Renato Cocchi M.D., Ph.D. (Sociology)
Posted on the Internet on December 2006
Copyright by Renato Cocchi, © 2006
  Reprinted with the permission of Renato Cocchi
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This investigation started from a consecutive series of 510 Down, selected with the exclusion of psychotic subjects. Among the 141 subjects = 27.65 % of the whole sample, who during the first consultation showed protrusion of their tongue, 88 of them (62.41%) had checked the result on this symptom following antistress drug therapy. The investigation on this subsample had the following features: as for gender they were 40 F + 48 M, with M/F = 120; the year of birth ranged between 1973 and 1993; the age at the first examination (in months) was average 40.42 ± 35.39, with 6-183 range; distribution of the chromosomal anomalies: Four mosaicisms = 4.54%; 3 translocations = 3.41%; 80 standard trisomy 21 = 90.91%; 1 only clinical diagnosis = 1.14%; presence of the tongue protrusion: irregular in 4 = 4.65%; Frequent in 84 = 95.45%.
A therapy with antistress drugs lasting average 14.73 months with range: 6-36, got the following results: 72 disappearances of the lingual protrusion = 81.82%; 8 irregular presence = 9.09%; Not varied frequent presence = 9.09%. The result is highly significant (p<0.0001). The gender comparison suggests that there are not any meaningful differences both before and after drug therapy.
The tongue protrusion in the Downs is an aspecific symptom, without any link with the chromosome 21. Probably it is a symptom of an internal metabolic stress with irritability of the hypoglossus nerve nucleus and overstimulation of the genioglossus and ioglossus muscles, with repetition of the tongue protrusion movement, without any apparent purpose.

Key words: Tongue, protrusion, Down syndrome, stress, gender, drugs, antistress, therapy, results.

The protrusion of the tongue is a frequent symptom in the Down syndrome, but it is not exclusive of it. As a symptom, drugs can even elicit it during antipsychotic therapies, but also antidepressant ones, mainly tricyclics. We can find it again in the sclerederma, in the mouth-mandibular dystonias, among which the Meige's syndrome. The tongue protrusion comes by the action of the genioglossus and of the ioglossus muscles.

Although the tongue protrusion in Down syndrome persons is a well-known symptom, in 2004 I did not (by seeking on Google, and on Medline since 1960, key words: Down syndrome, tongue, protrusion) any epidemiological investigation on it. Therefore I did a specific research on its presence in a cohort of 510 subjects (Cocchi, 2004b). A following investigation dealt on the possible relationship between the tongue protrusion and general hypotonicity (Cocchi, 2004c), always in Down persons.

By checking out it again in 2006 (on Google, and on Medline since 1960, key words: Down syndrome, tongue, protrusion, epidemiology), the only specific article I found on Google, was that mine (Cocchi, 2004b).

Since I had already picked even the data on the results on this symptom by the current antistress drug treatment, I decided to evaluate them by this new article.

Materials and methods

This research had its field on 88 clinical cards that refer on Down Ss living their family. I have personally seen them, in my outpatient's clinic, treated them with antistress drugs and I checked up them after at least three months.

During the first consultation I usually noted the presence of the tongue protrusion, and the same symptom I checked up during the following examinations.

From these 88 cards I collected: Gender; Chromosomal diagnoses; The year of birth; The age at the first examination; The presence or not of the tongue protrusion at the first examination; The presence or not of the tongue protrusion at the final checkup; The length of the therapy in months.

I reported the presence of the symptom as irregular (±) or frequent (+), and so I transcribed it.

As for the drug therapy, I am referring on what already published (Cocchi and Lamma, 1988; Cocchi, 1989; Cocchi, 1990; Cocchi, 1991; Cocchi, 1993; Cocchi, 1995; Cocchi 1998; Cocchi, 1999; Cocchi, 2003; 2004a) because it not has any specificity feature against this symptom, whose improvement was a positive side effect not looked for, even if not surprising.

The data so obtained were statistically elaborated as for sex, chromosomal anomaly and age bands and evaluated, when possible, with not parametric tests.

This research follows the rules of the Natural Scientific Method. This one, for understanding us, allowed Galileus Galilei to discover the moons of the Jove's planet, though he was the first theorist of the Experimental Scientific Method (Cocchi, 2004d).


The data coming from the 88 clinical cards have its reports in the following tables.

Tab. 1: Epidemiological data of the investigated sample
No. of Ss    88       100.00%   
Males 48 54.54%
Females 40 45.46%
M/F ratio. 120
Chromosomal siagnosis
Standard trisomy 21 80 90.91%
Mosaicisms 4 4.54%
Translocations 3 3.41%
Only clinical diagnosis 1 1.14%
Average age at first consultation (months)    40.42 ± 35.39
Range 6-183 

As we may see in the Table 1, the M/F ratio kept only a few from reported for Italian Down children Down born alive. Even the distribution of the chromosomal anomalies is into the ranges of variance for Italian sample and international samples.

