**Non Aneuploidic syndromic**


Micrognathia can result in a malocclusion (poor bite), where the teeth and jaws do not line up properly, or in more severe cases, in difficulties in breathing or swallowing. Underdeveloped mandibles can also cause severe psychological and functional impact in the growing of the child, and may be associated with life-threatening complications such as obstructive sleep apnea [12].

*4.2.2. Inner epicanthal fold*

**Figure 3.** Brushfield spot.

elevation of the nasal bridge [16].

Lemli-Opitz syndrome.

**Figure 4.** Inner epicanthal fold.

conditions such as blepharophimosis, palpebral ptosis.

Epicanthal fold represents the oblique or vertical skin fold [14], which starts from the upper eyelid to the lower eyelid, covering the inner corner of the eye and it is most frequently bilateral (**Figure 4**). This feature is also named plica palpebronasalis or the historically Mongolian fold. These skin folds appear through the excessive development of the skin across the nasal bridge. This excess skin presents a certain tension determined by the ectopic orbicularis oculi muscle fibers and connective tissue [15], leading to residual horizontal skin over the nasal bridge.

The Neonate with Minor Dysmorphisms http://dx.doi.org/10.5772/intechopen.71902 511

One of the main facial features that is often closely associated with the epicanthic fold is the

Factors influencing this facial trait are: geographical ancestry, age and certain pathological

The epicanthic fold may be an isolated congenital anomaly, or it may be a manifestation of other syndromes [17, 18]. Approximately 60% of people with Down syndrome have this fold, named "the Mongoloid fold" by John Langdon Down. In Zellweger's syndrome, epicanthic folds are present and prominent [19]. Other pathological conditions that highlight this epicanthic fold are the fetal alcohol syndrome, phenylketonuria, Turner syndrome and Smith-

#### **4.2. Minor eye anomalies**

Although there is a wide variety of ocular morphology (in terms of gender, ethnicity and age), a careful analysis of some dysmorphological entities and objective measurements during the clinical examination can help diagnose some features outside of the normal standards, which may help identifying a syndrome.

#### *4.2.1. Brushfield spots*

Brushfield spots are white, yellow-colored spots on the anterior surface of the iris or small white-gray areas around the pupil.

Brushfield spots are observed in 20% of normal neonates, regardless of the color of their eyes. 85% of people with blue eyes show these spots (**Figure 3**).

They are also very common (80%) in the iris of children with trisomy 21. In children with Down syndrome and brown eyes, these spots are visible in 15–17% of cases only, being masked by normal pigmented cells. In cases with black eyes, they cannot be identified.

Brushfield spots should be differentiated from normal stromal condensation called "Kunkmann Wolffian bodies", which are light-colored, located peripherally in the iris and are not considered to be ocular dysmorphisms.

**Figure 3.** Brushfield spot.

**Non Aneuploidic syndromic**

• Hydrolethalus syndrome

• Pena Shokeir syndrome • Pierre Robin sequence

• Smith Lemli Opitz syndrome

• Goldenhar syndrome (hemifacial microsomia)

• Treacher Collins syndrome (mandibulofacial dysostosis)

85% of people with blue eyes show these spots (**Figure 3**).

Micrognathia can result in a malocclusion (poor bite), where the teeth and jaws do not line up properly, or in more severe cases, in difficulties in breathing or swallowing. Underdeveloped mandibles can also cause severe psychological and functional impact in the growing of the child, and may be associated with life-threatening complications such as obstructive sleep apnea [12].

Although there is a wide variety of ocular morphology (in terms of gender, ethnicity and age), a careful analysis of some dysmorphological entities and objective measurements during the clinical examination can help diagnose some features outside of the normal standards, which

Brushfield spots are white, yellow-colored spots on the anterior surface of the iris or small

Brushfield spots are observed in 20% of normal neonates, regardless of the color of their eyes.

They are also very common (80%) in the iris of children with trisomy 21. In children with Down syndrome and brown eyes, these spots are visible in 15–17% of cases only, being masked by normal pigmented cells. In cases with black eyes, they cannot be identified.

