Early Intervention for Mentally Disabled Children Due to Genetic Etiology

¶ … Intervention for Mentally Disabled Children Due to Genetic Etiology

The objective of the study is to study degrees of response to early intervention among intellectually disabled children due to different genetic etiologies and estimating a possible underlying molecular genetics that could serve to modulate the degree of response to early intervention among children of different genetic causes and children of the same genetic cause.

Sampling

The study reported herein is inclusive of 100 cases involving individuals with mental disabilities due to different genetic causes including those of Down syndrome, Prader-Willi syndrome & Silver-Russell Syndrome in addition to controls matched for age (6M-4Y) and sex.

Methodology

Each case was subjected to: (1) comprehensive history including family history and specifically maternal and paternal ages at birth in each case, similar conditions in the family, jobs and exposure to drugs or x-rays; (2) pedigree construction and analysis; (3) evaluation of social status of the family whether it be high-, middle-, or low-socioeconomic status; (3) clinical examination of all body systems with special emphasis on any anomaly; (4) investigations according to each individual case including such as echocardiography, hearing tests (ABR), fundus examination, brain C-T scan, EEG, as well as others; (5) early intervention; and (6) preliminary (pre-test) evaluation of developmental (DA) of all developmental fields including infant-stimulation, cognition, motor, social maturation, and language through use of the Portage developmental charts; and (7) a comprehensive clinic and house-centered Portage program for early intervention and education of the mentally disabled children and their care givers.

Focus of the Study

This program is primarily focused on training of the studied children in their local environment and specifically in the house. The main program idea reverses the emphasis of the mother in the home. This program was implemented in the form of bi-weekly interventional sessions (30-40 minutes for each session) in addition to 3 monthly evaluation sessions. Throughout the early intervention program (2 years), children have been taking brain function stimulants and enhancers in the form of calculated megadoses of multi-vitamins, anti-oxidants, omega 3 polyunsaturated fatty acids, and essential amino acids.

The treatment and care provided to mentally retarded individuals has experienced change and expansion in recent years. Families prior to the 1800s kept children with mental disabilities at home and hidden from the view of the public. After that time state governments built large institutions to house children with mental disabilities and parents were advised by physicians to institutionalize retarded children resulting in few children with mental disabilities having the opportunity to receive education and training.

Participants

This study involved thirty cases with mental disability and 30 controls matching for age and sex. The thirty individuals studied were divided into twenty (20) cases with Down Syndrome (DS) and ten cases with Prader-Willi syndrome (PWS). The Down Syndrome cases were further subdivided according to cytogenetic analysis into 3 subgroups as follows:

(1) group1 -- the non-disjunction (regular) DS cases (n-10);

(2) group2 -- translocation DS cases (n=5); and group3 -- mosaic DS cases (n=5).

The ages of all patients ranged from 6 months to five years. Patients were obtained through referral to outpatient clinics of Children with Special Needs Department and Clinical Genetics Department, National Research Centre (N.R.C.) from 2000-2002. Each case was subjected to the following:

(1) comprehensive history taking;

(2) pedigree construction and analysis;

(3) evaluation of social status of the family;

(4) clinical examination of all body systems;

(5) investigations according to individual case; and (6) laboratory investigations.

Instruments

Prader-Willi cases were subjected to thorough molecular cytogenetic diagnostic approach such as: FISH using SNRPN or other probe in the common deletion region, along with a centromeric probe, and methylation analysis would detect both UPD and imprinting mutations. Diagnosed cases were subjected to:

(1) preliminary (pre-test) evaluation of developmental age (DA) of all developmental fields (i.e. infant-stimulation, self-help, cognition, motor, social maturation, and language), using the Portage developmental charts;

(2) a comprehensive clinic and house centered program for early intervention and education of the mentally disabled child and their care givers; and (3) a final (post-test) evaluation of DA of all developmental fields using the Portage developmental charts.

Background to the Study

It is now recognized by experts that children with mild mental retardation are many times able to develop new skills over time through early intervention and educational services resulting in their ability to function normally in life and to no longer warranting a diagnosis of retardation. All individuals except those who are most profoundly retarded can generally develop their full potential through living in the community as most individuals with mental retardation have the capacity for learning enabling them to advance intellectually and to develop job skills as well as social skills enabling them to fully participate in society. Individuals with mild mental retardation marry, have families and are basically unable to be distinguished from normal individuals in society however, if these individuals are to achieve their full potential as children these individuals require special education and training beginning in infancy and continuing until they establish an adult role in life.

