MOSAIC FORMS IN DOWN’S SYNDROME:

A SURVEY ON SIXTEEN CASES

Renato COCCHI, a neurologist and a medical psychologist

Abstract

Sixteen mosaic Down syndrome subjects ( F= 5 and M = 11; age at first consultation: 11-228 months, average 107.56) had symptoms analysis to determine if they differ from other DS chromosomal forms. Symptoms or behaviours checked were: delivery and its troubles; food habits, in particular for sweet things and broth and refusal to have breakfast before 9-10 AM; sleep habits and strange postures during sleep; toilet habits; heart anomalies and squint; age at autonomous walking, motor skills, hypotonia , tongue protrusion, hyperkinesis; symptoms of stress or compensatory symptoms (depression or irritability , easiness to respiratory tract infections, bruxism, mouth stimulation, masturbation; other somatic symptoms (a low threshold for hot or cold, abnormal sweating, paleness)eight and weight; language development, socialisation, school achievement, Pervasive Developmental Disorders, typical Down physical features (look).

In this sample it is not possible to find some overall superiority in comparison with other DS forms, but the large extent of peri- and neo-natal troubles could have modified the outcomes.

Key words: Down syndrome, mosaicism, symptoms analysis, physical features.

Italian translation

Down's syndrome

Mental retardation

Symptoms

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Mosaic anomaly among Down's syndrome anomalies stands out in many ways. It is quite rare, by ranging 2-4%, a fact coupling mosaic forms to translocations. Though it is asserted as the only one having its starting point after the conception, being both translocations and pure trisomy 21 gametes' anomalies. Moreover it is the only one that can vary in the rate of trisomic cells.

For these reasons mosaicisms have raised some "logical statements," the main of which is that these forms are less typical Down than the other Down's syndrome's anomalies. The evidence does not always support this view, and many researchers inclined to find new but hardly exaustive variables.

Since these variables did not wholly suffice, then somebodies claimed for a "paradox" instead of getting at a different explanation. The so-called paradox of the mosaicism comes out from the fact that some pure trisomic children look less typically Down than sure mosaic DS children.

This is true and the explanation does not pertain to a possible mistake in chromosome mapping. In other terms, by having a third chromosome 21 in all cells can lead to less "typical" Down features than by having it only in a share of them.

As an attempt to sum up this problem, I decided to do a survey on a sample of mosaic forms from a cohort of 533 Down's syndrome subjects.

Materials and method.

I checked the records of all Down syndrome subjects I saw at first consultation

from January 1979 to May 1966, and I singled out mosaic forms.

From these I collected sex, the year of birth, the age at first consultation, maternal age at birth. Other symptoms or behaviours checked were:

- delivery and its troubles (Cocchi and Branchesi, 1986).

- food habits (Cocchi, 1995) (in particular for sweet things and broth ( Ward, Thanki and Bradford, 1983; Cocchi 1990)) and refusal to have breakfast before 9-10 AM;

- sleep habits and strange postures during sleep (Cocchi, 1989);

- toilet habits (Cocchi 1996);

- heart anomalies (Cocchi, 1990) and squint ( Cocchi and Branchesi, 1986, Cocchi 1991);

- age at autonomous walking (Cocchi, 1989), motor skills (Felicioli and Moretti 1984), hypotonia (Favuto and Cocchi, 1992), tongue protrusion, hyperkinesis;

- symptoms of stress or compensatory symptoms (depression or irritability (Szymanski and Biederman, 1984; Cocchi 1994), easiness to respiratory infections (Cocchi 1981, 1987, 1990), bruxism ( Morse, 1982; Cocchi and Lamma, 1987; Lamma and Cocchi 1988)), mouth stimulation (Cocchi and Tornati, 1976) , masturbation (Cocchi and Ghiglione Rocca, 1977)

- other somatic symptoms (a low threshold for hot or cold (Cocchi, 1989), abnormal sweating, paleness), eight and weight (Cercolani 1988, 1989);

- language development (Felicioli and Moretti, 1984), socialisation, school achievement (Cocchi 1992), Pervasive Developmental Disorders (Cocchi, 1989), typical Down features (look). Data were only processed in plain statistics.

Results

Only 16 records out of 533 (3%) pertained to subjects having mosaicisms. Data collected are shown in tables 1-10.

Table 1: Epidemiological data

S	Sex	Year of birth	Age at 1st visit (months)	Mother's age at delivery (years)
1	f	1986	11	36
2	f	1974	133	33
3	f	1981	57	41
4	f	1979	67	31
5	f	1978	102	28
6	m	1976	133	22
7	m	1973	116	37
8	m	1971	228	26
9	m	1977	110	37
10	m	1977	61	30
11	m	1973	134	38
12	m	1979	108	38
13	m	1984	13	38
14	m	1976	175	39
15	m	1975	179	39
16	m	1978	94	28
Average			107.56	33.75

Table 2: Birth troubles

S	Time: (40 weeks)	Weight at birth (g)	Delivery troubles	Cyanosis or asphyxia	Respirat. distress	Hyper bilirubinemia
1	-4	2680	Caesar. section		yes
2	0	2360	Umbilical cord	yes
			around the neck
3	0	3150	Caesar. section	yes	yes
4	0	2700				yes
5	0	2850		yes	yes
6	0	2980		yes	yes
7	-4	3000	Long lasting			yes
8	0	3600		yes	yes
9	0	3500				yes
10	0	3700	Short lasting	yes		yes
11	0	3700	Dry delivery
12	0	2600				yes
13	0	4200	Induced by drugs	yes	yes
14	0	3850	Caesar. sect.
15	0	4020	Induced by drugs	yes		yes
16	0	3200	Dizygotic twins

To be noted: Only two premature babies, only one low weight at birth, but increased delivery troubles and peri- and neo-natal risk factors.