According to these reasons we may think this sample here investigated as a representative one, at least of the Italian Down population.

It is to observe that the tongue protrusion appeared even in person of 15 years and three months at the first consultation.

Tab. 2. Distribution of the prevalence of the intensity of the symptom "protrusion of the tongue."
   No. of Ss  %
The whole sample 88   100.00  
Irregular presence of the symptom (±) 4 4.54  
Frequent presence of the symptom (+)    84 95.46  

The protrusion of the tongue was in the nearly whole sample as a frequent symptom.

Tab. 3: Comparison of the results before and after drug therapy
   Before the drug therapy       At the last checkup     
Frequent (+) 84 95.46%   8 9.09%  
Irregular (±) 4 4.54%   8 9.09%  
Null (-) 0 0.00%   72 81.82%  
Statistical test    Chi Square = 136.116 with 2 df and p < 0.0001  

The difference between before and after drug therapy, in this sample, is highly meaningful.

Tab. 4: Gender comparisons
  Females Males
No. of Ss, and rates 40 100% 48 100%
Year of birth (range) 1976-1993 1973-1990
Average age at first consultation (months) 35.15 ± 35.67 45.56 ± 34.05
Chromosomal anomalies
Translocations 2 5.00% 1 2.08%
Mosaicisms 1 2.50% 3 6.25%
Only clinical diagnosis 1 2.50% 0 0.00%
Standard trisomy 21 36 44
Statistical test Chi Square = 2.426 with 3 df and p = 0667 NS  
Distribution of the tongue protrusion Before After Before After
Frequent (+) 36=90.00%   3=7.50%   46=95.83%   5=10.42%  
Irregular (±) 4=10.00%   5=12.50%   2=4.17%   3=6.25%  
Null (-) 0=0.00%   32=80.00%   0=0.00%   40=83.33%  
Statistical test (Chi Square) for each gender,
before and after drug therapy
 60.034 with 2 df and p <0.0001    73.160 with 2 df and p <0.0001  
Statistical test (Chi Square) between genders  
both before and after drug therapy.
Before therapy: 1.169 with 2 df and p = 0.558 NS  
After therapy: 1.171 with 2 df and p = 0.557 NS  

For the gender control I did not consider the year of birth and the average age at the first consultation. There is not any meaningful difference as for the distribution of the chromosomal anomalies, while the results in each group are extremely meaningful. Between the two groups, there are not meaningful differences as for the distribution of the presence of the symptom, either before either after the drug therapy. It is therefore much probable that both groups, too divided by gender, belong to the same population.

Tab. 5: Evaluation of the Ss who maintained the tongue protrusion after the drug therapy
No. of Ss 16 100.00% 
Males 8 50.00% 
Females 8 50.00% 
M/F ratio 100
Chromosomal anomalies
Standard trisomy 21 15 93.75% 
Translocations 1 4.25% 
Average age at first consultation (months)   57.56 ± 50.37
Range 6 - 183
Therapy length (months) 20.37 ± 8.02
Range 5 - 34
Scoring of the tongue protrusion Before After
Frequent (+)   16    100.00%    8     50% 
Irregular (±) 0 0.00%  8 50% 

Table 5 points out that either the average age at the first consultation and the length of the drug therapy are greater in the group of Ss where the tongue protrusion did not disappear. In eight of them this symptom decreased, being now irregular when it was frequent.


As I said in the introduction, the tongue protrusion is not an exclusive symptom of the Down syndrome. It may be a side effect of drug therapies with neuroleptics, and tricyclic antidepressants, and found too in the tongue-mandibular dystonias.

For what concerns the subsample of Down Ss with tongue protrusion, where I could do the checkup of the result of the drug therapy, I found the usual male prevalence reduced (120, vs 135 at the birth, as reported by Camera and Mastroioacovo, 1984), however with maintained prevalence.

This is yet higher (120 vs 110.60) than what I counted in the 141 Ss of the first epidemiological research, to which belong even the current 88 Ss (Cocchi, 2004a). Also the average age at the first consultation is smaller, coming of about six months earlier than the age of the sample of the 141 aforesaid Ss. The value of these variations is not clear, now.

It is possible that the parents of the subjects who came to the checkup were even that more motivated. So they were also more directed to looking for some help for the condition of their son or their daughter.

The result of the disappearance of the lingual protrusion in 81.82%, with statistic probability of not random, is surely of great interest. Moreover it is so because such a result was not the purpose of the prescribed drug therapy.

