**5.4 Foetal alcohol syndrome**

This is the most severe foetal alcohol spectrum disorder. These are a group of birth defects that can happen when a pregnant woman drinks alcohol (**Figure 14**). Other foetal alcohol syndrome disorders (FASDs) include the following [22, 23]:

partial foetal alcohol syndrome,

alcohol-related birth defects,

alcohol-related neurodevelopment disorder,

neurobehavioural disorder associated with prenatal alcohol exposure.

They can include the following:

**Figure 12.** *Salient features of Crouzon syndrome and panoramic image to show bone density and affected teeth.*

#### **Figure 13.**

*Skull radiograph A, anterior-posterior and B, lateral views showing prominent convolutional markings appearing as a copper beaten skull. Courtesy: JSS Medical College, Mysore.*

#### **Figure 14.**

*Salient featues of foetal alcohol syndrome.*

problems with the heart, kidney and bones, learning disabilities and low IQ, trouble with memory, coordination and attention, hyperactivity. Problems with sleep and suckling as an infant. Foetal alcohol syndrome can have many symptoms, including the following: Physical defects: small head and brain size, vision or hearing problems, joint, limb and finger deformities, distinctive facial features such as small eyes, thin upper lip and a ridge between the nose and upper lip. Neurological problems: learning problems, coordination and balance problems, trouble reasoning, hyperactivity, moodiness. Behavioural issues: poor social skills, difficulty in school, poor impulse control.

## **5.5 Goldenhar syndrome (GS)**

Oculoauriculovertebral dysplasia, also referred to as hemifacial microsomia, manifests clinically in a variety of ways, including abnormalities of the craniofacial, vertebral, cardiac, renal, and central nervous systems1. Epibulbar dermoids, microtia, mandibular hypoplasia, and spinal abnormalities are among the symptoms of GS that are frequently present. Hemifacial microsomia, the term used to characterise the typical facial feature of GS patients, as well as the other anomalies associated with this disease, are most likely the result of first and second brachial

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

arch development problems. These developmental abnormalities appear to have a variety of causes [24, 25].

However, the absence of evident features or the unknowledge of GS characteristics makes the diagnosis difficult and late. The classical features of GS patients involve ocular anomalies, including microphthalmia, anophthalmia, epibulbar dermoid (or lipodermoid) tumours, and eyelid colobomas, aural defects, such as preauricular tags, anotia, microtia and hearing loss, vertebral abnormalities, such as scoliosis, hemivertebrae and cervical fusion, and mandibular hypoplasia 8–12. Facial involvement is usually unilateral, resulting in a marked asymmetry. In the series presented here, the patients were affected unilaterally, and all showed mandibular hypoplasia and vertebral anomaly [26].

Syndromes derived from aberrations in the development of the first and second branchial arches are in the spectrum of GS, including Treacher-Collins syndrome (TCS). The presence of facial asymmetry and far less hypoplasia of the malar bones in GS are the important features to differentiate it from TCS. The TCS-affected patients presented downward slating palpebral fissures, colobomas, zygomatic and mandibular hypoplasia, partial absence of the lower eyelid cilia, and abnormalities of the ears (**Figure 15**).

#### **5.6 Van der Woude syndrome**

The disease has an impact on how the face develops. A cleft lip, a cleft palate (an opening in the roof of the mouth) or both are common birth defects in those who have this condition. Affected people frequently have depressions (pits) close to the centre of the lower lip, which may appear moist since salivary and mucous glands are

#### **Figure 15.**

*Skeletal and facial phenotypes of patient #2 of this study. (A) Anterior standing photograph of the patient, demonstrating severe lordoscoliosis. (B) Frontal view of the face showing marked facial asymmetry, malocclusion and eye involvement characterised by microphthalmia and eyelid coloboma of the left eye. (C) Lateral view of the face showing ear malformations, including microtia and preauricular tags (the parents signed informed consent authorising the publication of these pictures).*

located there. Also possible are little tissue lumps on the lower lip. Van der Woude syndrome patients can have tooth loss [27].

Like other people with these facial disorders, those who have cleft lip and/or palate also have a greater risk of delayed language development, learning impairments or other modest cognitive issues [28]. The average IQ of individuals with van der Woude syndrome is not significantly different from that of the general population.

