Down Syndrome Trisomy 21 (Mongolism) – Causes, Karyotype, Symptoms, Antenatal Diagnosis

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Jul 21, 2011

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Down Syndrome Trisomy 21 (Mongolism) – Causes, Karyotype, Symptoms, Antenatal Diagnosis

Down syndrome, trisomy 21 or the older term mongolism is a condition in which a person is born with certain distinctive features : flat face, short neck, and a degree of mental delay (mental retardation). Although Down syndrome cannot be treated, most patients can lead a normal life. With the proper care and help they need, children with Down syndrome can have a spectacular growth and development and can become healthy and happy adults.

Down syndrome was described in 1861 by Seguin in 1866 by Langdon-Down who specify the clinical features of this syndrome and in 1959, Lejeune specifies the chromosomal etiology.

Down Syndrome

Frequency of Down syndrome is 1.5 per 1000 infants and sex distribution is 3 to 2 for male gender. It is considered that in the occurrence of Down syndrome is involved advanced maternal age, especially over the age of 35. At mothers aged 28 years it is recorded an increased frequency of births with Down syndrome, but this corresponds to a maximum number of births at this age. The risk increases with maternal age, as follows:

Under the age of 30 years, the risk of having a baby with Down syndrome is less than 0.1%;
Between 30 and 40 years, the risk of having a baby with Down syndrome is less than 1%;
Over 40 years, the risk of having a baby with Down syndrome is more than 1%;
Over 45 years, the risk of having a baby with Down syndrome is 3,3%;
Over the age of 50 years, the risk of having a baby with Down syndrome is about 15%.

Down Syndrome Causes And Karyotype

Down syndrome is caused by an abnormal cell division, most often in the ovule before conception or at the moment of conception. Less frequently, abnormal cell division can affect the spermatozoon at the moment of conception. The factors that cause cells to divide abnormally are not known. Genes are grouped in the form of chromosomes. Normally, a child inherits 46 chromosomes, 23 chromosomes from each parent . After the abnormal cell division resulting extra genetic material, usually an extra chromosome. In most cases of Down syndrome, extra genetic material is represented by a extra chromosome 21 , which means that each cell in the body has three copies of chromosome 21 instead of the usual two copies. The extra genetic material disrupts the normal course of development, causing the characteristic features of Down syndrome.

In terms of cytogenetics, Down syndrome can be:

Free and homogeneous trisomy 21 in 92.5% of cases of Down syndrome. These cases are generally cases with de novo appearance, in which is involved maternal age. Karyotype is 47XX+21 or 47XY+21 and the cause is represented by a chromosomal non-disjunction of maternal origin (90%) or a chromosomal non-disjunction of paternal origin (10%).
Mosaic trisomy 21 in 2.5% of cases of Down syndrome. These are sporadic cases, showing karyotype 47XX+21 / 46XX or 47XY+21 / 46XY. Phenotypic manifestations in this type of Down syndrome are more attenuated.
Trisomy 21 with translocation in 5% of cases of Down syndrome. These are cases with de novo appearance, in which is involved a transmission of a paternal translocation. The karyotype is 46XX or 46XY with a translocation between a supernumerary chromosome 21 and, most commonly, a chromosome of group D (pair of chromosomes 13, 14 and 15).
Partial trisomy 21, very rare and is represented by cases of Down syndrome where is an excess of genetic material represented by an extra chromosome 21 which has deletions on q arms.

The study of these cases allow the identification of critical region on chromosome 21 which is responsible for Down syndrome phenotype. This critical region is located on 21q22 band of chromosome 21.

The Clinical Presentation Of Down Syndrome (signs and symptoms)

General Characteristics of Down Syndrome :

Most children with Down syndrome have some of these physical traits:

Short stature : the child usually have slow growth rate, and in adulthood their height is lower than average;
Low muscle tone : a child suffering from Down syndrome may have less muscle strength than other children of the same age;
Short neck, thick with fat and excess skin : usually this feature becomes less obvious as the child grows;
Short and stocky limbs, some children may have a wider space between the thumb and second finger of the foot;
One fold in the central part of the palm : it is called the simian line.

Down Syndrome Facial features:

Ears with modified form : usually small and with a low placement ;
Abnormal mouth and tongue: mouth is often open, exfoliative glossitis, tongue with scrotal appearance (in adolescents and adults), pseudomacroglossia;
Flattened nasal bridge : flat nose portion located between the two eyes (nasal bridge) is frequently clogged;
Brushfield’s spots : colored spots on the iris, these spots are not affecing the sight;
Malformation of the teeth: baby teeth may grow later and in an unusual way, agenesis of lateral incisors.

Down Syndrome Skeleton and skin features: short arm, finger clinodactyly of the fifth finger with a single flexion crease, flat foot, increased space between first toe and second toe, xerosis, hyperkeratotic lesions, alopecia, vitiligo, foliculitis and recurent skin infections.

Psychomotor retardation: hypotonia occurs at birth, but mental retardation is less evident at birth. Children are affectionate, jovial and present difficulty in speech, like the game, arrange objects in order, the memory is not affected. They presents a moderate to sever mental retardation with an IQ = 20-85, with a average of 50.

Down syndrome associates malformations of organs and systems in 45% of cases:

Cardiac: atrioventricular septal defect, ventricular septal defect, interatrial septal defect, patent ductus arteriosus;
Gastrointestinal: duodenal stenosis, anal imperforation, celiac disease, Meckel diverticulm, omphalocele and Hirschprung disease;
Genitourinary: micropenis, cryptorchidism, renal malformations and hypospadias;
Eye: cataracts, astigmatism, myopia, strabismus and glaucoma;
Endocrine: Hashimoto’s thyroiditis, hypothyroidism, hyperthyroidism;
Hematologic: acute lymphocytic leukemia, acute non-lymphoblastic leukemia,
megakaryocytes leukemia;
Immunological: various immune deficiency;
Metabolic: hyperuricemia, diabetes, obesity;
Sterility in males patients with Down syndrome;
Alzheimer’s disease.

Antenatal Down Syndrome

Down Syndrome Antenatal Diagnosis

Antenatal diagnosis of Down syndrome can be done by cytogenetic analysis of amniotic fluid or chorionic villi biopsy, which is done if there is suspicion of Down syndrome by maternal age. Antenatal diagnosis of Down syndrome can be also confirmed by fetal ultrasound.

Genetic consultation:

The risk of recurrence of Down syndrome varies according to karyotype abnormalities. Thus, if homogeneous trisomy 21 exists, then the risk of recurrence is 1% – 2%, and in the case of trisomy 21 with translocation, the risk of recurrence can be up to 20%.