# Handbook of Genetic Counseling/Mosaic trisomy 21 - Transient Myeloproliferative Syndrome

Mosaic trisomy 21 - Transient Myeloproliferative Syndrome

## Introduction/Contracting

* How has everything been going since your last visit in April?
* Do you have any concerns or questions at this time?
* We wanted to follow T in genetics because there is such a wide variability in characteristics, cognitive abilities and health concerns in children with mosaic trisomy 21 and we want to make certain that any special services or health care needs are being met.
* I am going to first ask questions about his medical and developmental hx. since his last visit in April.
* Dr. Doktour will want to take a look at him
* We can answer questions you might have and discuss what our impression is now at this time.

## Medical History

* Any new medical problems?
* How is he eating? What does he eat? How much?
* Is he still being followed by oncology? What are their expectations for T?
* Any surgeries or hospitalizations?
* Medications
* Review systems briefly to check if any concerns with heart, hearing, eyes, bowel movements or stool, bladder problems, muscle or bone problems (broken bones, muscle weakness), seizures, breathing difficulties or snoring loudly at night, any birth marks or unusual skin findings, allergies.

## Developmental History

* I noted that you feel his development is appropriate for his age.
* I just want to get documentation of when he achieved certain milestones
* Ask about milestones
* Ask what he is currently doing?
* Typical two-year old can
* Put on clothes, but not button
* Use spoon little spilling
* How does he pick up small objects can he use fingers in pincer grasp
* About how many words is he saying
* Is he combining words, how many?
* Following two step directions
* Does he have a tricycle? How does he do on that?
* Is he still receiving services through Baby Watch?

## Psychosocial Considerations and Counseling

* Are you considering having more children?
* I know Counselor1 and Dr. Doktour have gone over this, but do you have any questions about recurrence risks or how mosaic trisomy 21 occurs.
* Acknowledge that it has been a lot to go through
* Childhood illness may increase parents worry and/or overprotective behavior concerning their child
* Assess how their support has been and whether they are getting all the help they need
* Assess whether they are worried about cancer recurrence risks

## Mosaic Trisomy 21

* Occurs in 1-2% of liveborn infants with Down syndrome
* Wide variability in (characteristics) phenotype (ranging from completely normal to full DS phenotype)
* Intellectual development varies also (near normal to severe mental retardation)
* How affected an individual is depends on the tissues involved and the proportion of trisomic cells
* Children with DS have 10-20 fold increase in incidence of leukemia
* Most common is a transient leukemia known as transient myeloproliferative disorder (TMD)
* 7 of 8 families with mosaic trisomy 21 studied it appeared that nondisjunction occurred after fertilization then the cell line with extra copy developed and in 1 there was the presence of a third type of chromosome 21 suggesting it was trisomic embryo that lost one copy in one of cell lines subsequently

## TMD (Transient Myeloproliferative Disorder)

* Clinically indistinguishable from congenital leukemia
* Unique due to spontaneous remission (no chemo)
* Complete clinical recovery in many cases
* often associated with trisomy 21 cell line, but not always associated with clinical signs of Down syndrome
* case report of newborn boy (Bhatt, et al., 1995)
* high white blood count, undifferentiated
* initially thought to be congenital leukemia a form that is usually fatal
* 14 other cases with no phenotypic evidence of trisomy 21
* clinical course ranged from relatively benign to serious ending up in death
* all survivors showed complete resolution without chemo
* extent of mosaicism variable, but there was at least a decrease in percent of trisomy 21 cells and some had complete resolution
* some had constitutional presence of trisomy 21 (4/15) others only 10 had analysis of skin fibroblasts and they showed normal karyotype

## Recurrence Risks Mosaic Trisomy 21

* Parents not likely to be at any higher risk than general population because nondisjunction probably occurred in the developing embryo and not the egg or sperm.
* Their risk may be as high as 1% based on empiric risks for parents with a child with full trisomy 21 (this includes risks for other chromosomal abnormalities such as trisomies 18 and 13 and Klinefelter)
* Uncertainty about whether there will be increased risks to the offspring of individuals with TMD. It is possible for them to have germ cell mosaicism for trisomy 21, which would increase risks for their offspring.

## Risks of Recurrence in Cancer

* Although complete resolution of TMD occurs in most patients with DS, 25% end up developing AMKL within 3 years
* No patient with normal phenotype and trisomy 21 cell line has been described to develop AMKL
* Those with constitutional mosaicism speculated to be at higher risk than those without

## Resources

* Bhatt, S. et al. Transient Leukemia With Trisomy 21: Description of a Case and review of the Literature. Amer. Journal of Med. Gen. 58:310-314 (1995).
* Pangalos, C; Avramopoulos, D; Blouin, J L; Raoul, O; deBlois, M C; Prieur, M; Schinzel, A A; Gika, M; Abazis, D; Antonarakis, S E. Understanding the mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis.
* American Journal of Human Genetics. vol. 54, no. 3 (1994 Mar): 473-81.

## Notes

The information in this outline was last updated in 2002.