Ординатура / Офтальмология / Английские материалы / Pediatric Ophthalmology for Primary Care 3rd edition_Wright, Farzavandi_2008

Connective Tissue Disorders

Marfan Syndrome

Marfan syndrome is a connective tissue disorder that is inherited as an auto somal dominant trait and is the most common cause of subluxated lenses. See Chapter 18 on subluxated lens for further discussion.

Stickler Syndrome

Stickler syndrome is a heterogenous autosomal dominant collagen disorder with high penetrance and is associated with facial and skeletal abnormalities, high myopia, and a high incidence of retinal detachment. The vitreous is liq uefied with optically empty areas of vitreous veils and condensations. Other ocular findings include glaucoma and cataracts. The classic facial appearance includes malar hypoplasia with flattened midface, flattened nasal bridge, micrognathia, and cleft or high arched palate. The cleft palate is part of the Pierre Robin sequence, which occurs in other syndromes as well. Mitral valve prolapse occurs in approximately 50% of cases. A progressive arthrop athy is present in almost all patients, but it may be subtle and only show up on x ray films as flattening of the epiphyseal centers.

Ehlers Danlos Syndrome

There are various forms of Ehlers Danlos syndrome. The ocular form, or form VI, consists of blue, fragile sclera with spontaneous perforation of the globe, keratoconus, and angioid streaks. Angioid streaks are breaks in the Bruch membrane (the layer under the retinal pigment epithelium). Patients with Ehlers Danlos syndrome have thin, extensible skin, hyperextensibility of joints, and skin that scars easily.

Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum is an autosomal recessive disease that affects the elastic component of connective tissue. There is calcification of the elastic component of vessels and of the Bruch membrane. Because of the vascu lopathy, multiple systems are affected. Resultant systemic problems include coronary heart disease, renal failure and hypertension, neurologic disease, and gastrointestinal hemorrhages. Mitral valve prolapse occurs in more than 70% of cases. Skin is elastic and hyperextensible.

Ocular findings include angioid streaks that radiate peripherally from the optic disc. The elastic layer of the Bruch membrane is replaced by calcific changes, and subretinal neovascularization occurs as vessels grow through the breaks in the Bruch membrane. There is no specific treatment except for addressing complications of the vasculopathy and retinal neovascularization.

Osteogenesis Imperfecta

Osteogenesis imperfecta (OI), a disease of type 1 collagen alpha chains, affects connective tissue. There are at least 7 clinical subtypes, most of which (except type 7 and rare cases of type 3) show autosomal dominant inheritance. Three genes are associated with OI. Ocular signs include blue sclera resulting from visualization of the choroid through thin sclera. The scleral thickness in these patients is approximately half that of normal patients. Other ocular findings include keratoconus, megalocornea, and posterior embryotoxon. Rarely patients will have cataracts, glaucoma, and spontaneous rupture of the globe. Patients are prone to fractures of the long bones and spine. Dentinogenesis imperfecta and later onset hearing loss may occur.

Metabolic and Storage Diseases

Mucopolysaccharidosis

Mucopolysaccharidoses (MPS) are a group of storage diseases caused by an error of carbohydrate metabolism. At present, there are 6 different MPS syn dromes, all recessively inherited except Hunter syndrome, which is X linked. The classification of MPS into groups I to VI is based on the type of enzyme deficiency. Type V is presently vacant, as the former type V has been identi fied as a subtype of type I. Type I is subdivided into 3 categories based on the severity of the disease: type I H (Hurler syndrome), type I S (Scheie syn drome), and type I H/S (Hurler Scheie syndrome).

Table 24 5 summarizes the clinical features of the MPS syndromes.

Systemic and ocular features are variable and subtype specific. Typical systemic abnormalities include coarse facial features, short stature, and mental retardation (Figure 24 7). Hepatosplenomegaly may occur. Depend ing on the enzyme deficiency, various types of mucopolysaccharides can

be found in the urine. Common ocular findings include corneal stromal

Figure 24 7.

A, Typical Hurler facies. B, Slitlamp photo of cloudy cornea in mucopolysaccharidosis.

clouding, pigmentary retinal degeneration, and optic nerve atrophy. Corneal clouding usually coexists with skeletal abnormalities and is present in all types except type III. Pigmentary retinopathy is associated with the presence of mental retardation.

Mucopolysaccharidoses are progressive diseases with variable prognosis. Usually, patients live well into middle age except for patients with types I

and VI, who develop respiratory infection and heart failure at an earlier age. Patients with visually significant corneal opacities may benefit from corneal transplantation. There may in fact be clearing of the surrounding recipient corneal bed 1 or 2 years after transplantation. Enzyme replacement therapy improves some of the systemic manifestations of MPS types I, II, and VI.

Tyrosinemia

An error in tyrosine metabolism leads to high serum levels and increased urinary excretion of tyrosine and parahydroxyphenylpyruvate.

Tyrosinemia type 1 and neonatal tyrosinemia have no characteristic skin or eye lesions. Tyrosinemia type 2, or Richner Hanhart syndrome, presents a clinical triad of skin lesions, ocular manifestations, and mental retardation. The ocular features are typically seen as corneal lesions and appear early in childhood. Painful, erosive, or hyperkeratotic skin lesions over palms and soles coexist with, or precede, ocular lesions. Pseudodendritic corneal ero sions, culture negative ulcers, and intraepithelial linear or stellate opacities have been described.

