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 Table of Contents    
Year : 2018  |  Volume : 60  |  Issue : 4  |  Page : 398-403
Diagnostic algorithm of down syndrome by minor physical anomaly

1 Department of Psychiatry, Murshidabad Medical College and Hospital, Berhampore, West Bengal, India
2 Department of Psychiatry, KPC Medical College and Hospital, Jadavpur, Kolkata, West Bengal, India
3 Department of Dermatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India

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Date of Web Publication28-Nov-2018


Background: Down syndrome, most common chromosomal abnormality leading to intellectual disability is being diagnosed by Karyotyping. Due to cost constraints, parents couldn't afford to do Karyotyping which causes delay in individual and family interventions.
Introduction: Down syndrome has characteristic morphological features. The minor physical anomaly (MPA) are insults which occur in utero during embryonic development mostly in first and early second trimester and persists throughout life.
Material and Methods: 70 karyotyping confirmed cases of Down syndrome (DS), 70 other causes of intellectual disabilities (Other ID) and 70 age matched normal children and adolescents (Average) have been incorporated in the study. The Modified Waldrop's scale (Ismail's 41 item scale) have been applied. Demographic comparison and Decision tree algorithm approach have been analysed by SPSS 25 version.
Results and Discussion: The paternal age of childbirth, maternal age of childbirth, maternal age of marriage (P < 0.001), income (P = 0.026) variables are statistically significant in Down's syndrome group in comparison to other two groups whereas age and birth order are not statistically significant. DS group has more MPA (m = 17.04, SD = 5.462), than other ID (m = 5.93, SD = 2.628) and Average group (m = 1.59, SD = 1.378). Big sandal gap, high arched palate and epicanthus are most common three minor anomalies found in Down syndrome. Region wise scoring shows high significance (P < 0.001) in Global head, eyes, ears, mouth, hands and feet in Down syndrome group. The four anomalies; epicanthus, telecanthus, high-arched palate, and curved fifth finger) thus can be grouped as differentiating anomalies. When clinodactyly (item 27) and high arched palate (item 21) are present together or epicanthus (item 08) and telecanthus (item 09) present together sensitivity of diagnosing the case as Down syndrome is 0.945 with negative predictive value 0.979.
Conclusion: The simian crease which is being considered as common physical anomaly is not specific for Down syndrome. The large scale study is required to extrapolate the above findings but surely it opens new avenue of research.

Keywords: Behavioral abnormalities, correlation, Down syndrome, minor physical anomaly

How to cite this article:
Bhattacharyya R, Sanyal D, Bhattacharyya S. Diagnostic algorithm of down syndrome by minor physical anomaly. Indian J Psychiatry 2018;60:398-403

How to cite this URL:
Bhattacharyya R, Sanyal D, Bhattacharyya S. Diagnostic algorithm of down syndrome by minor physical anomaly. Indian J Psychiatry [serial online] 2018 [cited 2020 Nov 30];60:398-403. Available from:

   Introduction Top

Minor physical anomalies (MPAs) can be defined as the atypical morphological features that are found in approximately 4% of the general population. The MPAs have no serious medical or cosmetic significance to an individual.[1] The diagnostic use of MPA has been discussed in various publications. Researchers have termed minor anomalies as “informative morphogenetic variants,” referred them as “micro signs."[2],[3] Approximately 14%–40% of newborns have one MPA and have 3% risk for an associated major anomaly.[3] Three or more anomalies have been found in <1% of newborns, and these newborns are at a 20% risk for a major malformation.[4] When several specific MPAs are seen together in an individual, they can possibly serve as external markers for underlying genetic disorders. These minor anomalies can result from malformations or structural defects or from disruptions that arise from the destruction of a once normally formed structure.[5]

MPAs are slight deviation in external physical clefts (e.g., low-set ears, high-arched palate, and curved fifth finger). Kraepelin in his descriptions of dementia praecox reported so-called the “sign of degeneracy.” The bodily structures involved in expression of MPAs typically share the same embryonic origin with the brain.[6] In addition to teratogenic causes, a frequently cited cause for the development of MPA is neurological damage that results from either prenatal or perinatal birth complications. The specification of timing of the relevant insults can make a contribution to the understanding of the etiology or causative factor of intellectual disability (ID). For example, critical hand and feet development occur during the 8 weeks of gestation while the development of palatal morphology has a wide temporal window, starting from 6 to 9 gestational weeks, and continues until 16–17 weeks, i.e., spanning 1st and early 2nd trimester.[7],[8] The palmar creases possibly reflect the underlying movement of the hand in the embryo and are often seen in children with some decreased fetal movement. It has been hypothesized that MPA, particularly of the mouth region, can impact behaviors later in life. Once formed, MPAs persist into adult life and are readily detected on simple visual examination of the particular body areas.[9]

