1. 3 Years old Girl with Mosaic Down syndrome
By: Muhamad Na’im B. Ab Razak
4th Year Medical Student, Universiti Sains Malaysia
3 years old Malay girl with Down’s syndrome come to Pediatric clinic for yearly Medical check-
up. She have classical Down phenotype which are upslenting eye, hypertelorism, flat occiput,
nuchal fold, short neck and gap between first and second toe. She is the only daughter in family
and born to a mother in late 20, full term, spontaneous vaginal delivery with weight 2.2 kg and
good Apgar score. Her father is also in late twenty. Both parents are healthy, and have normal
intelligence. Patient has history of neonatal jaundice secondary to ABO incompatibility and
bronchiolitis. Molecular cytogenic analysis shows karyotype 47, XX +21 (62%) / 46, XX (38%),
mosaic karyotype. FBC for Leukemia screening, Thyroid function test, genetic counseling and
referral to ENT, Ophthalmology and Speech Therapy were offered.
Discussion
Down syndrome is caused by trisomy of all or part of human chromosome 21 (HSA21) and is
the most common genetic cause of significant intellectual disability and occurs in roughly 1 in
800 births. It is firstly described by Down in 1866 and Lejeune and Jacobs et al. independently
determined that Down syndrome is caused by trisomy 21 in 1959.
It is further divided into four types which are Full trisomy 21 (94%), Mosaicism (2.4%),
Translocation (3.3%; 75% De Novo and 25% Familial translocation) and Isochromosome 21.
Mosaicism usually arises after formation of the zygote by non-disjunction at mitosis. However,
majority of it is resulting from trisomic zygote with mitotic loss of one chromosome 21.
The more normal cell in the Mosaic patient, the better phenotype of the patient and lesser degree
of mental retardation. Therefore, most of them can survive by their self and receive normal
education.
K. Mehes reported a case of Down’s syndrome baby with regular trisomy 21 who born to 22
years old mother with normal 46, XX karyotype. The father who is 23 years old was
phenotypically normal with no characteristic of Down's syndrome, had high school qualification,
188 cm tall and active in sports. However, the genetic study showed 46, XY/47, XY, +21
mosaicism.
L.H. Tseng et al has had reported a case of a family with three children who had Down's
syndrome and one healthy child. Cytogenetic studies of the peripheral blood revealed trisomy 21

2. in the affected children, and normal karyotypes in both the parents and the healthy child.
However, a biopsy of the mother's right ovary showed a mosaic trisomy 21 cell line (8/20 cells).
Therefore, it is being proposed that the non disjunction of the oogonia is also responsible for the
recurrent birth with down Syndromic baby. Like the cases proposed by K. Mehes, the affected
mosaic down Syndromic mother has a normal phenotype and intelligence.
In term of complication, patient with mosaic Down syndrome have fever complication especially
congenital heart disease which often shorten the life of Down's syndrome patient. However, the
risk for other fatal disease especially leukemia is still high, about a 20 folds increase. Study by
Lennart Iselius shows that there is over-expressed of leukemia cases in mosaic syndrome
because the infant survived long enough to develop it compared to non dysjunctional Down
syndrome. Therefore, yearly screening for leukemia is beneficial.
Congenital hypothyroidism is about 28 times more common among Down’s Syndromic infants
and 12-fold increased risk of developing infectious diseases, especially pneumonia, secondary to
impaired cellular immunity.
Other complication of down Syndrome includes Sleep apnea, seizure disorder, visual and
hearing impairment, obesity during adolescent, premature aging, behavioral disorder, psychiatric
disorder, umbilical hernia, duodenal atresia or stenosis, TE fistula, Meckel diverticulum,
Imperforate anus, Omphalocele, Renal malformation, Hypospadias, Micropenis, Criptorchidism,
skeletal instability, diabetes, decrease fertility especially in male and skin problems.
In term of prognosis, it is being estimated that 75% of conceptuses die in embryonic or fetal
stage, 85% of infants survive to 1 year and 50% can be expected to live more than age 50 years.
Congenital heart disease is the most significant factor that determines survival. Mortality is also
increase in association with duodenal atresia, infection, Hirschsprung disease and leukemia.
If any of the patient with down Syndrome present with life threatening situation, resuscitation
should not be withdraw and they deserve equal rights to medical access similar to other normal
people.
Reference:
1. Harold Chen, "Down Syndrome", eMedicine, 2009
http://emedicine.medscape.com/article/943216-overview
2. K. Mehes, "Paternal Trisomy 21 Mosaicism and Down's Anomaly", Human genetik 17, 297-300, Springer-
Verlag 1973
3. Lennart Iselius, Patricia Jacobs & Newton Morton, "Leukaemia and transient leukaemia in Down
syndrome", Human Genetic 85:477-485, Springer-Verlag 1990.
4. L.H. tseng et al, "Recurrent Down's syndrome due to maternal ovarian trisomy 21 mosaicism", Archieves
of Gynecology and Obstetrics 255:213-216, Springer-Verlag 1994.
5. Tom Lissauer & Graham Clayden, “Illustrated Textbook of Paediatrics”, 3rd edition, Mosby Elsevier 2007.