Article published online: 2021-07-26

Original Article 53

Clinical Profile of Indian Children with Down Syndrome

Inusha Panigrahi1 Yogita Bhatt1 Shivani Malik1 Parminder Kaur1 Anupriya Kaur1

1 Department of Pediatrics, Genetic-Metabolic Unit, Advanced Address for correspondence Inusha Panigrahi, MD, DM, Department
Pediatric Center, Post Graduate Institute of Medical Education & of Pediatrics, Genetic Metabolic Unit, Advanced Pediatric Center, Post
Research, Chandigarh, India Graduate Institute of Medical Education & Research, Chandigarh
160012, India (e-mail: inupan@yahoo.com).
J Pediatr Genet 2023;12:53–57.

Abstract This retrospective study was performed on 208 patients with Down syndrome (DS)

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from heterogeneous ethnic population and admitted under Genetics Metabolic Unit.
Keywords The aim of the study was to look for phenotypic variability and associated complica-
► aneuploidy tions in children and adolescents with DS. The average age of the evaluated DS patients
► atrioventricular septal was 34 months. Cardiac anomalies were found in 128 (62%) of the 208 cases. Among
defect the cardiac disorders, atrial septal defects accounted for 30% of cases. Other
► double aneuploidy complications observed were hypothyroidism and developmental delay in around
► karyotyping 31% cases and neonatal cholestasis in 14% cases. Also, we report two cases with Moya-
► trisomy 21 Moya disease and one case with atlanto-axial dislocation.

Introduction In present article, we describe the comorbidities observed

in patients with DS presenting to a tertiary care center in a
Down syndrome (DS) is the most common chromosomal developing country.
disorder leading to intellectual disability.1–4 About 95% of DS
cases are caused by full chromosome 21 trisomy resulting from
Materials and Methods
meiotic nondisjunction, 2 to 3% are caused by Robertsonian
translocation between acrocentric chromosomes such as 13, This is a retrospective observational analysis performed on
14, 15, 21, and 22, while the remaining 2 to 3% are due to DS patients diagnosed, evaluated, managed, and followed up
mosaicism. The risk of having a child with trisomy 21 increases in genetic and metabolic unit of a tertiary care center. The
with maternal age, especially after 30 years of age. center caters to at least six northern territories in India
Approximately, 1 child in 850 live births is born with DS.2 namely Punjab, Haryana, Himachal Pradesh, Chandigarh,
The clinical phenotype seen in DS includes flat facies, Uttar Pradesh, and Jammu and Kashmir. The analysis was
upslanting palpebral fissures, epicanthic folds, brachyceph- performed on 208 DS patients admitted between Janu-
aly with a flat occiput, hypotonia, short stature and a short ary 2018 and September 2020 after taking clearance from
neck, flat nasal bridge, single palmar crease, protruding the Departmental Review Board (DRB, no. 02–21). Informed
tongue, sandal gap, clinodactyly, brachydactyly, microceph- consent was taken from legal guardians of the patients,
aly, small ears, open mouth, and squint and umbilical her- mostly parents.
nia.3 Postnatal diagnosis can be made by karyotyping or The demographic details name, age, sex, and dysmorphic
sometimes by fluorescent in-situ hybridization. A thorough features were noted on a predesigned data collection form. The
knowledge of the associated problems and issues helps in clinical presentation, complaints at admission and complica-
better management of DS patients. The management of DS tions in form of failure to thrive, cardiac, endocrinological,
include holistic approach with nutritional rehabilitation, gastrointestinal complications, hearing, and speech and vision
physiotherapy, speech therapy, and occupational therapy abnormalities were recorded for each case.
as well as treatment of associated complications like cardiac Head circumference, weight, and height were evaluated
disease, hypothyroidism, celiac disease, and infections.5 and recorded. This anthropometric data were used to assess

received © 2021. Thieme. All rights reserved. DOI https://doi.org/

February 9, 2021 Georg Thieme Verlag KG, 10.1055/s-0041-1732475.
accepted after revision Rüdigerstraße 14, ISSN 2146-4596.
June 15, 2021 70469 Stuttgart, Germany
article published online
July 26, 2021
54 Down Syndrome in India Panigrahi et al.

Fig. 1 Age distribution of the patients of Down syndrome in present

study (total n ¼ 208, male ¼ 134, female ¼ 74).

the nutritional values of the children and was expressed in Z-

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score terms. Fig. 2 The spectrum of cardiac anomalies in 145 children with Down
syndrome.

