FRONTONASAL DYSPLASIA

(MEDIAN CLEFT SYNDROME)

Frontonasal dysplasia is a poorly defined syndrome consisting of a range of midline facial defects involving the eyes, forehead and nose.

• Sporadic.
• Autosomal dominant inheritance either as a sporadic mutation or phenocopy (3).

Clinical Features

A. Variability in severity of expression

B. Eyes

1. Hypertelorism

2. Lateral displacement of inner canthi

C. Forehead

1. Widown’s peak

2. Defect in midline frontal bone (cranium bifidum occultum)

D. Nose

1. Varies from notched broad nasal tip, divided nostrils with hypoplasia, absence of prolabium and premaxilla with cleft lip

2. Broad nasal root

3. Lack of formation of nasal tip

E. Occassional abnormalities

1. Accessory nasal tags

2. Anomalies of optic disk, optic nerve, retina, or eye (colobomas, cataracts)

3. Preauricular tags, low-set ears

4. Conductive deafness

5. Mental deficiency (8-20%)

a. Seems to be more severe when extracephalic anomalies occur or when hypertelorism is very severe

b. Probability low if features above are not as sever

6. Frontal cutaneous lipoma or lipoma of corpus callosum

7. Agenesis of corpus collosum

8. Anterior basal encephalocele

9. Tetralogy of Fallot

10. Cleft lip and/or cleft palate

F. Usually requires radical cosmetic surgery to repair

G. Natural history and lifespan depend on severity and complications but usually not significantly different from expected

CLASSIFICATION

• DeMyer (1) classified the syndrome into four different facies based on the presence of true ocular hypertelorism and the degree of median facial malformations.
• Sedano and co-workers (2) subclassified it into four different facies based on embryological considerations and termed the disorder frontonasal dysplasia.

EMBRYOLOGY

Failure of development of the nasal capsule results in the primitive brain vesicle filling the space normally occupied by the capsule (this produces the cranium bifidum occultum). Arrest in development of the eyes and nostrils at this time results in them maintaining their normal position, but produces hypertelorism and midline facial clefting.

ULTRASOUND

Diagnosis is made by a combination of two or more of the following (1,4):

1. Cranium bifidum occultum.
2. Hypertelorism.
3. Median cleft nose.
4. Median cleft lip.
5. Median cleft dysplasia.

DIFFERENTIAL DIAGNOSIS

A. Oculo-auricular-vertebral spectrum

B. Frontofacionasal dysostosis – autosomal recessive inheritance

C. Craniofrontonasal dysplasia

REFERENCES

1. DeMyer W. The median cleft face syndrome: Differential diagnosis of cranium bifidum occultum, hypertelorism, and median cleft nose, lip and palate. Neurology 1967;17:961.
2. Sedano HO, Cohen MM Jr, Jirasek JE Jr et.al. Frontonasal dysplasia. J Pediatr 1970;76:906.
3. Cohen MM Jr, Sedano HO, Gorlin RJ et.al. Frontonasal dysplasia (median cleft face syndrome): Comments on etiology and pathogenesis. Birth Defects, Orig Artic Ser 1971;VII(7):117.
4. Frattarelli JL, Boley TJ, Miller RA. Prenatal diagnosis of frontonasal dysplasia (median cleft syndrome). J Ultrasound Med 1996;15:81-83.