A high number of MPA are thought to be a reflection of the disruption that occurs during the first trimester of development when the ectodermal germ layer of the fetus is developing. This tissue layer of the developing human embryo is also responsible for the creation of the central nervous system (CNS); therefore, CNS dysfunctions may be hypothetically detected by the presence of MPA. The development of the CNS is parallel with the development of many of the body's organs.

Several markers of abnormal neurodevelopment have been suggested over the years. These include subtle neurological signs, neuropathological findings, dermatoglyphic signs, and MPA. Therefore, one possibly important clue to the developmental abnormality is the presence of MPA. These slight defects of head, eyes, ears, mouth, hands, and feet represent mild errors of morphogenesis that have early prenatal origin. MPAs have major informational value for diagnostic, prognostic, and epidemiologic purposes. They provide an important clue to specific malformation diagnosis, brain pathology, and timing of pathology.[10]

In the absence of an identifiable syndrome, an increase in MPA has been reported in several groups including newborns, school-aged children, schizophrenic and autistic youngsters, intellectually disabled children, psychoneurotic children, learning-disabled children, speech- and language-impaired children, hyperactive children, and inhibited children.[11],[12],[13],[14] Research seems to indicate that for males there is considerable consistency in the results; however, the finding with females is tenuous at best. It appears that a high number of MPA are evident in several pathological groups of boys, as compared with intellectually average controls. Furthermore, there is also a relationship between a high number of MPA and obstetrical complications.[15],[16],[17]

In the past several decades, researchers have attempted to define etiological factors in childhood psychopathology with specific interest in reliable diagnostic tools including the study of MPAs. For example, about 50% of Down syndrome children have a simian crease, and there is often a gap between 1st and 2nd toes. Brushfield spots are an accumulation of fibrous tissue in superficial layers of iris found in 85% Down syndrome cases in comparison to 24% controls in the Western population;[14] however, this finding is extremely rare in Asian countries. A careful dysmorphology examination is essential for the detection of MPA and because 71% of anomalies are present in the craniofacial area, and the hands, careful attention to these areas can be helpful in diagnosing occult major anomalies.[10]

As these MPAs as a group are typically associated with Down's syndrome and with other major congenital defects, they have been thought to result from chromosomal irregularities or some kind of insult affecting embryological development.

   Materials and Methods Top

Both in Western literature and in the Indian context, many studies have been done about the chromosomal abnormality of Down syndrome that is found by karyotyping. The karyotyping is not feasible in every suspected case of Down syndrome in the existing healthcare facilities in the developing countries such as India. The detection of Down syndrome is important and unfortunately cannot always be based on karyotyping due to the constraint of resources. Therefore, specific objectives of this study are as follows:

  1. To find the incidence of MPA in Down syndrome and to compare these findings with the other causes of ID and intellectually average population
  2. To make region-wise comparison in three groups
  3. To find specific gold standard anomalies that will help to diagnose Down syndrome.

The individuals for this study are 70 karyotypes confirmed Down syndrome cases, 70 non-Down causes of ID controls, and 70 age-matched intellectually average people from the general population. The study design is a cross-sectional survey independently done by the three researchers for each observation.

Study proper

The Ethical Committee approved the study. The standard Indian Council for Medical Research protocol for informed consent has been used. The samples are taken from the Department of Pediatrics and psychiatry of tertiary care setup hospital as well as from various nongovernmental organizations looking after intellectually disabled children. The age-matched control group is taken from the general population from local schools. The raters were blinded and were not allowed to see the karyotyping report. It was only before the analysis for the sake of dividing the sample in appropriate group; the reports were analyzed by the statistician only.

The instruments used in this study are as follows:

  1. Semi-structured pro forma to collect demographic and clinical information from the patients
  2. Modified Waldrop scale.[7],[8]

MPAs are assessed by Modified Waldrop scale consisting of 18 plus 23 additional items.[18] It takes only 15 min with very minimal removal of clothing (shoes and stockings). For practical reasons, visible surfaces, such as head, eyes, mouth, ears, hands and feet regions, are studied. The Waldrop scale is a simple instrument with good inter-rater reliability and inter-scorer agreement. The coefficient of correlation of the scale has been found to be +0.84 in the original study.