Table 3: Food habits with particular reference to sweet things and broth, and refusal to have breakfast.

S	F o o d		Sweets	Broth	Breakfast refusal
	preference	refusal
1	unknown	unknown	refusal	unknown	no
2	no	no	scarce	unknown	yes
3	no	all vegetables	normal	increased	no
4	no	raw vegetables	scarce	normal	no
5	no	no	Increased	increased	yes
6	bread	all vegetables	scarce	increased	no
7	no	no	scarce	unknown	no
8	no	no	scarce	normal	no
9	no	no	Increased	normal	no
10	no	milk & all veget.	scarce	normal	yes
11	no	all vegetables	normal	increased	no
12	no	no	Increased	normal	no
13	milk	no	Increased	unknown	no
14	no	all vegetables	Increased	reduced	no
15	milk	all vegetables	scarce	increased	no
16	no	no	normal	normal	no

To be noted in Table 3: Two increased preferences for milk, one refusal for milk; seven refusals for vegetables; eight refusals or scarce liking for sweets, but eleven normal or increased liking for broth; three refusals to have breakfast before 9-10 AM.

Table 4 : Sleep habits, and strange postures during sleep.

S	normal	Difficulty in falling asleep	pavor nocturnus	Type 1 sleep posture	Type 3 sleep posture
1		yes
2		yes
3	yes
4	yes
5	yes			yes
6	yes
7	yes
8	yes				yes
9	yes			yes
10	yes
11	yes			yes
12		yes
13			yes
14	yes
15	yes			yes
16	Yes

To be noted: Only three difficulties in falling asleep, one pavor nocturnus, but five strange postures during sleep.

Table 5: toilet habits

Habit x S

Subject's number

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

Not checked

*

*

*

*

Normal

*

*

*

*

*

*

*

*

Atonic const.

*!

*

*

Spastic const.

*

Diarrheas

*$

*$

! = very atonic; $ = rare

To be noted: Only three Ss with atonic constipation, and only one with spastic constipation.

Table 6: Heart defect, open surgery correction, and convergent squint.

S	Heart defect	Open heart	Days in IC	Squint
		surgery
1	Not reported	yes	5	no
2	no			no
3	no			yes
4	VSD	no		yes
5	no			no
6	no			yes
7	no			no
8	no			yes
9	Not reported	yes	10	yes
11	no			yes*
12	no			no
13	Not reported	yes	8	no
14	no			yes**
15	no			yes
16	no			yes

(*) alternate squint (**) partially corrected by surgery

To be noted: heart defects in 25% and squint in more than 56% (increased).

Table 7: autonomous walking, motor skills, hypotony, tongue protrusion and

hyperkinesis.

S	Age at walking	Motor	Hypotony /	Tongue	Hyper-
	(months)	skills	joint laxity	protrusion	kinesis
1	Not acquired*	normal	yes	yes	yes
2	Unknown	Clumsiness	yes	open mouth	no
3	24	normal	no	no	no
4	23	clumsiness	no	no	no
5	27	normal	no	no	no
6	17	normal	no	open mouth	no
7	Unknown	normal	no	yes	yes
8	18	clumsiness	no	no	yes
9	49	clumsiness	no	no	no
10	Unknown	normal	no	yes	yes
11	Unknown	normal	no	no	no
12	22	normal	no	no	yes
13	Not acquired*	normal	yes	yes	no
14	14	normal	no	no	yes
15	30	clumsiness	no	no	no
16	Not acquires$	troubled$	yes	no	yes

* because too young $ because he has mielodisplasy.

To be noted: Hyperkinesis (43.75%) seems more than what usually reported.

Table 8: symptoms of stress or compensatory symptoms.

S	Depression or irritaility	Reduced immunity	Bruxism	Mouth stimulation	Masturbation
1	no	+	no	no	no
2	yes*	-	yes	no	no
3	yes°	++	no	no	no
4	no	-	no	no	no
5	yes°	++	yes	yes	no
6	asthenia	=	no	no	no
7	yes°	-	yes	yes	increased
8	no	=	yes	no	no
9	yes°	++	yes	no	no
10	yes*	++	no	yes	no
11	yes°	-	no	no	no
12	no	+++	no	no	no
13	yes*	+	no	no	no
14	yes*	-	yes	yes	normal for the age
15	no	-	croaking noise	yes	normal for the age
16	no	-	yes	no	no

Keys: (-) less than normal; (=) normal; (+) moderately increased; (++) markedly increased; (+++) severely increased /// (*) sadness; (°) irritability

To be noted: Depression, as sadness or irritability, is overexpressed; the same happens for bruxism.

