**6.1 Single defect**

A *single defect* (*isolated defect*) affects only one specific part of an organ or a single organ or a local region of the body. Single defects include an eyelid coloboma, a cleft palate, a patent ductus arteriosus and a hypospadias. Most congenital defects are single and their etiology is often multifactorial. A given type of single defect may be viewed as part of certain syndromes, pointing out that different causes can affect the same developmental field, leading to the same result (Aase, 1990). Single defects are monotopic defects, which are the result of a disturbance in a single monotopic primary field or in a secondary field.

### **6.2 Multiple congenital anomalies**

The occurrence of two or more defects in one or more parts of the body of the same individual is characterized as a *multiple congenital anomaly* (Fig. 10-C). However, the concomitant occurrence of anomalies does not define the etiology. A given pattern of defects may indeed have a specific etiology or may be caused by a variety of possible agents that affect the same developmental fields or a same monotopic or polytopic field.

#### **6.2.1 Syndrome**

A syndrome is a *set of defects* that occur simultaneously in the same individual and result from the *same cause*. Therefore, the pattern of defects must be repeated in all affected individuals. Syndromes are defined after several cases have been described, enabling one to determine which defects actually compose the syndrome and which are accidental. Strictly

86 A Bird's-Eye View of Veterinary Medicine

Fig. 9. Examples of abnormalities of the genitourinary system: A) Perineal hypospadias in a dog. Observe the urethral opening (arrow) located in the perineum, near the anus; B)

Dysmorphisms can affect an individual as a *single defect* (Fig. 10-A and B) or a set of defects (*multiple congenital anomalies*). The latter include syndromes, developmental field defects, associations and sequences. All arise from disorders in one of more developmental field.

A *single defect* (*isolated defect*) affects only one specific part of an organ or a single organ or a local region of the body. Single defects include an eyelid coloboma, a cleft palate, a patent ductus arteriosus and a hypospadias. Most congenital defects are single and their etiology is often multifactorial. A given type of single defect may be viewed as part of certain syndromes, pointing out that different causes can affect the same developmental field, leading to the same result (Aase, 1990). Single defects are monotopic defects, which are the

The occurrence of two or more defects in one or more parts of the body of the same individual is characterized as a *multiple congenital anomaly* (Fig. 10-C). However, the concomitant occurrence of anomalies does not define the etiology. A given pattern of defects may indeed have a specific etiology or may be caused by a variety of possible agents that

A syndrome is a *set of defects* that occur simultaneously in the same individual and result from the *same cause*. Therefore, the pattern of defects must be repeated in all affected individuals. Syndromes are defined after several cases have been described, enabling one to determine which defects actually compose the syndrome and which are accidental. Strictly

result of a disturbance in a single monotopic primary field or in a secondary field.

affect the same developmental fields or a same monotopic or polytopic field.

Ambiguous genitalia in a dog with XX true hermaphroditism.

**6. Clinical presentation of dysmorphisms** 

**6.1 Single defect** 

**6.2.1 Syndrome** 

**6.2 Multiple congenital anomalies** 

speaking, however, the cause is not always known, but it is presumed. Generally, syndromes are considered as having resulted from a disorder in more than one developmental field (Spranger, 1982). Examples: 1) Hurler Syndrome (mucopolysaccharidosis I), a recessive autosomal syndrome in which there is a deficiency of alpha-L-iduronidase. Affected dogs have corneal opacity, facial dysmorphism, joint abnormalities, aortic dilation and thickened heart valves (Traas et al., 2007); 2) Hunter Syndrome (mucopolysaccharidosis II), an X-linked recessive syndrome in which there is iduronate-sulfatase deficiency. Affected dogs have a course facial appearance, macrodactyly, corneal dystrophy and neurological alterations (Wilkerson, 1998).

Fig. 10. Examples of single defect: A) Dog with cleft palate; B) Eyelid coloboma (arrow) in a cat; C) Example of a multiple congenital anomaly in a dog (meningocele and peromelia).

