Evaluation of mental retardation - Part 2: The factors that elucidate the etiologic diagnosis of the patients with mental retardation or multiple congenital abnormality and mental retardation

Adnan Yuksel; Hulya Kayserili; Gozde Yesil; Memnune Yuksel Apak

doi:10.4103/1817-1745.36763

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ORIGINAL ARTICLE

Year : 2007 \| Volume : 2 \| Issue : 2 \| Page : 53-57

Evaluation of mental retardation - Part 2: The factors that elucidate the etiologic diagnosis of the patients with mental retardation or multiple congenital abnormality and mental retardation

Adnan Yuksel¹, Hulya Kayserili², Gozde Yesil¹, Memnune Yuksel Apak²
¹ Department of Medical Genetics, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey
² Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey

Correspondence Address:
Adnan Yuksel
Yesilyurt cad. Bora sitesi, Ünal apt. No 12, D5, Florya, Istanbul
Turkey

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1817-1745.36763

Abstract

Two thousand nine hundred and seventy-five patients with mental retardation or multiple congenital anomaly and mental retardation (MR or MCA/MR), who were referred to Istanbul University (Departments of Medical Genetics of Cerrahpasa Medical Faculty and Istanbul Medical Faculty) in between 1985 and 2005, were evaluated in order to find out the factors that elucidate the etiology (age at first observation, number and periods of observations and completion of laboratory tests). This is a complementary study of the first part revealing the etiologic classification of MR or MCA/MR patients in our clinics that were performed by 4659 patients. For this part of the study, cases with clinically diagnosed Down Syndrome patients (n: 1179) and neural tube defects (n: 505) were excluded out of the 4659 patients because of availability of diagnosis at first sight. Thus, 2975 patients with MR or MCA/MR were evaluated for the factors that help in the elucidation of the etiologic diagnosis such as age at first observation, number and periods of observations, completion of laboratory tests and the way of diagnosis). The most frequent ages of the MR or MCA/MR patients who were referred for the first time to our genetic clinics were between 1 and 5 years. Moreover, the maximum diagnosis rate was found to be between 1 and5 years of life (50.92%). The ratio of diagnosis at first examination was 27.59% in MR or MCA/MR patients. However, most of them did not attend following examinations (954/2975, 34.31%). From the patients that had a diagnosis, 70.50% of them underwent diagnosis at first examination. The patients who had an etiological diagnosis were mostly examined during 0 to 1 year. Further, a significant number of the diagnosed cases belonged to this group (86.15%). In these patients, 32.67% of undiagnosed cases had incomplete investigation results and 24.83% of them had none of the test results. This quotient was less in diagnosed cases. Etiologically diagnosed 1163 patients were investigated for the method of diagnosis. The results were determined as follows: 459 had a clinical diagnosis (45.48%) and 634 had a specific diagnosis by applying particular laboratory tests (54.51%). This study will be the one of the biggest study in Turkey and also around the world, evaluating the most frequent patient group referred to genetic clinics - MCA or MR.

Keywords: Diagnostic factors, mental retardation, multipl congenital abnormality

How to cite this article:
Yuksel A, Kayserili H, Yesil G, Apak MY. Evaluation of mental retardation - Part 2: The factors that elucidate the etiologic diagnosis of the patients with mental retardation or multiple congenital abnormality and mental retardation. J Pediatr Neurosci 2007;2:53-7

How to cite this URL:
Yuksel A, Kayserili H, Yesil G, Apak MY. Evaluation of mental retardation - Part 2: The factors that elucidate the etiologic diagnosis of the patients with mental retardation or multiple congenital abnormality and mental retardation. J Pediatr Neurosci [serial online] 2007 [cited 2023 Dec 2];2:53-7. Available from: https://www.pediatricneurosciences.com/text.asp?2007/2/2/53/36763

Introduction

Patients with mental retardation, both the isolated and those accompanying with multiple congenital abnormalities, are the most frequently encountered entities in genetic clinics. To date, there have been numerous studies regarding the etiology of mental retardation. ^{[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31]}

The results revealed much variability. It was mostly due to different classification patterns that were utilized. However, with a rapid progression in molecular genetics and cytogenetics and the availability of descriptive cranial and metabolic analyses, etiological and specific diagnoses reached its best.

However, there is a lack of research studies revealing the factors affecting in order to find out the etiologic cause. The aim of this part of the study is to find out the factors affecting the etiology by retrospective evaluation of patients with mental retardation (MR) or multiple congenital anomaly (MCA) and mental retardation (MCA/MR), who were being followed in Departments of Medical Genetics of Cerrahpasa Medical Faculty and Istanbul Medical Faculty.

Materials and Methods

We examined and evaluated 2975 patients as MR or MCA/MR who were referred to our clinic from January 6, 1985 to December 12, 2005. The data of the patients (personal, family history, physical examination, imaging, biochemical and genetic analyses) were recorded.

Some parameters that help to illuminate the etiology, such as age at first observation, number and periods of observations and completion of laboratory tests and the way of diagnosis, were analyzed. On this part of the study of 4659 patients with MR or MCA/MR, 1684 patients who were frequently seen with Down syndrome ( n : 1179) or neural tube defects ( n : 505) were excluded while analyzing these parameters because of the clinical facility of recognition at first sight.

Results

In the previous part of the study, 2847 of 4659 patients with MR or MCA/MR syndromes were diagnosed by clinical, radiological, biochemical and genetic analyses (61.10%). In the group of etiologically diagnosed 2847 patients; the most common disorder was Down syndrome that affected 1179 patients and the second frequent disorder was neural tube defects, which was observed in 505 patients. However, the examination of the factors that elucidate the etiological diagnosis (age at first observation, total number of observations, observation period and completion of laboratory tests) prompted the elimination of these two groups from the study due to availability of diagnosis at first sight.

