2. Median cleft facial syndrome (frontonasal dysplasia; hypertelorism of Greig). Widely spaced eyes, broad nasal root, cleft nose and premaxilla, V-shaped frontal hairline, heterotypic anterior frontal fontanel (midline cranial defect); mild to severe cognitive impairment.
3. Chondrodystrophia calcificans congenita (chondrodysplasia punctata, Conradi-Hünermann syndrome). Prominent forehead; flat nose; widely separated eyes; short neck and trunk with kyphoscoliosis; dry, scaly, atrophic skin; cicatricial alopecia; irregularly deformed vertebral bodies; cognitive impairment infrequent. Severe shortening of limbs is seen in some cases.
4. Orofaciodigital syndrome. All the patients are female; they have pseudoclefts involving the mandible, tongue, maxilla, and palate; hypertrophied buccal frenula; hamartomas of tongue; sparse scalp hair; cognitive impairment in one-half of cases.
5. Pyknodysostosis. Large head and frontal-occipital bossing, underdeveloped facial bones, micrognathia, unerupted and deformed teeth, dense and defective long bones with shortened limbs, short and broad terminal digits of fingers and toes, cognitive impairment in one-quarter of the cases.
6. Craniotubular bone dysplasias and hyperostoses. Included under this title are several different genetic disorders of bone, characterized by modeling errors of tubular and cranial bones. Frontal and occipital hyperostosis, overgrowth of facial bones, and widening of long bones occur in various combinations. Hypertelorism, broad nasal root, nasal obstruction, seizures, visual failure, deafness, prognathism, and retardation of growth are the major features.
In this category of anomalies, there is simultaneous failure or imperfect development of eye and brain. One member of this group, the oculocerebrorenal syndrome of Lowe, has already been mentioned and, of course, many of the mucopolysaccharidoses are characterized by corneal opacities, skeletal changes, and psychomotor regression as considered separately in Chap. 36. Also, congenital syphilis, rubella, toxoplasmosis, and CMV inclusion disease may affect retina and brain; hypoxia at birth requiring treatment with oxygen may injure the brain and lead to retrolental fibrodysplasia. The true developmental defects in this group are as follows: 1. Anophthalmia with mental retardation. Sex-linked recessive. Absent eyes; orbits and maxillae remain underdeveloped, but adnexal tissues of eyes (lids) are intact; cognitive impairment. Some cases of anophthalmia have been ascribed to genes encoding transcription factors that play a role in the development of the neuraxis (SOX2, RAX, RAX6).
2. Norrie disease. Also sex-linked recessive; some sight may be present at birth; later, eyes become shrunken and recessed (phthisis bulbi); some have short digits, outbursts of anger, hallucinations, and possibly regression of psychomotor function. A mutation in the NDP gene on the X chromosome has been implicated.
3. Oculocerebral syndrome with hypopigmentation. Autosomal recessive with absence of pigment of hair and skin; small, cloudy, vascularized corneas and small globes (microphthalmia); marked cognitive impairment; athetotic movements of limbs.
4. Microphthalmia with corneal opacities, eccentric pupils, spasticity, and severe cognitive impairment.