#### **6.2.2 Developmental field defects**

Developmental field defects are resulting from a *dysmorphogenetic response* of a developmental field (Hersch et al., 2002) and are causally heterogeneous. This means that the *same field reacts in a similar way to different factors*. They may be multiple anomalies that affect an area of anatomically related structures, being monotopic field defects; or they may be anomalies in different areas of the body, being polytopic field defects. Holoprosencephaly in its different degrees is a monotopic field, such as semilobar holoprosencephaly in Morgan horses (Kock et al., 2005), and may be associated with otocephaly, as reported by Martínez et al., (2006) in a Rottweiler dog. Lumbosacral agenesis in its different degrees is a polytopic field defect and has been described in a number of domestic species, such as sheep (Denis, 1975), cattle (Jones, 1999; Son et al., 2008), pigs (Avedillo & Camón, 2007) and dogs (Araújo et al., 2008).

#### **6.2.3 Association**

Association is a *combination of two or more defects* in the same individual and occurs in the population more frequently than could be expected merely at random, but it does *not have a specific cause*. Like syndromes, associations must be defects involving more than one developmental field (or only one polytopic field), but are etiologically heterogeneous.

congenital defects too must be considered a possible cause of clinical conditions identified in the first months of life. Although most of these defects are identified in the first six months, there are cases that manifest clinically later on and are diagnosed in adult life. For example, many cases of dogs with pulmonic stenosis show no clinical signs for years

Fig. 11. A) Holoprosencephaly in a pig; B and C) Clinical signs of cerebellar disorder in a lamb (backward contraction of the neck, thoracic limbs in hyperextension and flexed pelvic

**7. Medical history, physical examination and management of dysmorphic** 

In dysmorphology, the clinical activities that lead to the diagnosis (medical history, physical examination, complementary examinations, etc.) and the therapeutic procedures are that same as those of clinical medicine and/or surgery, with the inherent aspects of each specialty and any adaptations that each dysmorphic condition may require. In any situations, a correct diagnosis is very important for making the best decision. It has implications in terms of prognosis and possible treatment. All procedures should be noted according to well defined criteria in order to obtain a complete and consistent record, whose importance in terms of diagnosis and therapy transcends each case, enabling comparisons with new cases and generating innovations. The following topics introduce some general

A detailed and solid medical history is one of the pillars of the diagnosis. It should include information about the environment in which the mother lives or lived, maternal diseases

limbs) as a result of cerebellar hypoplasia.

observations concerning these aspects.

**7.1 Medical history** 

(Ware, 2011).

**patients** 

Example: VACTERL (or VATER) is an acronym for the non-random co-occurrence of vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) and limb defects (L). The presence of two of these anomalies in the same patient is considered sufficient for diagnosis (Källén et al., 2001), although other researchers are of the opinion that at least three are required (Martínez-Frías, 1994; Faivre et al., 2005). The defects that compose VACTERL association originate during blastogenesis and the existence of a characteristic pattern of abnormalities caused by different factors suggests a dysmorphogenetic response from a primary developmental field (Hersch et al., 2002). For this reason, Martínez-Frías & Frías (1999) consider it a primary, polytopic developmental field defects. In animals, the first record of a spontaneous occurrence of VACTERL association was made by Moura et al. (2010) in a female cat with costovertebral defects, anal atresia, heart and kidney defects, bilateral radial agenesis and persistent cloaca, but no tracheoesophageal fistula.

#### **6.2.4 Sequence**

This is a set of defects in an individual and results from an *initial defect* (malformation, disruption, dysplasia or deformation) that interferes in the development process, *leading to additional defects*. For example, as the result of a persistent right aortic arch, a ring is formed around the thoracic esophagus, causing an increased diameter of the esophagus in the cervical segment (a pouch is formed cranially to the point of constriction). A bilateral elbow dysplasia can cause a luxation of the elbows, which leads to medial rotation of the forearms, deforming the carpus. Micrognatia causes retroglossoptosis, which in turn can cause a cleft palate and respiratory distress (Pierre Robin sequence).