Descriptive and inferential demographic statistics have been applied to the data. The total MPA score as per the Modified Waldrop scale (Ismail et al.) has been calculated. By using analysis of variance (ANOVA), initial comparisons for MPA scores both regarding individual items as well as regional grouping have been done.

To predict a diagnosis of Down syndrome by just looking at the MPAs, the tree classification technique has been used.[19] Classification trees are used to predict the membership of cases or objects in the classes of a categorical dependent variable from their measurements on one or more predictor variables. A classification tree is an empirical rule for predicting the class of an object from the values of predictor variables. For each split, each predictor is evaluated to find the best cut point (continuous predictors), or groupings of categories (nominal and ordinal predictors) based on the improvement are compared, and the predictor with the best improvement is selected for the split. The process repeats recursively until one of the stopping rules is triggered.

The specific decision tree technique used in this study is QUEST[20] (Quick, Unbiased and Efficient Statistical Tree). Its advantages include the following:

  1. QUEST uses an unbiased variable selection technique by default
  2. QUEST can easily handle categorical predictor variables with many categories.

The reason for choosing this technique was due to:[19],[20]

  1. Results summarized in a tree are very simple
  2. Tree methods are nonparametric and nonlinear, with no implicit assumption, that the underlying relationships between the predictor variables and the dependent variable are linear
  3. Thus, tree methods are particularly well suited for data mining tasks
  4. Tree methods can often reveal simple relationships between just a few variables that could have easily gone unnoticed using other analytic techniques
  5. Instead of constructing a mathematical function as in discriminant analysis, decision tree creates a hierarchical classification taking individual variables separately according to importance, and a process closely resembling clinical decision-making. Data have been analyzed using the software SPSS 25.00 for Windows (SPSS Inc., Chicago, IL, USA.).

   Results Top

The average paternal and maternal age at the time of childbirth in Down syndrome is 35.76 and 31.16 years, respectively, which corroborates the earlier findings that the incidence of Down syndrome increases with both increase in paternal and maternal age [Table 1]. The maternal age of marriage and income is other significant demographic variables.
Table 1: Descriptive and analysis of variance summary of demographic profile

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The total score of Modified Waldrop scale (Ismail et al.) shows [Table 2] significantly higher values in the Down syndrome group (mean = 17.04; standard deviation [SD] = 5.462) than in the other ID group (mean = 5.93; SD = 2.628) and intellectually average age-matched group (mean = 1.59; SD = 1.378).
Table 2: Descriptive summary of modified Waldrop score in three groups

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The 11 items of Modified Waldrop scale are present in more than 50% of cases in Down syndrome group, and three of them are new in comparison to the original version of Waldrop scale, and they are Frontal Bossing, Nostril anteverted, and Micrognathia [Table 3].
Table 3: Items of Ismail-41 scale which are present in >50% of cases

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Mean scoring of various regions in Down syndrome is significantly higher than the other two (control and intellectually average) groups [Table 4]. The mean region-wise scores are 4.0286 (SD 1.849) for Global Head, 2.3571 (SD 1.404) for the eyes, and 2.671 (SD 1.576) for the ear region. The hand region has a mean value of 2.943 (SD 1.641), and the feet region has the same of 2.429 (SD 1.611). ANOVA findings show that differences exist in region-wise grouping of items (global head, eyes, ears, mouth, hands, and feet) of Modified Waldrop scale in three groups (cases, control, and average) which is highly (P < 0.001) significant.
Table 4: Region-wise scoring of modified Waldrop scale in three groups

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While formulating classification tree technique by SPSS 25 IBM Corp., Armonk, NY, USA. It was observed that when item 27 (curved fifth finger) alone is present, the chance of having Down syndrome increases to 82.9%. When item 27 and item 21 (curved fifth finger and high-arched palate) are present together, the chance of having Down syndrome is 97.7%. In absence of item 27 (curved fifth finger), the chance of having Down syndrome will be virtually 100% if both i08 (epicanthus) and i09 (telecanthus) are present. If all the three items i27, i06 (nostrils anteverted), and i08 are absent, the chance of having Down syndrome will be virtually nil (0%).