Brushfield spots should be differentiated from normal stromal condensation called "Kunkmann Wolffian bodies", which are light-colored, located peripherally in the iris and are not

• Lethal multiple pterygium syndrome

510 Congenital Anomalies - From the Embryo to the Neonate

• Fryns syndrome

• Nager syndrome

• Seckel syndrome

• Stickler syndrome

**4.2. Minor eye anomalies**

*4.2.1. Brushfield spots*

may help identifying a syndrome.

white-gray areas around the pupil.

considered to be ocular dysmorphisms.

• TAR syndrome

### *4.2.2. Inner epicanthal fold*

Epicanthal fold represents the oblique or vertical skin fold [14], which starts from the upper eyelid to the lower eyelid, covering the inner corner of the eye and it is most frequently bilateral (**Figure 4**). This feature is also named plica palpebronasalis or the historically Mongolian fold.

These skin folds appear through the excessive development of the skin across the nasal bridge. This excess skin presents a certain tension determined by the ectopic orbicularis oculi muscle fibers and connective tissue [15], leading to residual horizontal skin over the nasal bridge.

One of the main facial features that is often closely associated with the epicanthic fold is the elevation of the nasal bridge [16].

Factors influencing this facial trait are: geographical ancestry, age and certain pathological conditions such as blepharophimosis, palpebral ptosis.

The epicanthic fold may be an isolated congenital anomaly, or it may be a manifestation of other syndromes [17, 18]. Approximately 60% of people with Down syndrome have this fold, named "the Mongoloid fold" by John Langdon Down. In Zellweger's syndrome, epicanthic folds are present and prominent [19]. Other pathological conditions that highlight this epicanthic fold are the fetal alcohol syndrome, phenylketonuria, Turner syndrome and Smith-Lemli-Opitz syndrome.

**Figure 4.** Inner epicanthal fold.

Four types of epicanthic folds [20] have been identified:

**1.** Epicanthus tarsalis: the fold is most prominent along the upper eyelid - the normal anatomical variant of the Asian eyelid

• Basal cell nevus syndrome

• Wolf-Hirschhorn syndrome • Andersen-Tawil syndrome

• Waardenburg syndrome

Since hypertelorism is a facial dysmorphism associated with a large and diverse number of congenital disorders and syndromes, the mechanism of hypertelorism is heterogeneous.

The Neonate with Minor Dysmorphisms http://dx.doi.org/10.5772/intechopen.71902 513

A number of theories have attempted to pinpoint this anomaly, such as: the early ossification of the lower wings of the sphenoid, the increasing width of the ethmoid sinuses, the formation and abnormal development of the skull, which can be seen in syndromes such as Apert

In the normal eye, the eyelids are generally positioned so that the lateral canthus is about 1 mm higher than the medial canthus. The palpebral slant is the direction of the slant of a line

The upper or lower slant of the palpebral fissure can be a genetic or ethnic feature (Asian population), but there are a number of conditions and syndromes manifested through this anomaly, isolated or in association with others, such as the Treacher Collins syndrome, Franceschetti (oculo-mandibulo-facial) syndrome, Down syndrome, fetal alcohol syndrome

The identification of an abnormal slant of the palpebral fissure requires a thorough medical examination with an analysis of family history, a physical exam to detect other associated disorders/abnormalities and paraclinical investigations (karyotype), enzyme assays and

The incidence of ear malformations is approximately 1 in 3800 newborns [24] and accounts for 50% of all ENT (Ear, Nose, and Throat) malformations. The most common malformations are

• Cri du chat syndrome

and Crouzon [22].

*4.2.4. Slanting of palpebral fissures*

or other genetic disorders.

metabolic studies [23].

**4.3. Minor ear anomalies**

that goes from the outer corner of the eye to the inner corner.

unilateral and localized in the outer and middle ear.

• DiGeorge syndrome

• Apert syndrome

• Neurofibromatosis • Leopard syndrome • Crouzon syndrome

• Loeys-Dietz syndrome


The evolution of epicanthic folds is favorable: a mild degree of epicanthus disappears most frequently with further development of the nose and massive facial bone [20, 21].