The gender analysis maintained the very high statistic probability of a result not random in both genders. Differently, in the comparison males vs females the respective scores did not result meaningfully either before and after the drug therapy. Also the gender distribution of the chromosomal diagnoses, did not get statistic results meaningfully different.

Therefore the symptom has a high probability to not depend directly from the chromosomal anomaly and neither from the gender of the Ss.

As I said previously (Cocchi, 2004b), on the cause of that symptom we can only suggest some hypotheses.

Given that it appears for the action of the genioglossus and ioglossus muscles, the more probable thing is that both receive unintentional stimulations from the hypoglossal nerve, the XII bilateral cranial nerve, with exclusive motor function. It originates with a series of roots that escape from the bulb, between the pyramid and the inferior olivary structure (Adams and Victor, 1989).

The protrusion of the tongue is one of the first gestures learned by the child of 3-4 weeks of life, for imitation (Abravanel and Sigafoos, 1984). That proves that it is a perfectly developed neuromotory structure and already functional. It seems to exclude that the unintentional tongue protrusion is something that follows disturbs of the same-sided neuronal pathway of one or of both genioglossus and ioglossus muscles. There exist similar events, and the result is a same-side paresis with asymmetry of the protrusion, and consequent lingual atrophy.

The appearance of tongue protrusion during therapies with neuroleptic or antidepressant drugs directs or to a toxicity phenomenon or to overstimulation, not excluding both together. In Down children it is more probable that we are dealing with overstimulation of the hypoglossus nerve nucleus, with unintentional repetition of the tongue protrusion.

For my experiences on the squint in these children ( Cocchi, 1991) this not seems to me an air-built hypothesis.


The sample of 88 Down subjects treated with an antistress drug therapy lasting average 14.73 months, with 6-36 range, did get the following results. Seventy-two Ss had disappearance of the tongue protrusion (81.82%); Eight had irregular presence (9.09%) and eight had frequent presence, not varied (9.09%). This result is statistically much meaningful (p<0.0001). The gender comparison suggests that there are not meaningful gender differences either before either after drug therapy.

The tongue protrusion in Down Ss is an aspecific symptom, without any relationship with the chromosome 21. Probably it is a symptom of internal metabolic stress with irritability of the hypoglossal nerve nucleus. This fact elicits a stimulation excess of the genioglossus and ioglossus muscles, leading to repetition of the tongue protrusion movement, without any apparent purpose.


Abravanel E, Sigafoos AD. Exploring the presence of imitation during early infancy. Child Dev. 1984, 55: 381-392.

Adams RG, Victor M. Principles of Neurology. McGraw-Hill, New York, 1989.

Camera G., Mastroiacovo P.: Epidemiologia della sindrome di Down. In. Ce.Pi.M. (ed): Aspetti epidemiologici, genetici, clinici, riabilitativi e sociali della sindrome di Down. Ce.Pi.M., Genova 1984: 225-230.

Cocchi R. The anticipation of walking in drug treated Down infants: A controlled study. It. J. lntellect. Impair. 1989, 2: 15-19. Posted on internet as

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 surgery. It. J. Intellect. Impair. 1990, 3: 11-16. Posted on internet as

Cocchi R.: Drug therapy of squint in Down syndrome subjects. Result according to the length of drug taking: Report on 125 cases. It. J. Intellect. Impair. 1991, 4: 9-14. Posted on internet as

Cocchi R. Drug therapy in Down's syndrome: A theoretical context. It. J. Intellect. Impair. 1993, 6: 143-154. Posted on internet as

Cocchi R. Study on bike riding in Downs aged 10 or more and treated by drug therapy. It. J. Intellect Impair. 1995, 8: 31-36. Posted on internet as

Cocchi R. Drug therapy of upper respiratory tract infections easiness in Downs: A survey on 328 persons. It. J. Intellect. Impair. 1998, 11: 9-17. Posted on internet as

Cocchi R. Drug therapy of bruxism as modulation of stress answers. It. J. Intellect. Impair. 1999, 12: 3-12. Posted on internet as

Cocchi R. Comparison on balance development in Downs aged from 13-24 to 61-72 months, not pretreated and pretreated with antistress drug therapy. 2003. Posted on internet as

Cocchi R. Drooling (or sialorrhea) in Downs treated with primarily antistress drugs. 2004a. Posted on internet as

Cocchi R. Tongue protrusion in Downs. An epidemiological survey on 510 subjects. 2004b. Posted on in internet as

Cocchi R. Which relationship between tongue protrusion and joint laxity/hypotonia in Downs? An epidemiological investigation on 452 subjects. 2004c Posted on internet as

Cocchi R. The Natural Scientific Method in the contemporary medicine. 2004. Posted on internet internet as

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