These four anomalies (epicanthus, telecanthus, high-arched palate, and curved fifth finger) thus can be grouped as differentiating anomalies [Table 5]. At least, one of the characteristics, four anomalies are present in 98.6% of cases (Down syndrome) and 44.3% in control group (other causes of ID). At least, two of these four anomalies are present in 92.9% of cases and 21.4% of controls. When the three of these four are present, the most significant delineation between the groups can be made. While searching for the presence of three of the four differentiating or influential anomalies, it has been found to be present in 94.7% of cases in Down syndrome group and only 5.3% in the control group. All the differentiating items are present in 31.4% of patients of Down syndrome and only 1.4% of persons with other causes of ID. Therefore, it can be said that more than three of these four differentiating anomalies virtually favor the diagnosis of Down syndrome. Thus, an attempt can be made to set diagnostic criteria of Down syndrome by MPA if the three of these four differentiating anomalies are present. An alternate set of criteria for screening can be formulated by the presence of either of the following:
Table 5: Proposed operational criteria for Down syndrome

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  1. i27 (Clinodactyly) and i21 (high-arched palate) are present together

  2. Or

  3. i08 (Epicanthus) & i09 (Telecanthus) are present together.

The alternate criterion yields sensitivity and specificity of 0.945 and 0.884, respectively, with negative predictive value 0.979 which implies that if this criterion is used as a screener non-Down cases can be eliminated successfully in 97.9% occasions. The Kappa value of this alternate set of criteria has found to be 0.762 (0.66–0.859).

The presence of any hidden construct in the scale can be assessed using the principal component analysis (PCA).[21] After running the PCA with varimax rotation, it yields a single-factor solution (only factor to have Eigenvalue of more than 1) which explores 67.317% of the variance of the data. This further confirms that the scale (Modified Waldrop Scale by Ismail et al.) measures a unidimensional concept, the concept of minor anomalies.[7],[8]

   Discussion Top

The three groups (cases, control, and average) are obeying population distribution function, and Streiner factor required to calculate the various statistical tests is 0.36 to fulfill the adequacy of sample size.[21] About 22.84% of patients with Down syndrome also have hypothyroidism, and the only mosaic variety case has relatively higher interquartile and borne by younger mother. The Down syndrome group has significantly more MPA than the other two groups, and most of the MPA is situated in the global head region. This study explores a new dimension about the prevalence of MPAs among the people having ID which needs further studies with larger number of samples. The study also shows the path to formulate operational criteria of MPA to pinpoint possible diagnosis of Down syndrome.

Although simian crease is commonly sought when considering the Down syndrome, these features are not only nonspecific but also occur usually in 50% of cases and, in this study, it is present only in 38.57% of cases of Down syndrome.[12]

The present study has several limitations, for example, the sample size is only modest (n = 70) in each group. The current study probed the internal consistency of the two scales. The Cronbach's α value is higher for the Modified Waldrop scale (0.91) than the original Waldrop scale (0.85). However, some of the physical features are very rare especially in Asian countries. A better scale with wider applicability, reliability, and validity is required to detect MPA in our ethnic background. The metabolic screening has not been done due to administrative inconvenience. The majority of participants are from the urban background. The visceral anomalies are not studied due to cost constraints.

   Conclusion Top

Despite the limitations mentioned above, the study generates relevant information as discussed and it is expected that the results of this study will help further research work regarding the incidence of MPA and correlation of MPA with behavioral abnormalities in the developing countries such as India. Not only the Down syndrome group but also other causes ID group need to be worked out to find whether the MPA can be a predictor of future behavioral characteristics which can have preventive, therapeutic, and rehabilitative and prognostic implications.

It will be preferable if a community-based study can be done to know whether the findings of this study can be projected to the population at large. A closer liaison is required in between the family members, pediatrician, psychiatrists, social workers, and other trained professionals, including the nursing staffs, who provide the first care contacts to detect minor anomalies at the earliest opportunity so that preventive measures can be taken.

The avenue for further research is wide open, and there is a need for large-scale studies to know whether MPA detected in early neonatal period can predict future neuropsychological morbidity so that early remedial action could be taken and early diagnosis can be made. The study also shows the path to formulate operational criteria of MPA to pinpoint possible diagnosis of Down syndrome.

The approach to a child with ID includes the clinical history (including prenatal and birth histories), family history, physical and neurologic examinations, emphasizing the examination for minor anomalies, and behavioral abnormalities that might suggest a specific recognizable syndrome or diagnosis. After this clinical consultation, judicious use of laboratory tests, imaging, and other consultant services can be performed with most patients in a fruitful way.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Correspondence Address:
Dr. Ranjan Bhattacharyya
29, Anandasree, Garia, Kolkata - 700 084, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/psychiatry.IndianJPsychiatry_401_17

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]