, M. M\brtines, L. Gr\bzi\bno, G. Corsello\v
33
Vol. 16 No. 2 2005 Fortbildung / Formation continue
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.
Fortbildung / Formation continue
34
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
Vol. 16 No. 2 2005 Fortbildung / Formation continue
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
References1)Roizen N, Patterson D. 2003. Down’s syndrome. Lan-
cet 361: 1281–1289.
2)Frid C, Drott P, Otterblad Olausson P, Sundelin C and
Annerén G. 2004. Maternal and neonatal factors and
mortality in children with Down syndrome born in
1973–1980 and 1995–1998. Acta Paediatr 93:106–
112 .
3)Yang Q, Rasmussen SA, Friedman JM. 2002. Morta-
lity associated with Down’s syndrome in the USA from
1983 to 1997: a population-based study. Lancet 359:
1019–25
4)Mastroiacovo P, Bertollini R, and Corchia C. 1992. Sur-
vival of children with Down syndrome in Italy. Am J
Med Genet 42: 208–212.
5)American Academy of Pediatrics Committee on Ge-
netics. 2001. Health supervision for children with
Down syndrome. Pediatrics 107: 442–449.
6)Cohen WI. 1999. Health care guidelines for individu-
als with Down syndrome: 1999 revision. Down Syn-
drome Quar 4: 1–15.
7)Frid C, Drott P, Lundell B, Rasmussen F, Anneren G.
1999. Mortality in Down’s syndrome in relation to con-
genital malformations. J Intellect Disabil Res 43 (Pt3):
234–241.
8)Roizen N. 1997. Hearing loss in children with Down’s
syndrome: a review. Down Syndrome Quar 2(4): 1–4.
9)Girodon F., Favre B, Couillaud G, Carli Pm, Parmeland
C, Maynadié M. 2000. Immunophenotype of a tran-
sient myeloproliferative disorder in newborn with tri-
somy 21. Cytometry 42: 118–122.
10)Groet J, McElwaine S, Spinelli M, Rinaldi A, Burtscher
I, Mulligan C, Mensah A, Cavani S, Dagna-Bricarelli F,
Basso G, Cotter FE, Nizetic D. 2003. Acquired mu-
tations in GATA1 in neonates with Down’s syndrome
with transient myeloid disorder. Lancet 361: 1617–
1620.11)Goldacre MJ, Wotton CJ, Seagroatt V, Yeates D. 2004.
Cancers and immune related diseases associated
with Down’s syndrome: a record linkage study. Arch
Dis Child 89: 1014–1017
12)Hasle H, Clemmensen I H, Mikkelsen M. 2000. Risk
of leukaemia and solid tumours in individuals with
Down’s syndrome. Lancet 355: 165–169.
13)Tuysuz B, Beker DB. 2001. Thyroid dysfunction in chil-
dren with Down’s syndrome. Acta Paediatr 90: 1389–
1393.
14)Anwar AJ, Waker JD, Frier BM. 1998. Type I diabetes
mellitus and Down’s syndrome: prevalence, ma-
nagement and diabetic complications. Diabet Med;
15: 160–163
15)Book L, Hart Allison, Black J, Feolo M, Zone JJ, and
Neuhausen SL. 2001. Prevalence and clinical cha-
racteristics of celiac disease in Downs syndrome in
U.S study. Am J Med Genet 98: 70–74.
16)Goldberg-Stern H, Strawsburg RH, Patterson B, Hick-
ey F, Bare M, Gadoth N, Degrauw TJ. 2001. Seizure fre-
quency and characteristics in children with Down syn-
drome. Brain Dev 23: 375–78.
17)Rubin SS, Rimmer JH, Chicoine B, Braddock D, McGu-
ire DE. 1998. Overweight prevalence in persons with
Down syndrome. Ment Retard 36:175–81.
18)Piro E, Pennino C, Cammarata M, Corsello G, Greci A,
Lo Giudice C, Morabito M, Piccione M, Giuffrè L. 1990.
Growth charts of Down syndrome in Sicily: evaluation
of 382 children 0–14 years of age. Am J Med Genet
7: 66–70.
Weitere Informationen
Autoren/Autorinnen
Prof. Giovanni Corsello , Direttore Clinica Pediatrica U.O. Pediatria e Terapia Intensiva Neonatale Dipartimento Materno-Infantile Università di Palermo