Results
mental delay in 31%, and seizures in 2.4%. Additionally, we
Out of a total of 208 patients, 134 were males (64.4%) and 74 report two cases with Moya-Moya disease and 1 case with
females (35.5%; ►Fig. 1). Most of the DS patients were in the atlanto-axial dislocation (►Table 1). Among the cardiac
0 to 5 years of age group (i.e., 179, including males and complications, atrial septal defects were found to be the
females). Average maternal age was 29 years in the cohort. most common with the associated heart conditions are
Analysis of head circumference, weight, and height was summarized in ►Fig. 2.
performed for the children. In relation to weight and height, We present here four illustrative cases admitted in the
114 children (58.8%) presented with low weight and 48 genetic ward of the center:
children (23.07%) with low height while 74 cases (35.57%)
• Case 1: A 1-month-old male born at term was admitted to
with microcephalic. All cases included in the study were
our ward with complaints of respiratory distress since
diagnosed postnatally. Hypotonia was found to be the com-
birth. His birth weight was 2.8 kg. On examination, the
mon clinical feature with cases 137 (65.86%) followed by
child had systolic murmur, suspicion of heart disease with
other features as summed in ►Table 1. Karyotyping was
cardiac failure, and pneumonia. His respiratory rate was
performed in all cases and trisomy 21 was found in 203 cases
72/min and he had features of DS including the typical
(97.6%), while translocation and mosaic were identified in
eyes and low set ears. His Hb was 17 g/dL and white blood
five (2.4%) cases. In associated complications, cardiac defects
cell was 15,170/mm3. The renal function tests revealed
were found in 62% of cases, hypothyroidism in 30.28%,
blood urea (13 mg/dL) and normal serum creatinine. On
central nervous system (CNS) problems in form of develop-
day 3 of ward stay, the child developed worsening

Table 1 Clinical features and complications in children with Down syndrome in present study (n ¼ 208)

Clinical manifestations n % Clinical manifestations n %

Hypotonia 137 65.9 Failure to thrive 114 54.8
Poor feeding 7 3.36 Stunting 48 23
Constipation 35 16.8 Global developmental delay 66 31.7
Clinodactyly 34 16.3 Cardiac 128 61.5
Microcephaly 74 35.57 Celiac disease 3 1.44
Brachycephaly 22 10.57 Gastrointestinal anomalies 6 2.9
(Hirschsprung/malrotation/ duodenal atresia)
Brachydactyly 18 8.65 Pneumonia 37 17.78
Umbilical hernia 6 2.9 Atlantoaxial dislocation 1 0.5
Thrombocytopenia 8 3.84 Vision abnormalities 4 1.9
Meningitis 6 2.9 Hearing abnormalities 2 0.96
Hypothyroidism 63 30.3 Seizures 5 2.4
Hydronephrosis 1 0.5 Celiac disease 3 1.44
Neonatal cholestasis 29 13.9 Moya-Moya 2 0.96

Journal of Pediatric Genetics Vol. 12 No. 1/2023 © 2021. Thieme. All rights reserved.
 Down Syndrome in India Panigrahi et al. 55

tachypnea, with chest X- ray revealing bilateral infiltrates.

Echocardiography (ECHO) revealed complete AV canal
defect (AVCD), large VSD with OS ASD, right-sided AV
valve regurgitation, and a tiny PDA. Ultrasonography
(USG) of cranium-cerebral hemispheres were normal.
USG KUB showed mild prominence of left renal pelvis
with anteroposterior diameter (APD) of 6 mm. There was
also minimal splitting of bilateral pelvicalyceal system,
and on follow-up USG, the right APD was 2.5 mm and the
left APD was 3.4 mm.
Fig. 3 The karyotype in child with double aneuploidy showing three
• Case 2: An 18-month-old female child born to a non-
copies of chromosome 21 and extra copy of X chromosome.
consanguineous couple, with developmental delay pre-
sented with sudden onset of nonprogressive weakness of showed blood urea/serum creatinine of 16/0.29 units.
the left upper and lower limb with facial deviation toward Thyroid function tests and transglutaminase antibody