Estimation of serum tyrosine levels is imperative in a child with bilat eral photophobia and pseudodendritic corneal lesions. Early detection and dietary restriction of phenylalanine and tyrosine lead to reversal of ocular and skin changes and even prevention of mental retardation.

Mucolipidosis

Some of the clinical features seen in this group of conditions overlap those found in MPS and sphingolipidoses. Mucolipidosis is characterized by the presence of peculiar inclusion cells (I cells) in cultured fibroblasts. A con junctival biopsy is diagnostic. Table 24 6 lists the clinical features of the subtypes.

Gangliosidosis

This rare group of storage disorders represents errors of sphingolipid metab olism. These are characterized by intracellular storage of phospholipids and glycolipids in the ganglion cell layer of retina, as well as other tissues of the body. The macula, being devoid of ganglion cells, presents a characteristic cherry red appearance against a white background of lipid laden ganglion

Table 24-6. Clinical Features of Mucolipidoses

cells and indicates the initial stage of the disease. Table 24 7 lists the differ ential diagnosis of a cherry red spot. Table 24 8 describes the salient features of the different subtypes of gangliosidoses.

Niemann Pick Disease

Niemann Pick disease is a disorder of sphingomyelin metabolism and is characterized by the presence of “foam cells” (intracellular deposits of sphin gomyelin) in bone marrow, peripheral blood smear, liver, spleen, and brain. These are classified into types A through E on biochemical and clinical basis and all present with a cherry red spot.

Type A: Most common (85%) and 80% are Ashkenazi Jews. They have early and severe central nervous system (CNS) involvement.

Type B: Visceral involvement with apparently normal CNS involvement. Type C: Moderate CNS involvement. Ocular features also include supra

nuclear paralysis of extraocular muscles.

Type D: Has later onset but severe involvement of CNS. Type E: Mild, chronic adult onset with no CNS involvement.

Table 24-7. Differential Diagnosis of a Cherry Red Spot

Gangliosidosis

Niemann-Pick disease

Farber disease

Sialidosis

Mucolipidosis

Ocular trauma

Central retinal artery occlusion

Sialidosis

In this condition, the enzyme neuraminidase is deficient. There are 2 types of sialidosis.

Type I: Myoclonus syndrome begins in the second decade of life in patients who otherwise have a normal appearance and normal intelligence. Type II: Patients have a more severe and progressive systemic involve ment. Corneal clouding, as well as cherry red spots, have been reported in

this subtype.

Farber Disease

Deficiency of ceramidase has been demonstrated in patients with Farber dis ease. They are known to also present with cherry red spots, in addition to the systemic features of lumps on wrists, ankles, and joints. In the infantile form of the disease, death occurs because of pulmonary complications. The adult onset group develops progressive neurologic disease.

Metachromatic Leukodystrophy

Metachromatic leukodystrophy is an autosomal recessive condition with deficiency of arylsulfatase A, leading to widespread demyelination of the brain and spinal cord. A classic cherry red spot has been described in addi tion to the finding of optic atrophy. Of the infantile, juvenile, adolescent, and adult forms, the infantile form is most common and has the worst prognosis.

Wilson Disease

Wilson disease is a rare condition that is characterized by widespread depo sition of copper due to the deficiency of alpha 2 ceruloplasmin. It is asso ciated with mutations in the gene ATP7B, a copper transporting ATPase. Kayser Fleischer ring, a golden brown ring of copper deposits at the level

of Descemet membrane in the cornea, is the most specific ocular finding and is present in all cases, although its appearance may be delayed in some children. Typically, it develops superiorly, then inferiorly, and finally in the horizontal meridian. It recedes in an identical manner after penicillamine therapy or liver transplantation.

Some patients also present with a green “sunflower” cataract. This is actually an anterior subcapsular deposit of granular pigment rather than a cataract. Copper deposition in the liver, spleen, and CNS can cause a wide spectrum of clinical presentations such as jaundice, hepatosplenomegaly, cerebral degeneration, and mental instability.

Fabry Disease

Fabry disease is due to the deficiency of the enzyme alpha galactosidase A. Despite X linked inheritance, females are affected, though generally less severely and later than males. In most cases, patients present with angio keratomas of skin and have episodes of excruciating pain in the fingers and toes. The most common ocular features are corneal verticillata, or whorl dystrophy of cornea, and a “Fabry cataract.” Corneal verticillata are bilateral, brownish deposits at the level of the Bowman membrane located inferiorly on the cornea. Corneal verticillata have also been described in patients

on antiarrhythmic agents and drugs such as indomethacin, chloroquine, and meperidine.

Fabry cataract is unique with spoke like granular lens opacities. Aneu rysmal dilatation of inferior bulbar conjunctival vessels has also been reported in 78% of cases. Common systemic features include angiokerato mas and cardiac and renal lesions. Enzyme replacement therapy improves many of the clinical symptoms and enhances quality of life for Fabry patients.

Cystinosis

Widespread systemic and ocular cystine crystal deposition occurs in this autosomal recessive disease, which maps to chromosome 17p13. The gene encodes an integral membrane protein, which has features of a lysosomal membrane protein. The gene is strongly expressed in pancreas, kidneys (mature and fetal), and skeletal muscle; to a lesser extent in placenta and heart; and weakly in lung and liver. The common sites include the kidneys,