Literature Review

The work of Connolly, Morgan, Russell, and Richardson entitled "Early Intervention with Down Syndrome Children" states findings that intervention during infancy in children with DS "has a positive effect upon development of adaptive and intellectual skills in children with Down syndrome. Further, the findings suggest that intervention facilitates acquisition of early developmental skills." (1980, p.1407)

The work of Mahoney and Fewell (2001) reports a field-based investigation of the effects of two motor intervention approaches on children with DS including neurodevelopemtnal treatment and developmental skills. It is reported that motor functioning was examined at the beginning of the study and following 1 year of motor intervention services. Pre-post comparisons indicated that children made significant changes in their motor development age and quality of movement over the course of intervention. However, it is reported that there was no evidence that motor invention accelerated development or improved quality of movement beyond what could be expected on the basis of maturation. In addition, no differential intervention effects were associated either with children's diagnosis or treatment model. The work of Crimbie and Gunn (1998) reports developmental assessments for two cohorts of children with DS and report that cognitive function was strongly associated with adaptive behaviors. Conclusions of the study state that early intervention studies should investigate "social disadvantages and biological impairment not only as separate issues but as a combination of the two." The work of Hines and Bennett (1996) states that positive changes were noted in a study of the development of children with DS who were exposed to early intervention programs. Connolly, Morgan, Russell and Fulliton (1993) report that the long-term motor, cognitive and adaptive functioning of a sampling of adolescents with Down Syndrome who were involved in an early intervention program when compared to a group who did not experience an early intervention program showed that the group that had experienced the intervention program "had significantly higher scores on measures of intellectual and adaptive functioning than did the children in the comparison group. The EI group subjects did not show the decline typically seen with age in adaptive functioning in individuals with Down syndrome. The work of Fewell and Owelwein (1991) reports a study involving preschool children with DS who were enrolled in the Model Preschool Program for Children and state findings that there were significantly higher rates of development during interventions than when the children entered the program. Gibson and Harris (1988) report pooled findings from 21 early intervention demonstration studies for Down's syndrome infants and children "…yield consistency of short-term benefits in the growth of finer motor skills, simple social repertoire and DQ/IQ scores, but conflicting evidence in support or not of benefits in the gross motor, linguistic and cognitive/academic domains. Support for the tenacity of gains, on follow-up to the early years of primary schooling, is disappointing. It is recommended that: (1) intervention programmers view the key working assumptions and ideological positions governing present practices more critically; (2) intervention curricula reflect the unique biological and behavioral properties of the syndrome, taking into account individual differences which are independent of etiological label; and (3) care delivery systems be based more fully on multidisciplinary collaboration, especially between the health sciences and education fields." The work of Connolly, Morgan and Russell (1984) report having examined the long-term effects of an early intervention program on the motor, cognitive and adaptive functioning of children with Down syndrome. The study compared the group of children with a group of DS children who did not participate in an early intervention program. The children were assessed and findings show that children in the early intervention program "…earned significantly higher scores (p less than .0005, p less than .05) on the measures of intellectual and adaptive functioning than did the children of comparable age who did not participate in an EIP. The children in the EIP did not show the decline typically seen with age in intellectual and adaptive functioning in children with Down syndrome. The children in the EIP were below expected age levels in gross (77.7%) and fine motor skills (58.3%) but had mean fine motor skill levels that exceeded their mean gross motor skill levels (50%). Based on the results, EIPs for children with Down syndrome appear to provide a foundation for subsequent learning and development.

Because Down syndrome children lack muscle tone, a condition termed hypotonia physiotherapy is critical for these individuals in the form of early interventions. Without physiotherapy the Down syndrome child will be "left with weaknesses, odd behaviors, and disfigurements that need not have happened." (Hudson, 2010) Psychological assessments for Down Syndrome children are important for assessing cognitive abilities, adaptive skills and behavior. Functional skills include communication and motor skills as well as self-help skills and socialization skills. (Cicchette and Beeghly, 1990, paraphrased)

Results of the Study

Self-Help

Mean post-test Self-Help field values of total DS cases and groups 2&3, showed a non-significant statistical (P>0.01) increase compared with mean pretest Self-Help field values (P=0.4, 0.86, respectively). On the other hand, Mean post-test Self-Help field value of group 1 DS cases, showed a non-significant statistical (P>0.01) difference, compared with that of pretest Self-Help field (Table 13).

