autosomal recessive

This seems to be a subtype of the Ehlers-Danlos syndrome in which the ocular features are prominent.  The cornea is thin and can perforate following relatively minor trauma.  It is often misshapen as well resulting in keratoglobus and keratoconus.  The external appearance can suggest buphthalmos but intraocular pressure is normal.  The sclerae are bluish suggesting that the connective tissue defect is more widespread among eye tissues. The lens is not hypermobile, however.  This disorder differs from Ehlers-Danlos type VIA (225400) (sometimes called the ocular-scoliotic form) in which there is a defect in lysyl hydroxylase although the ocular phenotype has some similarities.

Dislocated lenses are the only significant ocular features of this disorder.  In one patient the lenses were said to be in normal position at 5.5 months of age but mild nasal subluxation of both lenses was present at 11 months.  In a series of 22 patients, 10 had dislocated lenses and one had spherophakia.  Lens dislocations occur early and maybe even congenitally in some cases as the diagnosis has been made in seven children before one year of age.  On the other hand it is not a consistent sign since the lenses were not dislocated in seven individuals who were examined specifically for this sign.

The term Bardet-Biedl is applied to a clinically and genetically diverse group of disorders, of which at least 21 entities (BBS1-BBS21) are recognized.  This discussion is generically relevant to all of the phenotypes since the retinal dystrophy is common to all.

A progressive rod-cone dystrophy is a cardinal feature of all forms of Bardet-Biedl syndrome.  However, a subset of patients have primary cone degeneration.  In at least some forms of this syndrome, the cause seems to be a defect in the cilia that impairs the intraciliary protein transport between the inner and outer segments of the photoreceptors.  Vision loss has an early onset and usually progresses rapidly with severe loss of central and peripheral vision by the second or third decade of life.  Night blindness may be evident by 7 or 8 years of age.  The ERG is not recordable even in early childhood.  Pigmentary changes in the retina are often labeled retinitis pigmentosa but they are atypical for the usual disease.  Early changes are more characteristic of atrophy with a paucity of pigment but later the bone spicule pattern of hyperpigmentation appears.  The macula can appear atrophic and sometimes has a bull's eye pattern.  Optic atrophy and retinal arteriole narrowing may be seen.  Bardet-Biedl syndrome is clinically similar to Biemond syndrome (210350) except for iris colobomas that occur in the latter disorder.

The major ocular manifestations of abetalipoproteinemia are in the retina which develops diffuse and sometimes patchy pigmentary changes often called atypical retinitis pigmentosa.  In other cases the picture resembles retinitis punctata albescens with perivascular white spots in the peripheral retina.  Night blindness is an early and prominent symptom with abnormal dark adaptation thresholds evident before fundus pigment changes are seen.  The ERG shows loss of rod function before that of cone function.  The macula may or may not be affected while peripheral fields are often severely constricted.  Loss of photoreceptors occurs throughout life and visual fields show progressive constriction, sometimes with central sparing.  A single case of bilateral disc swelling in a 9 year-old girl has been reported.

Macular corneal dystrophy is a progressive, bilateral disorder with increasing corneal cloudiness throughout life. The onset of corneal haze is variable.  It can be seen in infancy but usually becomes apparent in the second or later decades of life.  Visual impairment can be severe, especially by mid-life.  The stroma, Descemet membrane, and endothelium are involved as keratocytes and endothelial cells accumulate intracytoplasmic vacuoles of glycosaminoglycans.  Corneal thickness is reduced, presumably due to abnormally dense packing of collagen fibrils in the stroma.  The epithelium does not seem to be involved.

Based on immunohistochemical profiles of inclusions, as well as phenotypic differences, attempts have been made to distinguish at least three types of macular dystrophy, I, IA, and II.  This may not be justified as the same gene is involved, and especially since several types have been described within the same inbred family.  Most likely these are variations in the phenotypic expression of the same gene, a  feature of many genetic disorders.