**5.2 Syndromes**

## *5.2.1 Downs syndrome*

A second whole or partial copy of chromosome 21 is produced as a result of faulty cell division, which results in the genetic condition known as Downs syndrome. Downs syndrome's physical characteristics and developmental abnormalities are brought on by this excess genetic material.

Individuals with Downs syndrome may have varying degrees of intellectual disability and developmental delays. It is the most prevalent genetic chromosomal defect and the root of children's learning problems. It frequently results in other medical

#### **Figure 10.** *Fetoscopic image of cleft lip—courtesy: JSS MEDICAL COLLEGE, MYSORE.*


#### **Table 1.**

*Syndrome associated with cleft lip and palate.*

issues as well, such as cardiac and gastrointestinal problems. With Downs syndrome, both children and adults have distinctive face features (**Figure 11**) [17].

Though not all people with Downs syndrome have the same features, some of the more common features include the following:

Flattened face Small head Short neck Protruding tongue Upward slanting eye lids (palpebral fissures) Unusually shaped or small ears Poor muscle tone Broad, short hands with a single crease in the palm Relatively short fingers and small hands and feet Excessive flexibility Tiny white spots on the coloured part (iris) of the eye called Brushfield's spots. Short height

This extra genetic material is responsible for the characteristic features and developmental problems of Downs syndrome. Any one of three genetic variations can cause Downs syndrome:

#### *Diagnosis of Dentofacial Anomalies DOI: http://dx.doi.org/10.5772/intechopen.107416*

## **Figure 11.**

*Salient features of Downs syndrome.*

Trisomy 21. About 95 percent of the time, Downs syndrome is caused by trisomy 21—the person has three copies of chromosome 21, instead of the usual two copies, in all cells [18]. This is caused by abnormal cell division during the development of the sperm cell or the egg cell.

Mosaic Downs syndrome. In this rare form of Downs syndrome, a person has only some cells with an extra copy of chromosome 21. This mosaic of normal and abnormal cells is caused by abnormal cell division after fertilisation.

Screening tests during pregnancy

Screening for Downs syndrome is offered as a routine part of prenatal care. Although screening tests can only identify your risk of carrying a baby with Downs syndrome, they can help you make decisions about more-specific diagnostic tests.

Screening tests include the first trimester combined test and the integrated screening test.

The first trimester combined test, which is done in two steps, includes the following:

Blood test. This blood test measures the levels of pregnancy-associated plasma protein-A (PAPP-A) and the pregnancy hormone known as human chorionic gonadotropin (HCG). Abnormal levels of PAPP-A and HCG may indicate a problem with the baby [19].

Nuchal translucency test. During this test, an ultrasound is used to measure a specific area on the back of your baby's neck. This is known as a nuchal translucency screening test. When abnormalities are present, more fluid than usual tends to collect in this neck tissue.

Using your age and the results of the blood test and the ultrasound, your doctor or genetic counsellor can estimate your risk of having a baby with Downs syndrome.

Integrated screening test

During the first and second trimesters of pregnancy, the integrated screening test is administered in two parts. To calculate the likelihood that your child has Downs syndrome, the findings are pooled.

Initial trimester. An ultrasound is used in part one to measure nuchal translucency and a blood test to measure PAPP-A.

First trimester. Alpha fetoprotein, estriol, HCG, and inhibin A are the four pregnancy-related chemicals that are measured by the quad screen in your blood.

Pregnant women's diagnostic procedures

Consider additional testing to confirm the diagnosis if your screening test results are positive or concerning, or if you have a high risk of having a baby with Downs syndrome. You can balance the benefits and drawbacks of these tests with the aid of your healthcare provider.

Diagnostic tests that can identify Downs syndrome include the following:

Sample chorionic villus (CVS). Cells from the placenta are utilised in CVS to examine the foetal chromosomes. Between 10 and 13 weeks of pregnancy, the first trimester is the traditional time for this test to be carried out. A CVS carries a very minimal chance of pregnancy loss (miscarriage).

Amniocentesis. A needle is introduced into the mother's uterus to remove a sample of the amniotic fluid around the foetus. The chromosomes of the foetus are then examined using this sample. After 15 weeks of pregnancy, doctors typically administer this test in the second trimester. A very small risk of miscarriage is also associated with this test.

For couples undergoing *in vitro* fertilisation who are at heightened risk of passing along specific genetic traits, preimplantation genetic diagnosis is a possibility.

Diagnostic tests for newborns

Initial Downs syndrome diagnoses are frequently made based on a baby's looks after delivery. However, babies without Downs syndrome can also have the characteristics linked with the condition, so your doctor will likely request a test called a chromosomal karyotype to confirm the diagnosis. This test examines your child's chromosomes using a blood sample. Downs syndrome is the result of an extra copy of chromosome 21 in all or some cells.

Translocating the Downs syndrome. Additionally, Downs syndrome can develop before or during conception if a piece of chromosome 21 translocates (attaches to another chromosome). These kids have two copies of chromosome 21 as usual, but they also contain additional chromosome 21 genetic material linked to another chromosome.

#### **5.3 Crouzon Syndrome**

Synonyms include the following:

craniofacial dysostosis,

craniostenosis, Crouzon type,

Crouzon craniofacial dysostosis.

Crouzon syndrome is a rare genetic disorder. It is a form of craniosynostosis, a condition in which there is premature fusion of the fibrous joints (sutures) between certain bones of the skull. Symptoms primarily include abnormalities of the face and head [20].

Signs and symptoms

The primary features of Crouzon syndrome, also known as craniofacial dysostosis, are pronounced facial deformities and premature closure of the fibrous joints (cranial sutures) connecting some of the skull's bones. Malformations of the cranium and face can range from minor to potentially severe, even in members of the same family who are typically unaffected [21]. Crouzon syndrome is inherited autosomally dominantly and is brought on by changes (mutations) in one of the FGFR genes, typically FGFR2.

The bony cavities of the skull that house the eyeballs or the orbits in the majority of people are unusually shallow. The consequence is a protrusion or bulge forward of the eyeballs, known as proptosis [22]. About 30% of those with Crouzon syndrome go on to develop hydrocephalus, a disorder marked by reduced flow.

*Diagnosis of Dentofacial Anomalies DOI: http://dx.doi.org/10.5772/intechopen.107416*

## Diagnosis

Based on a thorough clinical evaluation, the recognition of recognisable physical characteristics and a battery of specialised testing, Crouzon syndrome is typically diagnosed at birth or during infancy. Advanced imaging methods, such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning, may be used during such testing.

Clinical evaluation and testing

MRIs and CT scans are utilised to identify or detect some abnormalities that may be connected to the illness (e.g. craniosynostosis, other skeletal abnormalities). X-rays and a computer are used in CT scanning to produce a film that shows crosssectional images of inside structures. A magnetic field and radio waves are used in MRI to produce finely detailed cross-sectional images of certain organs and tissues.

A Crouzon syndrome diagnosis can be confirmed by molecular genetic testing (**Figures 12** and **13**).