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the right side since 4 days. Her birth weight was 1.5 kg. On were normal. An initial possibility of atlanto-axial dislo-
examination, the child had wide open anterior fontanelle, cation was kept. At the time of admission, the child was
facial features including the slanting eyes, saddle toes, neurologically stable with improving left hemiparesis. X-
protruded tongue, simian crease, and left facial nerve ray of craniovertebral junction (CVJ) and computed to-
upper motor neuron palsy. In addition, she had hypotonia, mography scan of the head were grossly normal. MRI
and decreased power in left upper and lower limbs. Head brain with spine shows atlanto-axial subluxation with
circumference was 41.4 cm, consistent with microcepha- fracture or unfused odontoid process, displacement with
ly. The possibility of DS phenotype with acute ischemic associated ligamentous injury with spinal canal stenosis.
stroke, possibly Moya-Moya disease versus embolic Repeat X-ray of CVJ lateral view showed persistence of
stroke was considered. atlanto-axial subluxation with fracture odontoid process
with displacement, and she was referred to surgical
On routine investigations, Hb was 7.8 g/dL, WBC of 9530/ management.
mm3, and normal renal function tests. The child had one • Case 4: A 7-month-old male child presented with fever and
episode of generalized tonic-clonic seizures on day 2 of her cough for 5 days. The child was put on oxygen therapy, IV
hospital stay which lasted for <1 minute. Magnetic reso- antibiotics, and furosemide. After 5 days, the oxygen re-
nance imaging (MRI) of the brain showed multiple patchy quirement decreased, and antibiotics were also stopped. He
subacute infarcts in bilateral parietal lobes (R > L) in deep had undergone PDA ligation earlier and he had the typical
watershed zone and right gangliocapsular region. Gyral facial features of DS; his hands showed brachydactyly,
altered signal intensity in right frontotemporal lobe and short second phalanges of digits, and extra creases over
insula was observed, which as due to ischemia. MR angiog- the thumb. Karyotype done showed 48, XXY, þ 21 (►Fig. 3).
raphy was suggestive of Moya-Moya pattern. Physiotherapy
was initiated. There was gradual improvement in power of
Discussion
both upper and lower limb. Other causes for the stroke were
evaluated. ECHO showed structurally normal heart with Three types of chromosomal aberrations may result in DS.
normal biventricular function. The antinuclear antibody, These include full chromosome 21 trisomy (free trisomy),
C3/C4, lipid profile, and coagulation tests were normal, Robertsonian translocation, and mosaicism. In case of free
except for elevated triglycerides. Ophthalmological evalua- trisomy which is present in majority (>97%) of DS cases is
tion was normal. Hearing assessment could not be done due due to improper segregation of chromosomes during meio-
to presence of ear wax. At discharge, power of both upper and sis, and advanced maternal age is an important risk factor. In
lower left limbs was three-fifths. our study, most mothers were below 35 years of age at birth
of their DS child. Several studies observed advanced mater-
• Case 3: A 3-year-old female child admitted to our ward nal age as an increased risk factor. In a study conducted in
with chief complaints of fall on ground 3 days back while Brazil >90% cases were of free trisomy. We found 98% cases
playing. She had paucity of movements in the left upper with free trisomy 21. According to a study from Mumbai,
and lower limb for 2 days, and was not able to sit or stand 83.87% cases were detected with free trisomy.
for 2 days. She was third born to a nonconsanguineous During the 2 years of the study period, 208 DS cases in
couple with birth weight of 3 kg. On examination, respi- which more than one major structural anomalies were evalu-
ratory rate was 26/min and the child had microcephaly ated and documented. In present study, we have observed a
with head circumference of 37 cm (6.65z) and also had higher percentage of associated anomalies. Therefore, patients
inward-downward slant of the eyes, prominent epican- with DS need to be evaluated carefully for all possible associ-
thal fold, depressed nasal bridge, sandal gap, brachyceph- ated major congenital anomalies. The most common findings
aly, flat occiput, short neck, open mouth, and decreased of this study in patients with DS is hypotonia found in 137 cases
tone in all four limbs. On routine, investigations Hb was (65.9%), poor weight gain/failure to thrive in 114 cases (54.8%),
13.3 g/dL, and WBC was 6,600/mm3; renal function tests and microcephaly in 74 cases (35.57%).

Journal of Pediatric Genetics Vol. 12 No. 1/2023 © 2021. Thieme. All rights reserved.
56 Down Syndrome in India Panigrahi et al.