Table 9: Other somatic symptoms, heght, weight, overweight.

S	Low threshold for warm / cold	Abnormal sweating	Paleness	Height (cm)	Weight (kg)	Overweight
1	warm	yes	no	68	7.850
2	warm	no	some days	132	28.300
3	normal	no	no	91	14
4	warm	no	no	106	24.200	yes
5	warm	no	some days	109.5
6	normal	no	some days	144	34.200
7	warm	no	some days	126.5	28.700
8	warm	no	no	155
9	warm	no	yes	115	30.450	yes
10	warm	no	some days
11	warm	no	no	133	37.700
12	warm	yes	bef. URTI	121	27.600	yes
13	warm	yes	no	73	8.850
14	warm	no	yes	148	45.000
15	warm	no	no	149	47.750
16	warm	yes	some days	106

To be noted in table 9: A reduced threshold for warm is overexpressed and paleness arises in more than 43%, but few Ss are overweight.

Table 10: language development, socialisation, school achievement, PDD, look.

S	Language development	Socialisation	School achievement	PDD	Down features
1	too young	fairly good	too young		reduced
2	telegraf. type	fairly good	very poor	traits	yes
3	2 years delay	fairly good	preschool		yes
4	2 years delay	good	preschool		yes
5	3 years delay	good	poor		yes
6	nearly normal	good	fairly good		reduced
7	very poor	reduced	very poor	traits	yes
8	poor	fairly good	not at all		yes
9	telegraf. type	good	moderate		yes
10	telegraf. type	fairly good	preschool		yes
11	telegraf. type	good	poor		yes
12	telegraf. type	good	poor		yes
13	too young	timid	too young		yes
14	nearly normal	good	fairly good		yes
15	telegraf. type	fairly good	moderate		yes
16	fairly good	fairly good	preschool	traits	Reduced

To be noted: Although all subjects but two very young use the verbal language, 12 of them out of 14 have marked speech troubles. School achievement seems not different from other Downs, as well as a reduced Down look. Only three out of 16 presented a less evident typical face.

Discussion.

As we can see, features of our sample of mosaic DS do not differ from other forms, as for must investigated symptoms. A supposed chromosomal diagnosis based on these features does not seem feasible, because the equation "reduced trisomic cells as in mosaic forms = reduced typical DS aspect" has too many failures.

The reverse assertion (reduced typical DS aspect = mosaic form) does not match the evidence too.

This problem is only partially afforded by Moeller, 1976, in its survey on 51 reported cases.

Although 25 mosaic DS children demonstrated significantly higher intellectual potential, better verbal facility and less visual perceptual difficulties than 25 pure trisomy 21 matched controls, nothing was reported on physical features.

Their behavioural adjustment and personality characteristics did not differ from those observed in other type of Down syndrome (Fishler, Koch and Donnell, 1976).

Since long time ago, mosaic forms of DS have induced diagnostic problems (Zankl and Rodenwald, 1977), from a clinical point of view. In three mosaic girls, physical characteristics of Down's syndrome were weakly expressed, but hypotonia and hyper-reflexible joints. Developmental milestones were delayed in

all three, with decrease in developmental and intelligence quotients. Only one out of three showed slight mental retardation. (Linne, 1979).

In their recent survey on mosaicism, Fishler and Koch, 1991 asserted that chromosomal analysis is mandatory to confirm or disprove this diagnosis. To have DS children with IQ over 60 at five years of age and relatively normal speech does not necessarily imply to suspect mosaicism.

To speak of a paradox is a derouting way to face the problem. Nature does not make any paradox. We call it so when we are unable to find a more comprehensive explanation of contrasting data.

In facts the symptoms of the Down's syndrome come out from two different mechanisms:

- symptoms directly related to the presence of the extrachromosome 21 (Eg. 150% increasing of the super-oxide-dismutase, because of the presence of three genes controlling it, when normally we have only two);

- symptoms related to metabolic stress due to the presence of a third functioning chromosome, and the subsequent acceleration ("dosage effect") of all the metabolisms the genes of the chromosome 21 control.

Like to any other kind of stress, the body reacts to this one according to its possibilities. These depend on hereditary endowments, and on acquired endowments linked to stress in fetal age, or peri- or neonatal stresses.

They could have modified in a stable way the hyppocampus-cortico-suprarenal feedbacks. As for example, the easiness to upper respiratory tract infections seems related to a cortisol inhibition of nonspecific factors of immunity.

- in this way you can have not only wide phenotypical differences in DS subjects having the same chromosomal anomaly (Eg. pure trisomy 21), but you can have the "paradox" (if you consider it only from the point of view of the chromosomal anomaly) that some mosaic DS children appear more Down than standard trisomic 21 children.

References

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First printed on It. J. Intellect. Impair. 1996, 9: 45-54

Author's address: dr Renato COCCHI, via Rabbeno, 3

42100 Reggio Emilia (Italy).

renatococchi@libero.it

Italian translation

Down's syndrome

Mental retardation

Symptoms

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