Surgical correction is only occasionally required. One of the surgical indications is in the case of epicanthus inversus, which does not resolve on its own with further growth and development of the face [15].

#### *4.2.3. Telecanthus and hypertelorism*

Telecanthus is the increased distance between the medial canthi of both eyes, with normal interpupillary distance. This condition is different to hypertelorism, which refers to an increased distance between the orbits [22].

Telecanthus may appear secondary to obstetrical traumas such as naso-orbito-ethmoidal fractures, and it may be an ethnic marker. It could also represent the expression of sinus or orbital tumors, or it may be associated with syndromes such as:


Hypertelorism is a clinical sign in a wide range of affections and syndromes such as:


Four types of epicanthic folds [20] have been identified:

**3.** Epicanthus palpebralis: involves both upper and lower eyelids

tomical variant of the Asian eyelid

512 Congenital Anomalies - From the Embryo to the Neonate

blepharophimosis syndrome

*4.2.3. Telecanthus and hypertelorism*

distance between the orbits [22].

• Sinus polyps – Kartagener syndrome

tumors, or it may be associated with syndromes such as:

sac

of the face [15].

• Down syndrome • Turner syndrome

• Klinefelter syndrome • Fetal alcohol syndrome • Cri du chat syndrome • Dubowitz syndrome • Noonan syndrome • SHORT syndrome

• Edwards syndrome

• 1q21.1 duplication syndrome

**1.** Epicanthus tarsalis: the fold is most prominent along the upper eyelid - the normal ana-

**2.** Epicanthus inversus: the fold is most prominent along lower eyelid - associated with

**4.** Epicanthus superciliaris: the fold originates from the brow and follows down to the lacrimal

The evolution of epicanthic folds is favorable: a mild degree of epicanthus disappears most

Surgical correction is only occasionally required. One of the surgical indications is in the case of epicanthus inversus, which does not resolve on its own with further growth and development

Telecanthus is the increased distance between the medial canthi of both eyes, with normal interpupillary distance. This condition is different to hypertelorism, which refers to an increased

Telecanthus may appear secondary to obstetrical traumas such as naso-orbito-ethmoidal fractures, and it may be an ethnic marker. It could also represent the expression of sinus or orbital

Hypertelorism is a clinical sign in a wide range of affections and syndromes such as:

frequently with further development of the nose and massive facial bone [20, 21].


Since hypertelorism is a facial dysmorphism associated with a large and diverse number of congenital disorders and syndromes, the mechanism of hypertelorism is heterogeneous.

A number of theories have attempted to pinpoint this anomaly, such as: the early ossification of the lower wings of the sphenoid, the increasing width of the ethmoid sinuses, the formation and abnormal development of the skull, which can be seen in syndromes such as Apert and Crouzon [22].

#### *4.2.4. Slanting of palpebral fissures*

In the normal eye, the eyelids are generally positioned so that the lateral canthus is about 1 mm higher than the medial canthus. The palpebral slant is the direction of the slant of a line that goes from the outer corner of the eye to the inner corner.

The upper or lower slant of the palpebral fissure can be a genetic or ethnic feature (Asian population), but there are a number of conditions and syndromes manifested through this anomaly, isolated or in association with others, such as the Treacher Collins syndrome, Franceschetti (oculo-mandibulo-facial) syndrome, Down syndrome, fetal alcohol syndrome or other genetic disorders.

The identification of an abnormal slant of the palpebral fissure requires a thorough medical examination with an analysis of family history, a physical exam to detect other associated disorders/abnormalities and paraclinical investigations (karyotype), enzyme assays and metabolic studies [23].

#### **4.3. Minor ear anomalies**

The incidence of ear malformations is approximately 1 in 3800 newborns [24] and accounts for 50% of all ENT (Ear, Nose, and Throat) malformations. The most common malformations are unilateral and localized in the outer and middle ear.

Auricular malformations in newborns may be genetic (associated with syndromes or not, with family history, spontaneous mutations) or intrauterine (acquired by deformation mechanisms).

External ear malformations may involve the orientation, position, size, and external configuration of the pinna. The absence of the external ear can be identified (anotia).