Pearson correlations among the mean pretest developmental fields values showed that Self-Help had a statistically highly significant positive correlation with Social (P=0.000), Motor (P=0.000) and Language (P=0.007) fields, and a statistically significant positive correlation with Cognitive (P=.021) field (Table 14).

Mean pretest Self-Help field values showed a statistically highly significant (P=0.000) positive correlation with those of post-test Cognitive field, and a statistically significant positive correlation with post-test Self-Help (P=.031) and Language (P=.042) fields. Meanwhile, there was a statistically non-significant (P>0.05) correlation between Self-Help field and both Social and Motor fields (Table 15).

Pearson correlations among the mean post-test developmental fields values of DS cases showed that Self-Help had a statistically highly significant (P=.001) positive correlation with Motor field, and a statistically significant (P=.040) positive correlation with Language. Otherwise, there was a statistically non-significant (P>0.05) correlation between post-test Self-Help and both post-test Social and Cognitive fields (Table 16).

Regarding the sex of DS cases, there was a statistically non-significant (P>0.01) increase of mean pretest Self-Help field value of female cases, compared with that of males (Tables 9). Meanwhile, there was a statistically non-significant (P>0.01) decrease of mean post-test Self-Help f2ield value of male cases, compared with that of females (Table 11).

According to social class, there was a statistically non-significant (P>0.01) decrease of mean pretest value Self-Help developmental field of high (n=7) class DS cases, compared with that of middle and low class cases. Meanwhile, there was a statistically non-significant (P>0.01) increase of mean pretest Self-Help value of low class cases, compared with that of middle class ones (Table 10). The post-test mean Self-Help field of high class (n=7) DS cases, showed a statistically non-significant (P>0.01) decrease, compared with that of middle class (n=9) and low class (n=4) cases. On the other hand, there was a statistically non-significant (P>0.01) decrease of post-test mean middle class Self-Help field value, compared with that of the low class (Table 12).

There was a statistically non-significant (P>0.05) correlation between the mean of ages, maternal and paternal ages of DS cases, compared with both pretest and post-test Self-Help developmental field values (Tables 17,18).

Cognition

Mean post-test Cognitive field value of total DS cases, showed a highly significant statistical (P=0.001) increase, compared with that of mean pretest Cognitive field. Meanwhile, mean post-test Cognitive field value of group 2 DS cases, showed a significant (P=0.009) statistical increase, compared with that of mean pretest Cognitive field. On the other hand, mean post-test Cognitive field values of groups 1&3 of DS cases, showed a non-significant statistical (P=0.27, 0.19, respectively) increase, compared with those of mean pretest Cognitive field (Table 13).

Pearson correlations between mean pretest Cognitive field values and those of the other pretest developmental fields, showed a statistically significant positive correlation with Social (P=.045) and self-help (P.021) fields, otherwise, there was a statistically non-significant (P>0.05) correlation with other pretest developmental fields (Table 14).

Mean pretest Cognitive field values had a statistically highly significant positive correlation with those of post-test Cognitive (P=.000) field, and a statistically significant negative correlation with mean post-test Social (P=.019) field value. Meanwhile, there otherwise, there was a statistically non-significant (P>0.05) correlation with other post-test developmental fields (Table 15).

Mean post-test Cognitive field value showed a statistically non-significant (P>0.05) positive correlation with those of the other post-test developmental fields (Table 16).

Regarding the sex of the studied DS cases, there was a statistically non-significant (P>0.01) increase of mean pretest Cognitive field values of female cases, compared with that of males (Tables 9). On the other hand, there was a statistically non-significant (P>0.01) decrease of mean post-test Cognitive field values of female cases, compared with that of males (Table 11).

According to social class, there was a statistically non-significant (P>0.01) decrease of mean pretest Cognitive developmental field of high (n=7) class DS cases, compared with that of middle and low class cases. Meanwhile, there was a statistically non-significant (P>0.01) difference between the mean of pretest Cognitive value of low class cases, compared with that of middle class ones (Table 10). There was a statistically non-significant (P>0.01) increase of post-test mean high class Cognitive field value, compared with those of middle and low classes. On the other hand, there was a statistically non-significant (P>0.01) difference between the post-test mean of Cognitive value of middle class cases, compared with that of low class (Table 12).

