January 4, 2010

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.


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 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.

download pdf [here]


1. Harold Chen, "Down Syndrome", eMedicine, 2009


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.

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