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

Home Page

 

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

Cercolani P.: Il rapporto peso/altezza nel soggetto Down di sesso femminile non trtattato con farmaci: Dati normativi. Riv. Ital. Disturbo Intellet. 1988, 1: 193-198.

Cercolani P.: Il rapporto peso/altezza nel soggetto Down di sesso maschile non trtattato con farmaci: Dati normativi. Riv. Ital. Disturbo Intellet. 1988, 2: 47-52.

Cocchi R.: Susceptibility to infective respiratory diseases in depressed children. Epidemiological survey of 126 subjects, clinical-therapeutic report of 61 cases. Acta Psychiat. Belg. 1981, 81: 350-365.

Cocchi R.: Reduction of susceptibility to upper respiratory tract infections in Down syndrome children following treatment with GABAergic drugs: Report of 70 cases. Int. J. Psychosom. (Philadelphia) 1987, 34/2: 3-7.

Cocchi R.: Hypo-A-GABA-erge Depression bei Kindern. Klinisches Bild und mit neurochemischen Mechanismen verbundene Symptome. In: Friese H.J., Trott G.-E. (eds): Depression in Kindheit und Jugend. Huber, Bern 1988: 126-133.

Cocchi R.: The anticipation of walking in drug treated Down infants: A controlled study. Ital J. Intellect. Impair. 1989, 2: 15-19.

Cocchi R.: A strange posture adopted by Down’s syndrome individuals when sleeping: An epidemiological survey on a cohort of 432 subjects. Ital. J. Intellect. Impair. 1989, 2: 21-24.

Cocchi R.: Psychosis in Down children: An epidemiological and clinical survey on 413 subjects. Ital. J. Intellect. Impair. 1989, 2: 131-136.

Cocchi R.: Sensibilita’ alla temperatura ambientale nei soggetti Down: Una indagine su 432 casi. Riv. Ital. Disturbo Intellet. 1989, 2: 195.199.

Cocchi R.: The use of drugs to modulate stress responses reduces the time of intensive care needed by Down children to recover after open-heart suyrgery. Ital J. Intellect. Impair. 1990, 3: 11-16.

Cocchi R. Facilita’ alle malattie infettive respiratorie nei Down: Indagine epidemiologica su 450 casi. Riv. Ital. Disturbo Intellet. 1990, 3: 131-136.

Cocchi R.: Precursori diretti dell'ac. glutammico e del GABA e abitudini alimentari nei Down: Indagine epidemiologica su 460 soggetti. Riv. Ital. Disturbo Intellet. 1990e, 3: 307-312.

Cocchi R.: Drug therapy of squint in Down syndrome subjects. Results according to the length of drug taking: Report on 125 cases. Ital. J. Intellect. Impair. 1991a, 4: 9-14.

Cocchi R.: School learning in 8 year old Down children treated or not with drugs. Ital J. Intellect. Impair. 1992, 5: 143-148.

Cocchi R.: La depressione nel soggetto Down: Indagine epidemiologica e clinica su 510 casi. Riv. Ital. Disturbo Intellet. 1994, 7: 93-100.

Cocchi R. Food habits in Downs of ten years or more. Ital. J. Intellect. Impair. 1995, 8: 149-157.

Cocchi R.: Toilet habits in Downs: A survey on 492 subjects. Ital. J. Intellect. Impair. 1996, 9: 13-25.

Cocchi R., Bonaduce D.: Suscettibilita' alle malattie infettive respiratorie in bambini psicotici Down e non Down. Riv. Ital. Disturbo Intellet. 1988, 1: 173-178.

Cocchi R., Bonaduce D.: L'autoaggressivita' nel bambino psicotico. Riv. Ital. Disturbo Intellet. 1988, 1: 185-191.

Cocchi R., Branchesi R.: Strabismo e disturbi pre-, peri- e neonatali in soggetti affetti da sindrome di Down. Indagine epidemiologica su 215 casi. Rass. Studi Psichiat. 1986, 75: 504-512.

Cocchi R., Ghiglione Rocca R.: Masturbazione "neurotica" e depressione infantile: Approccio clinico-terapeutico e possibile spiegazione neuropsicologica. Acta Neurolog. (Naples) 1977, 32: 229-241.

Cocchi R., Lamma A.: Bruxism in soggetti affetti da sindrome di Down. Studio epidemiologico su 366 casi. Odontostomat. Implantoprot. 1987, no.4: 66-69.

Cocchi R., Tornati A.: Sintomi di compenso: Loro analisi nella depressione infantile. Rass. Studi Psichiat. 1976: 65: 546-556.

Dosen A.: Depressive conditions in mentally retarded children. Acta Paedopsychiat. 1984, 50: 29-40.

Dorian B., Garfinkel P.E.: Stress, immunity and illness - A review. Psychol. Med. 1987, 17: 393-407.

Favuto M., Cocchi R.: L’ipotonia nel bambino Down: Indagine epidemiologica. Riv. Ital. Disturbo Intellet. 1992, 5: 113-117.

Felicioli F., Moretti A.: Sviluppo motorio, comunicazionale linguistico ed evoluzione dei livelli di apprendimento. In: Ce.Pi.M.: Aspetti epidemiologici, genetici, clinici, riabilitativi e sociali della sindrome di Down. Ce.Pi.M. Genova 1984: 307-342.

Fishler K., Koch R., Donnell G.N.: Comparison of mental development in individuals with mosaic and trisomy 21 Down’s syndrome. Pediatrics 1976, 58: 744-748.

Fishler K., Koch R.: Mental development in down syndrome mosaicism. Am J. Ment. Retard. 199196: 345-351.

Lamma A., Cocchi R.: Drug therapies of bruxism in Down children: Preliminary report. Ital. J. Intellect. Impair. 1988, 1: 19-24.

Linne T.: A prospective psychological and cytogenetic study of three girls with mosaic mongolism. Acta Paediatr. Scand. 1979, 68: 593-597 Moeller D.: Mosaik Mongolismus: Prognose und Beratung. Med. Welt 1976, 27: 244-248.

Morse D.R.: Stress and bruxism. J. Hum. Stress 1982, 8: 34-54.

Szymanski L.S., Biederman J.: Depression and anorexia nervosa of persons with Down Syndrome. Am.J. Ment. Defic. 1984, 89: 246-251.

Ward H.K., Thanki C.M., Bradford H.F.: Glutamine and glucose as precursors of transmitter amino acids: Ex vivo studies. J. Neurochem. 1983, 40: 855-860.

Zankl H., Rodenwald A.: Diagnostiche Probleme beim Mosaik-Down-Syndrom. Klin. Paediatr. 1977, 189: 430-439.

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


Home Page