Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism (an increased distance between the eyes), a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele (an opening of the skull with protrusion of the brain) or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND. Classification
There are multiple classification systems for FND. None of these classification systems have unraveled any genetic factors as the cause of FND. Yet, all of them are very valuable in determining the prognosis of an individual. In the subheadings below, the most common classifications will be explained. Sedano classification
This is a classification based on the embryological cause of FND. De Myer
This classification is based on the morphologic characteristics of FND, that describes a variety of phenotypesBoth of these classifications are further described in table 1. This table originates from the article ‘Acromelic frontonasal dysplasia: further delineation of a subtype with brain malformations and polydactyly (Toriello syndrome), Verloes et al. Signs and symptoms
Midfacial malformations can be subdivided into two different groups. One group with hypertelorism, this includes FND.
Others: polydactyly (an excess of fingers or toes), syndactyly (fused fingers or toes), brachydactyly (short fingers and/or toes), clinodactyly (bending of the fifth fingers towards the fourth fingers), preauricular skin tags, an absent tragus, low set ears, deafness, small frontal sinuses, mental retardation, encephalocele (protrusion of the brain), spina bifida (split spine), meningoencephalocele (protrusion of both meninges), umbilical hernia, cryptorchidism (absence of one or two testes) and possibly cardiac anomalies.The clefts of the face that are present in FND are vertical clefts. These can differ in severity. When they are less severe, they often present with hypertelorism and normal brain development. Mental retardation is more likely when the hypertelorism is more severe or when extracephalic anomalies occur. Cause
Embryogenesis
Midline facial clefts are one of the symptoms in FND. These defects develop in the early stages of embryological development. This is around the 19th to 21st day of pregnancy. The cause of the defect is failure of the mesodermal migration. The mesoderm is one of the germ layers (a collection of cells that have the same embryological origin). As a result of this failure, a midline facial cleft is formed.Another symptom of FND is the V-shaped hairline. In the normal situation, hair growth surrounding the eyes is inhibited. However, in FND this suppression is prevented in the midline by the increased inter-ocular distance. This causes the so-called widow’s peak (a V-shaped hairline) in FND patients.Very early in embryogenesis, the face and neck develop. This development continues until adolescence.