There was a statistically non-significant (P>0.05) correlation between the mean of ages, maternal and paternal ages of DS cases, compared with both pretest and post-test Cognitive developmental field values (Tables 17,18).

Motor

Mean post-test Motor field value of total DS cases, showed a significant statistical (P

Pearson correlations between mean pretest Motor developmental field values and those of the other pretest developmental fields, showed a statistically highly significant positive correlation with Social (P=.002), Self-Help (P=.000), and Language (P=.005) fields. On the other hand, there was a statistically non-significant (P>0.05) correlation with Cognition (Table 14).

Mean pretest Motor developmental field values showed a statistically highly significant positive correlation with post-test Motor (P=.004) field. Meanwhile, pretest Motor developmental field values had a statistically significant positive correlation with post-test Self-Help (P=.033) and Cognitive (P=.012) fields, and a statistically non-significant negative correlation with Social field (Table 15).

Pearson correlations among the mean post-test developmental fields values of DS cases showed that mean post-test Motor field value had a highly significant (P=0.001) correlation with Self-Help field. Otherwise, there was a statistically non-significant (P>0.05) correlation between Motor field and Social, Cognition and Language developmental fields (Table 16).

Regarding the sex of the studied DS cases, there was a statistically non-significant (P>0.01) decrease of mean pretest and post-test Motor field values of female cases, compared with those of males (Tables 9,11).

According to social class, there was a statistically non-significant (P>0.01) decrease of mean pretest Motor developmental field of high (n=7) class DS cases, compared with those of middle and low class cases. Meanwhile, there was a statistically non-significant (P>0.01) increase of mean pretest Motor value of low class cases, compared with that of middle class ones (Table 10). There was a statistically non-significant (P>0.01) decrease of mean post-test high class Motor field value, compared with those of middle and low classes. On the other hand, there was a statistically non-significant (P>0.01) increase of the mean post-test Motor field value of middle class cases, compared with that of low class ones (Table 12).

There was a statistically non-significant (P>0.05) correlation between the mean of ages, maternal and paternal ages of DS cases, compared with both pretest and post-test Motor field (Tables 17,18).

Language

Mean post-test Language field values of total and groups 1&2 DS cases, showed a non-significant statistical (P=0.37, 0.26, respectively) increase, compared with those of pretest Language field. Meanwhile, there was a statistically non-significant (P=0.83) difference between mean post-test Language field value and pretest of group 3 DS cases (Table 13).

Pearson correlations between mean pretest Language developmental field values and those of the other pretest developmental fields, showed that showed a statistically highly significant positive correlation with Self-Help (P=.007) and Motor (P.005) fields, and a statistically significant (P=.033) positive correlation with Social developmental field. Meanwhile, there was a statistically non-significant (P>0.05) correlation between Language field and cognition (Table 14).

Mean pretest Language developmental field value showed a statistically significant (P=.011) positive correlation with post-test Cognitive field, otherwise, there was a statistically non-significant (P>0.05) correlation between pretest Language field and post-test Social, Self-Help, Motor, and Language fields (Table 15).

Pearson correlations among the mean post-test developmental fields values of DS cases showed that mean post-test Language field value had a significant correlation with Self-Help (P=.040) and Motor (P=0.027). On the other hand, there was a statistically non-significant (P>0.05) correlation between Language with both Social and Cognitive developmental fields (Table 16).

Regarding the sex of DS cases, there was a statistically non-significant (P>0.01) increase of pretest mean Language field value of female cases, compared with that of males (Tables 9). On the other hand, there was a statistically non-significant (P>0.01) increase of post-test mean Language field value of male cases, compared with that of females (Tables 11).

According to social class, there was a statistically non-significant (P>0.01) increase of pretest mean Language developmental field of high (n=7) class DS cases, compared with that of middle class cases. Meanwhile, there was a statistically non-significant (P>0.01) difference between pretest mean Language value of high class cases, compared with that of low class ones. On the other hand, there was a statistically non-significant (P>0.01) increase of pretest mean Language developmental field of low class cases, compared with middle class ones (Table 10). There was a statistically non-significant (P>0.01) increase of post-test mean Motor field value of high and low classes cases, compared with that of middle class. On the other hand, there was a statistically non-significant (P>0.01) difference the post-test mean Motor field value of high class cases, compared with that of low class ones. (Table 12).