#### **5.7 van der Woude syndrome (VWS)**

Lip pits\* in combination with wiIRF6-related illnesses often fall on a spectrum, ranging from popliteal pterygium syndrome (PPS) at the more severe end to isolated cleft lip and palate and Van der Woude syndrome (VWS) at the moderate end. Rarely, IRF6 pathogenic mutations have also been identified in people with spina bifida (2/192) and nonsyndromic orofacial clefts (18/3811; 0.47 percent). People who have VWS exhibit one or more of the oddities listed below: congenital paramedian lower-lip fistulae (pits), which are typically bilateral, or occasionally tiny mounds with a sinus tract emerging from a mucous gland of the lip, uneven lip (CL) and missing palate (CP). It should be noted that cleft lip with or without cleft palate (CLP) is seen almost twice as frequently as CP alone. Submucous palate cleft (SMCP) has one of the following:

cleft lip with or without cleft palate (CL ± P)

cleft palate (CP)

submucous cleft palate (SMCP)

lip pits\* alone and a first-degree relative with CL ± P, CP, or SMCP

CL ± P, CP or SMCP and a first-degree relative with lip pits\*

CL or CL + P and CP in the same family

\* Lip pits are most often paramedian on the lower lip and can include mounds with a sinus tract leading from a mucous gland of the lip.

## **5.8 Popliteal pterygium syndrome (PPS)**

This syndrome includes the following condition: popliteal pterygia, syndactyly, abnormal external genitalia, ankyloblepharon, pyramidal skin on the hallux, a spectrum of intraoral adhesions, the most severe of which is complete syngnathia.

Musculoskeletal anomalies are rarely reported (e.g. talipes equinovarus, digital reduction, spina bifida occulta, bifid ribs, short sternum).

IRF6-related neural tube defect. Two individuals with an IRF6 pathogenic variant and spina bifida have been reported. Neural tube defects due to an IRF6 pathogenic variant cannot be clinically distinguished from the neural tube defects of other aetiologies. Orofacial cleft was brought on by IRF6. There have been reports of 18 people who had either an orofacial cleft or an IRF6 pathogenic mutation. Clinically, orofacial clefts caused by IRF6 pathogenic variants cannot be discriminated from those caused by other causes.

A proband is diagnosed with an IRF6-related illness based on suggestive evidence, and molecular genetic testing identifies a heterozygous pathogenic mutation in IRF6 [28].

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

A word is frequently used in clinical genetics to refer to the various methods utilised to pinpoint the molecular causes of genetic illness. Examples of molecular genetic tests include genotyping to identify particular pathogenic variants, gene sequencing to identify pathogenic variations, and amplification or hybridisation techniques to identify copy number variants affecting one or more genes (e.g. qPCR, array CGH, MLPA). Epigenetic alterations are detected using methylation-specific methods.

#### **5.9 Apert syndrome**

A hereditary condition known as Apert syndrome is characterised by skeletal deformities. The premature closing of the skull's bones is a major aspect of Apert syndrome (craniosynostosis). Early fusion alters the contour of the head and face and stops the skull from developing normally. The number of fingers and toes that are fused together (syndactyly) varies as well [20].

Many of the distinctive facial characteristics of Apert syndrome are caused by craniosynostosis. Midface hypoplasia, a beaked nose, a wrinkled forehead and a hole in the roof of the mouth are all results of premature skull bone fusion, which prevents the head from growing normally (a cleft palate). Dental problems can result from an underdeveloped upper jaw in people with Apert syndrome.

Many people with Apert syndrome experience vision issues as a result of eye abnormalities, which can include bulging eyes (exophthalmos), wide-set eyes (hypertelorism), outward-facing eyes (downslanting palpebral fissures), eyes that do not look in the same direction (strabismus) and shallow eye sockets (ocular proptosis). Apert syndrome patients with deformed ear structures may experience hearing loss or recurrent ear infections.

People with Apert syndrome who have abnormal facial and cranial structure may also experience breathing issues due to partial airway obstruction. The brain's development is also impacted by craniosynostosis, which may impair intellectual growth. Cognitive abilities range from normal to mild-to-moderate intellectual disability in those with Apert syndrome [29].

