Infants with frontofacionasal dysplasia typically have distinctive malformations of certain bones forming the skull as well as additional facial, nasal, and eye (ocular) defects. For example, the disorder may be associated with premature closure of the fibrous joints (sutures) between particular bones of the skull (craniosynostosis), causing the head to appear unusually short and broad (brachycephaly). In addition, there may be early conversion of fibrous tissue into bone (early ossification) within the base of the skull (sphenoid bone), and some of the air-filled cavities (i.e., paranasal ethmoidal sinuses) within certain bones around the nose may be abnormally large. Underdevelopment of the middle portion of the face (midface hypoplasia) also occurs.
Affected infants may also have additional, associated skull defects, such as underdevelopment (hypoplasia) of part of the bone forming the front of the skull (frontal bone) and an abnormal opening (congenital cleft) within the frontal bone (cranium bifidum). In some infants with a congenital cleft of the skull, there may be protrusion of a portion of the brain and its surrounding membranes (meninges) through the skull defect (encephalocele). However, in others, there may be no associated abnormality of the brain or meninges (cranium bifidum occultum). Frontofacionasal dysplasia is also typically characterized by distinctive nasal abnormalities, such as underdevelopment of the nose and malformation of the nostrils such as underdevelopment of the nasal wings (nasal alae). In addition, affected infants may have incomplete closure of the roof of the mouth (cleft palate) and an abnormal groove in the upper lip (cleft lip). Infants with cleft lip and cleft palate often experience feeding difficulties due to poor suckling ability and increased air swallowing. They also tend to develop dental abnormalities, including improper positioning, malformation, or absence of certain teeth. Some children with these malformations may also experience associated Speech difficulties and have an increased susceptibility to middle ear infections. The fleshy mass (uvula) that hangs in the back of the throat may be split (bifid uvula).
Infants with frontofacionasal dysplasia also have various abnormalities involving the eyes. These may include Widely spaced eyes (ocular hypertelorism); an abnormally increased horizontal distance between the inner angles of the eyelids (telecanthus); and unusually narrow, “S-shaped” eyelid folds (palpebral fissures). In addition, affected individuals may have partial absence of tissue (coloboma) from the colored regions of the eyes (irides) or the upper eyelids; an inability to completely close the eyes (lagophthalmos); drooping of the upper eyelids (ptosis); and absence of eyelashes. In some cases, additional ocular defects may also be present, including adhesion of the edges of the upper and lower eyelids (ankyloblepharon), abnormal smallness of the eyes (microphthalmia), or the formation of cysts in certain regions of the eyes (e.g., limbic dermoids).
In some instances, individuals with frontofacionasal dysplasia have additional physical abnormalities. For example, some may have benign (noncancerous), fatty tumors in the forehead area (frontal lipomas) or a widow’s peak, which is a “V-shaped” extension of the scalp hair onto the middle of the forehead.