There was a statistically non-significant (P>0.05) correlation between the mean of ages, maternal and paternal ages of DS cases, compared with both pretest and post-test Language field (Tables 17,18).

Correlation of Laboratory findings with developmental fields:

By correlating the different laboratory findings of studied DS cases and their pretest developmental fields values. It was found that Erythrocyte SOD values of DS patients showed a statistically significant negative correlation with the pretest Social field values (P=.023), otherwise, there were no significant (P>.05) correlations between the other different laboratory values and the other pretest developmental fields values of DS patients (Table 19).

1. Patients with Prader-Willi syndrome:

Chromosomal analysis

Molecular genetic analysis for cases with PWS showed that 9 cases (90%) had interstitial deletion of 15q11-13 on chromosome 15 by FISH technique, and one case (10%) had no deletion.

Pedigree analysis

They were six (60%) female and seven (40%) male patients. Positive parental consanguinity was found in six cases (30%). Their maternal ages ranged from 23 to 32 years with a mean of 27+4-year, and paternal ages from 30 to 39 years with a mean of 34.6+3.4-year.

Socio-economic classification

Socio-economic classification of families with PWS patients, using our social status sheet (Fig. 3), showed that two cases (20%) were classified as high level, four (40%) as middle, and four (40) as low.

The results of "Portage" EIP

a) Socialization

There was a statistically non-significant (P=0.18) increase of mean post-test Social developmental field value (70.2+4.98), compared with that of pretest (61.9+18) value (Table 20).

Pearson correlations among the mean pretest developmental fields of PWS cases showed that there was statistically non-significant (P>0.05) correlation between the mean pretest Social field value and the mean Self-Help, Cognition, Motor, and Language (P=0.421, 0.765, 0.410,0.771, respectively) fields (Table 21).

Pearson correlations between pretest Social field and the post-test fields of PWS cases showed that there was a statistically non-significant (P>0.05) correlation between the mean pretest Social field and the post-test Social, Self-Help, Cognition, Motor, and Language fields (P=-0.370, 0.122, 0.175, 0.946,09.449, respectively) fields (Table 22).

There was a statistically non-significant (P>0.05) correlation between mean post-test Social developmental field value and the post-test Self-Help, Cognition, Motor, and Language (P=0.119, 0.818, 0.282, 0.257, respectively) fields (Table 23).

b) Self-Help

There was a statistically non-significant (P=0.14) increase of mean post-test Self-Help developmental field value (56.8+5.25), compared with that of pretest (52.5+72.1) value (Table 20).

Pearson correlations among the mean pretest developmental fields values showed that Self-Help had a statistically non-significant (P P>0.05) correlation with Social, Cognition, Motor, and Language () fields (Table21).

Mean pretest Self-Help field value showed a statistically non-significant (P>0.05) correlation with those of post-test Social, Self-Help, Cognition, Motor, and Language (P=0.370, 0.122, 0.175, 0.946, 0.449, respectively) fields (Table 22).

Pearson correlations among the mean post-test developmental fields values of PWS cases showed that Self-Help had a statistically non-significant (P>0.05) correlation with Social, Cognition, Motor, and Language (P=0.119, 0.577, 0.557, 0.256, respectively) fields (Table 23).

c) Cognition

There was a statistically non-significant (P=0.54) increase of mean post-test Cognitive developmental field value (50.8+6.8), compared with that of pretest (48.8+7.6) value (Table 20).

Pearson correlations between mean pretest Cognitive field values and those of the other pretest developmental fields, showed a statistically non-significant (P>0.05) correlation with Social, Self-Help, Motor, and Language (P=0.765, 0.250, 0.932, 0.226) fields (Table 21).

Mean pretest Cognitive field value had a statistically non-significant (P>0.05) correlation with those of post-test Social, Self-Help, Cognition, Motor, and Language (P=0.427, 0.446, 0.137, 0.730, 0.590, respectively) fields (Table 22).