Apert syndrome patients exhibit syndactyly of the fingers and toes. Although the severity of the fusion varies, the hands are typically worse off than the feet. Three fingers on each hand and foot are most frequently fused together. The fingers and toes are merged in the most extreme cases. Apert syndrome patients very rarely have extra fingers or toes (polydactyly). Some Apert syndrome sufferers have anomalies in their shoulder or elbow bones. These bone issues might make it difficult to walk around and interfere with daily tasks. While some persons only experience anomalies on one side of the body, others experience abnormalities on both sides.

Hyperhidrosis, oily skin and additional signs and symptoms of Apert syndrome can be present (**Figure 16**).

#### **5.10 Orofacial digital syndrome**

The oral-facial-digital syndrome has been linked to the OFD1 gene. Oral-facialdigital syndrome type I is caused by mutations in this gene. Affected family members with a type VII condition were also found to have mutations in the OFD1 gene; nevertheless, experts currently think that type VII and type I disorders are identical [30].

The development of the oral cavity (the mouth and teeth), facial features and digits are all impacted by the oral-facial-digital syndrome, a collection of connected diseases (fingers and toes).

**Figure 16.** *Salient features of Apert syndrome.*

There are at least 13 different possible types of oral-facial-digital syndrome, according to researchers. By their patterns of symptoms and indications, the various categories are categorised. However, there are a lot of overlaps in the characteristics of the different categories, and some types are not clearly defined. The signs and symptoms of oralfacial-digital syndrome vary widely. However, most forms of this disorder involve problems with the development of the oral cavity, facial features and digits [31]. Most forms are also associated with brain abnormalities and some degree of intellectual disability.

A split (cleft) in the tongue, a tongue with an odd-lobed form and the development of noncancerous tumours or nodules on the tongue are among the abnormalities of the oral cavity that occurs in many types of oral-facial-digital syndrome. Additionally, those who are affected might have additional, missing or broken teeth. An aperture in the roof of the mouth is another typical characteristic (a cleft palate). The lip may be abnormally attached to the gums in certain persons with oral-facial-digital syndrome due to bands of excess tissue known as hyperplastic frenula.

Cleft lips, large noses with flat nasal bridges and widely separated eyes are distinctive facial characteristics that are frequently linked to oral-facial-digital syndrome (hypertelorism).

Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly) or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome [31].

Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterised by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the

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

blood. Other forms of oral-facial-digital syndrome are characterised by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss and heart defects.

#### **5.11 Treacher Collins syndrome**

SYNONYMUS.

Franceschetti-Zwalen-Klein syndrome.

mandibulofacial dysostosis.

Treacher Collins-Franceschetti syndrome.

Treacher Collins syndrome (TCS), a rare genetic condition, is distinguished by recognisable deformities of the head and face. The zygomatic complex, cheekbones, jaws, palate and mouth are typically underdeveloped in cranial anomalies, which can cause breathing and feeding issues [32]

TCS is mainly brought on by modifications (mutations) in the TCOF1 gene, but it is also linked to changes in the POLR1B, POLR1C or POLR1D genes. While autosomal dominant inheritance is the situation for TCOF1 and POLR1B, autosomal recessive inheritance is the case for POLR1C. On the other hand, POLR1D mutations that are both autosomal dominant and recessive have been linked to TCS. The major characteristic features of TCS encompass certain bones of the face, ears and soft tissues around the eyes. Affected individuals present with distinctive facial features and potentially develop hearing and vision problems. The abnormalities of TCS are typically symmetric (almost identical on both sides of the face) and are present at birth (congenital). Speech and language development can be compromised by hearing loss, cleft palate or jaw and airway problems.

**Figure 17.** *Salient features of Treacher Collins syndrome.*

In children with TCS, the cheekbones are hypoplastic or missing, giving the area of the face a sunken or flat appearance. Due to inadequate development of the lower jaw's (mandible) bone (mandibular hypoplasia), the chin and lower jaw appear abnormally tiny (micrognathia). Obstructive sleep apnoea, which is characterised by frequent, brief pauses in breathing and air movement while sleeping, can affect children. Additionally, dental anomalies such as undeveloped (hypoplastic) or misplaced teeth may result from mouth and jaw deformities (malocclusion). There have also been reports of other dental anomalies, such as tooth agenesis (the absence of teeth), enamel opacity (the clouding or darkening of teeth's enamel) and inappropriate (ectopic) eruption of some upper teeth (maxillary molars) (**Figure 17**) [32, 33].