When Down syndrome and neural tube defects ( n : 1684) were excluded from MR or MR /MCA (n: 4659) groups, the remaining 2975 patients were evaluated according to the factors that affect the etiology. One thousand one hundred and sixty-three patients had an etiological diagnosis. [Table - 1] shows the age of the patients at first observation and whether they had a diagnosis.

We determined that the rate of diagnosis was highest in between 1 and 5 years of age (50.92%) and the least between 0 and 1 year of age (22.44%).

The distribution of MR or MCA/MR patients with or without an etiological diagnosis according to total number of follow-up visits is shown in [Table - 2].

The diagnosis rate in MR or MCA/MR patients at the first examination was 27.5%. The rate tended to decrease on the subsequent examinations. It should be noted that an increase was observed after the fourth examination. The diagnosis rates according to the number of examinations in the MR or MCA/MR groups are shown in [Table - 3].

In majority of the diagnosed cases, the diagnosis was established on the first examination (821/1163, 70.5%). The distribution of the diagnosed and the undiagnosed cases according to observation period in MR or MCA /MR group is shown in [Table - 4].

The diagnosis rate during the first year in the MR or MCA/MR group was 34.01%. The rate was mildly increasing in the subsequent years, and the diagnosis rate of the cases that were examined for over 5 years was estimated to 30.15 %. The age during diagnosis in MR or MCA/MR patients are shown in [Table - 5]. The diagnosis could be established mostly in 1 year after the first referral date (86.15%); 32.67% of the patients who remained undiagnosed did not complete the required laboratory tests and 24.83% of them did not perform any of them [Table - 6].

We have also analyzed the method of diagnosis in etiologically diagnosed patients in MR or MCA/MR group ( n : 1163). 45.48% of them were clinically diagnosed, 54.51% of them were diagnosed specifically by cytogenetic and molecular studies, enzyme analyses and other biochemical tests [Table - 7].

Discussion

The following parameters were counted as the factors that help revealing the etiology: the age during the first referral, number of observations, observation periods and the ratio of completed laboratory tests.

To the best of our knowledge, there has not been such a study to date, analyzing the entire parameters as a group of the factors that helps in revealing the etiologic causes of MR or MCA/MR.

Two thousand nine hundred and seventy-five patients were evaluated in this part of the study. The most frequent range of age for the first referral date to Genetics Clinic was 1-5 years in MR or MCA/MR patients.

Moreover, the diagnoses were performed mostly between these ages (50.92%) [Table - 1]. Both the first referral date and diagnosis rate were the least in frequency at the first year of life (22.44%). The comment on the lower rate is that the specific symptoms seemed to be unclear during first years of life.

Recently, the diagnosis rate of MR or MCA/MR patients has increased uncorrelated by years. This increase has been generated due to an increase in genetic testing and specific molecular testing with easier methods.

The diagnosis rate at first examination was detected to be 27.59% [Table - 2] and a decrease could be seen on repeated examinations. Nevertheless, after the fourth examination, an increase appeared to occur due to the new genetic tests that were conducted and the specific symptoms of the disease that were evident. Most of the patients gave up after the first examination (877/1683, 51.2%). In order to increase the diagnosis rate providing repeated examinations would be helpful for prevention. 70.05% of the patients with a clinical diagnosis had been diagnosed at first examination. This situation proclaimed that most of genetic diseases could be diagnosed at first examination; 29.40% of them had a diagnosis after the first examination. An increase in the examination number lead to a rise of only 5-20% of the diagnosis rate [Table - 2].^[32]

Most of the patients were followed-up for approximately 0 to 1 year. Out of all, the diagnosed cases mostly belonged to this group (86.15%) [Table - 5]. This situation showed that a significant number of patients could be diagnosed with 1-year examination and more than this, thereby increasing the diagnosis rate at 13.85%. Further, it was determined that remaining undiagnosed patients refused routine examinations (1047/1558, 67.2%).

About 32.67% of undiagnosed MR or MCA/MR patients had uncompleted tests and 24.83% had never performed the laboratory tests and imaging [Table - 6]. These values were far less in comparison to the patients who had diagnosis.

When the methods of diagnosis were analyzed in etiologically diagnosed 1163 patients, we found out that 529 of them had a clinical (45.48%) and 634 of them had a specific diagnosis (54.51%) and that the rate was increasing year by year. Diagnosis by cytogenetic analysis played a great role in specific diagnosis with the ratio of 35.68% [Table - 7]. Another similar study had been made by Battaglia et al. , in which physically and mentally retarded 120 patients involved; 97 of them (80.8%) had taken etiological and pathogenetic diagnosis, 19.1% of them underwent diagnosis only by historical and physical examination, 42% of them underwent both clinical and cytogenetic or molecular analysis, 8.3% of them underwent clinical and electroencephalogram (EEG), 7.5% of them underwent clinical and imaging techniques, 1.6% of them underwent only metabolic tests and 0.8% of them underwent other laboratory tests.^[33] In the category of clinical or specific diagnosis, the result of this study strongly correlated by ours [Table - 8].

This study will be the one of the most comprehensive studies both in Turkey and around the world, evaluating the most frequent patient group referred to genetic clinics - MR or MCA/ MR. The specific diagnosis of the patients with MR or MCA/MR will lead to find out the exact mechanisms in disease pathogenesis, thereby providing more relevant information to families about recurrence risk, prognosis, possible treatment options and prenatal diagnosis.

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