Mean post-test Cognitive field value showed a statistically non-significant (P>0.05) positive correlation with those of post-test Social, Self-Help, Motor, and Language (P=0.818, 0.577, 0.953 0.893, respectively) fields (Table 23).

d) Motor

There was a statistically highly significant (P=1.92003E-05) increase of mean post-test Motor developmental field value (74.9+11.94), compared with that of pretest (49.6+7.18) value (Table 20).

Pearson correlations between mean pretest Motor developmental field values and those of the other pretest developmental fields, showed a statistically non-significant (P>0.05) correlation with Social, Self-Help, Cognition, and Language (P=0.410, 0.243, 0.932, 0.374, respectively) fields (Table 21).

Mean pretest Motor developmental field values showed a statistically non-significant (P>0.05) correlation with those of post-test Social, Self-Help, Cognition, Motor, and Language (P=0.407, 0.180, 0.561, 0.397, 0.326, respectively) fields (Table 22).

Pearson correlations among the mean post-test developmental fields values of PWS cases showed that there was a statistically non-significant (P>0.05) correlation between Motor field and Social, Self-Help, Cognition, and Language (P=0.282, 0.557, 0.953, 930, respectively) developmental fields (Table 23).

e) Language

There was a statistically non-significant (P=0.79) increase of mean post-test Language developmental field value (40.7+20.22), compared with that of pretest (43.6+21.52) value (Table 20).

Pearson correlations among mean pretest developmental fields values showed that there was a statistically non-significant correlation between Language and Social, Self-Help, Cognition, and Motor (P=0.771, 0.123, 0.226, 0.374, respectively) fields (Table 21).

Mean pretest Language developmental field value showed a statistically highly significant (P=0.006) correlation with that of the post-test Language field. Meanwhile, there was a statistically non-significant (P>0.05) correlation between pretest Language and Social, Self-Help, Cognition, and Motor (P=0.446, 0.581, 0.527, 0.456, respectively) fields (Table 22).

Pearson correlations among the mean post-test developmental fields values of PWS cases showed that there were non-significant (P>0.05) correlations between Language and Social, Self-Help, Cognition, and Motor (P=0.257, 0.256, 0.893, 0.630, respectively) fields (Table 23).

Findings of the Study

'This study analyzed the sociodevelopmental data of the studied DS cases following implementation of the Portage Early Intervention Program, DS cases showed marked increases and improvements in the different five developmental areas of:

(1) social development;

(2) self-help development;

(3) cognition development;

(4) motor development; and (5) language development.

DS children studied demonstrated a more focused attention style while in the play alone with toys situation, these children smiled less and rejected the toys more often. The self-help developmental field demonstrates considerable increase in most DS cases including progression of self-care skills with the implementation of intervention sittings. Down Syndrome children experienced difficulty in making stage-to-stage transitions even when taking their slower developmental pace into account. The Down Syndrome children showed differential performance patterns over a series of trials which suggests that their object conceptual knowledge was not consolidated well. Some Down Syndrome cases did not learn the contingency, although some individual infants did learn the contingency and better performance was shown to be associated with higher Portage cognitive field values. There was marked improvement in almost all the studies of Down Syndrome individuals as well as progress in attaining the usual stages of motor development through the use of physiotherapies and psychomotor exercises and specifically the use of attractive colorful objects with sounds. Down Syndrome individuals in the study showed deficit language-production skills relative to language comprehension and cognitive skills.

Approximately 50% of Down Syndrome cases showed delayed language production during the first year of intervention. With the progress of portage sittings, practically all Down Syndrome cases exhibited productive language deficits relative to mental age progress after 2 years of intervention. Deficits in language production were more pronounced in syntactic skills compared with vocabulary development. While 50% of studied Down Syndrome cases exhibited deficits in vocabulary development, the remainder appeared to be developing vocabulary consistent with their cognitive progression. There were significant developmental field correlations due to the intersection of developed social maturation with self-help, motor, and language and cognition as the master key of information processing and learning for all developmental tasks. PWS, showed non-significant improvements of Social, Self-Help, and Cognition fields that could be attributed to the fact that these cases had older range of ages (3-5 years) and the gap between the expected and the actual developmental and mental ages is wider than that of DS cases, with frequent tantrums, outbursts, obsession convulsive neurosis, autistic behaviors, maladaptive behaviors, and sociopathies.