#### **6.3 Further considerations**

The same dysmorphism can appear in isolation or be part of syndromes or associations. Single defects or multiple defects of the same area (monotopic defects) without anomalies in other areas of the body are often called *nonsyndromic defects* to distinguish them from the same defects in an individual affected by a syndrome. A given defect can be a manifestation of the same anomaly expressed in different degrees, as is common in the developmental field defects. Any degree of expression of these cases is part of the total spectrum of a multiple anomaly. For instance, a single upper central incisor or an iris coloboma may be a minimum clinical sign of the total spectrum of holopresencephaly (Fig. 11-A), which at the most serious degree includes anomalies such as cyclopia, proboscis, absence of optic nerves and cleft lip and palate (Spranger, 1982; Jones, 2006). Dysmorphisms that affect the right and left side of the body (*symmetrical dysmorphisms*) are more likely to have a genetic cause than those that affect only one side (*asymmetric dysmorphisms*). However, this is not a rule (Turnpenny & Ellard, 2007). When a dysmorphism is extenal it is easily observed, especially if it is a major dysmorphism. Internal dysmorphisms, in turn, can only be confirmed by imaging tests, endoscopic viewing or a postmortem examination. Nevertheless, affected individuals will show clinical signs (Fig.11-B and C) at some time during their development, enabling a diagnosis using the aforementioned examinations. Internal congenital defects must be on the list of possible diagnoses in stillborn and critically ill newborn animals, although they may look normal externally. Internal

Example: VACTERL (or VATER) is an acronym for the non-random co-occurrence of vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) and limb defects (L). The presence of two of these anomalies in the same patient is considered sufficient for diagnosis (Källén et al., 2001), although other researchers are of the opinion that at least three are required (Martínez-Frías, 1994; Faivre et al., 2005). The defects that compose VACTERL association originate during blastogenesis and the existence of a characteristic pattern of abnormalities caused by different factors suggests a dysmorphogenetic response from a primary developmental field (Hersch et al., 2002). For this reason, Martínez-Frías & Frías (1999) consider it a primary, polytopic developmental field defects. In animals, the first record of a spontaneous occurrence of VACTERL association was made by Moura et al. (2010) in a female cat with costovertebral defects, anal atresia, heart and kidney defects, bilateral radial agenesis and persistent cloaca,

This is a set of defects in an individual and results from an *initial defect* (malformation, disruption, dysplasia or deformation) that interferes in the development process, *leading to additional defects*. For example, as the result of a persistent right aortic arch, a ring is formed around the thoracic esophagus, causing an increased diameter of the esophagus in the cervical segment (a pouch is formed cranially to the point of constriction). A bilateral elbow dysplasia can cause a luxation of the elbows, which leads to medial rotation of the forearms, deforming the carpus. Micrognatia causes retroglossoptosis, which in turn can cause a cleft

The same dysmorphism can appear in isolation or be part of syndromes or associations. Single defects or multiple defects of the same area (monotopic defects) without anomalies in other areas of the body are often called *nonsyndromic defects* to distinguish them from the same defects in an individual affected by a syndrome. A given defect can be a manifestation of the same anomaly expressed in different degrees, as is common in the developmental field defects. Any degree of expression of these cases is part of the total spectrum of a multiple anomaly. For instance, a single upper central incisor or an iris coloboma may be a minimum clinical sign of the total spectrum of holopresencephaly (Fig. 11-A), which at the most serious degree includes anomalies such as cyclopia, proboscis, absence of optic nerves and cleft lip and palate (Spranger, 1982; Jones, 2006). Dysmorphisms that affect the right and left side of the body (*symmetrical dysmorphisms*) are more likely to have a genetic cause than those that affect only one side (*asymmetric dysmorphisms*). However, this is not a rule (Turnpenny & Ellard, 2007). When a dysmorphism is extenal it is easily observed, especially if it is a major dysmorphism. Internal dysmorphisms, in turn, can only be confirmed by imaging tests, endoscopic viewing or a postmortem examination. Nevertheless, affected individuals will show clinical signs (Fig.11-B and C) at some time during their development, enabling a diagnosis using the aforementioned examinations. Internal congenital defects must be on the list of possible diagnoses in stillborn and critically ill newborn animals, although they may look normal externally. Internal

but no tracheoesophageal fistula.

**6.3 Further considerations** 

palate and respiratory distress (Pierre Robin sequence).

**6.2.4 Sequence** 

congenital defects too must be considered a possible cause of clinical conditions identified in the first months of life. Although most of these defects are identified in the first six months, there are cases that manifest clinically later on and are diagnosed in adult life. For example, many cases of dogs with pulmonic stenosis show no clinical signs for years (Ware, 2011).

Fig. 11. A) Holoprosencephaly in a pig; B and C) Clinical signs of cerebellar disorder in a lamb (backward contraction of the neck, thoracic limbs in hyperextension and flexed pelvic limbs) as a result of cerebellar hypoplasia.