DS children have higher risk of cardiac defect, Hirsch- Earlier Moya-Moya disease has been reported from our
sprung disease, and duodenal atresia.5,6 The incidences of center in DS cases.18 The case 2 described here also had Moya-
cardiac abnormalities in DS patients is approximately 60%, Moya disease. Some disorders with increased prevalence of
according to a study in Brazil and 56.5% of DS children were this problem leading to stroke include DS and microcephalic
presented with cardiac abnormalities in another. Many osteodysplastic primordial dwarfism. Other reasons for pre-
studies to assess the anomalies associated with DS have disposition to stroke on DS include cardiac defect, hypothy-
reported varied results. In previous studies, the anomalies roidism, and hypercholesterolemia. Earlier five cases have
which are most common in DS cases were congenital heart been reported with DS and in addition Graves’ disease and
defect (CHD), the percentage varied from 44.6, 26, and Moya–Moya disease, with mean of 15.6 years age.19
56.5%.7–9 In the present study, a high proportion (62%) of One of the patients with DS in present study also had
DS children presented with cardiac anomalies. This is be- another chromosomal abnormality revealed by karyotyping.
cause our center is a tertiary care facility, and hence, more He had double aneuploidy, DS and Klinefelter syndrome,
severe cases are referred for evaluation and management. which is quite rare. Previously, a child with this form of
Among the cases with cardiac anomalies, the most common double aneuploidy has been described from Brazil, who had

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defects observed were ASD (30%), followed by PDA (23%), AVCD and hydrocele, and died at 11 months of age.20
VSD in 20% AVCD in 10%, TOF in 4%, and pericardial effusion Around 50% of patients will develop thyroid disease by
and other cyanotic heart disease accounted for 3 and 2%, adulthood which includes hypothyroidism and hyperthyroid-
respectively. The high incidence of cardiac disease is not ism. Hypothyroidism is common in infants with congenital
unique finding of our study. High incidence of ASD as the hypothyroidism, unrelated to autoimmune disease.21 Those
most common CHD was also found in a Korean study by Kim with higher TSH levels and low T4 may be worked up for
et al. In the study done on 394 DS infants, they found 56.9% autoimmune cause of hypothyroidism. Management involves
had a CHD.10 ASD was the most common defect accounting levothyroxine in these cases with periodic monitoring.
for 30.5% of DS followed by ventricular septal defect (19.3%), Since significant proportion of patients in the present
patent duct arteriosus (17.5%), and atrioventricular septal study showed failure to thrive or stunting, the management
defect (9.4%). In a recent study from Egypt, the authors has to be focused on better nutritional support for DS
reported heart defects in 36.9% of DS patients.11 In the patients, especially in developing countries. Also, appropri-
Egyptian study, however, VSD was the commonest of the ate periodic monitoring, and symptomatic treatment for the
cardiac defects, seen in around 17%; either isolated or with additional complications especially cardiac defect; that are
additional cardiac anomalies like PDA or ASD. more likely to occur in children with DS can improve ultimate
DS patients are found to have additional anomalies or outcomes and survival in DS.
problems which can lead to morbidity and mortality.12–15
Earlier studies from India have showed that methylene Authors’ Contributions
tetrahydrofolate reductase (MTHFR) hypermethylation and Initial data collection and drafting were done by Y.B. and
CRELD1 gene mutations may contribute to cardiac defects S.M. Editing and suggestions were then done by I.P. PM
and AVCD respectively in DS patients.12,13 The primary was also involved in editing and also in management of
caregivers of DS children can have social and psychological some cases. I.P. was involved in management of patients in
issues, which should also be considered and attended to the ward and also follow-up in the Genetic Clinic. A.K. was
while managing DS children.16 also involved in follow-up evaluation of the patients. All
Additional clinical findings in the DS cases in the present authors read, gave suggestions, and approved of the final
study included 31% with developmental delay, 30% with manuscript.
hypothyroidism, 23% with stunting, and 16.8% with consti-
pation. Anthropometric indices in the present study revealed Conflict of Interest
significant proportion of cases with low weight (58.8%) None declared.
and low height (23.07%) while 74 cases (35.57%) had micro-
cephaly. According to a study in Brazil, low weight was Acknowledgments
noted in 12.3% cases and low height in 16.4% cases.9 The author would like to thank all the residents posted in
Pneumonia/upper respiratory tract infections were seen in the Genetic Metabolic unit, and in Department of Pediat-
77.4% in a Brazilian study, while in present study 37 cases rics for help clinical evaluation and management of the
(7.78%) children presented with pneumonia. Recurrent re- patients.
spiratory problems including pneumonia are more prevalent
in DS patients due to underlying cardiac defect, additional
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Journal of Pediatric Genetics Vol. 12 No. 1/2023 © 2021. Thieme. All rights reserved.