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Chapter 66 – Corneal and External Eye Manifestations of Systemic Disease

Chapter 66 – Corneal and External Eye Manifestations of Systemic Disease

 

ANNA C. NEWLIN

JOEL SUGAR

 

 

 

 

 

DEFINITION

• Disorders with cornea and external eye manifestations as part of systemic syndromes.

 

KEY FEATURE

• Anterior segment anomalies as well as systemic abnormalities.

 

ASSOCIATED FEATURE

• Usually genetic defect with multisystem clinical findings.

 

 

 

INTRODUCTION

As seen in many sections throughout this book, the eye commonly exhibits manifestations of more widespread systemic disorders. Although these disorders are too numerous to discuss at length, this chapter presents in tabular form some of the conditions that involve the cornea and external eye. The grouping of these presentations is in some cases obvious and in others more arbitrary. In many, if not most, cases, the listings are incomplete, because the intention is to present only disorders that have corneal and external ocular findings. Many other disorders are discussed elsewhere in this book. Where it is appropriate and information is available, genetic localizations are provided.

CONGENITAL DISORDERS

Congenital disorders are nonmetabolic disorders present at birth that have generalized systemic findings as well as ocular abnormalities of the anterior portion of the eye. These groupings are arbitrary and may change as genetic information allows more specific categorizations. Some of the craniofacial malformation syndromes with associated corneal and external disease findings are given in Table 66-1 . These disorders usually are readily recognizable. Their management requires a multidisciplinary

 

TABLE 66-1 — CRANIOFACIAL MALFORMATION SYNDROMES WITH CORNEAL INVOLVEMENT

Syndrome

Ocular Manifestations

Systemic Manifestations

Gene Locus

Crouzon and Apert

Shallow orbits, decreased motility, secondary corneal exposure

Craniofacial malformation and syndactyly (Apert)

10q26[1]

Meyer-Schwickerath (oculodentodigital dysplasia)

Microphthalmos and microcornea

Syndactyly, dysplastic tooth enamel

6q22–q24[2]

Goldenhar (oculoauriculovertebral dysplasia)

Limbal dermoids, microphthalmos, anophthalmos, lid notching, blepharophimosis ( Fig.66-1 [3] )

Facial asymmetry, vertebral anomalies, ear deformities

 

Hallermann–Streiff

Microphthalmos, spontaneously resorbing cataracts, macular pigment changes, Coats’ disease

Facial malformation, hypoplastic mandible, short stature, skin atrophy

 

 

 

approach with involvement of ophthalmologists, facial plastic surgeons, neurosurgeons, and others.

CHROMOSOMAL DISORDERS

The chromosomal disorders are defined by the location of the abnormality in the genetic material ( Table 66-2 ). In the future, a more thorough understanding of the regulatory or other gene mechanisms involved will allow better interpretation of the widespread, multisystemic findings in these disorders (see Chapter 2 ). It is often striking how different chromosomal defects may lead to similar phenotypic abnormalities.

INHERITED CONNECTIVE TISSUE DISORDERS

Some of the inherited connective tissue disorders are given in Table 66-3 . More detailed discussions of these disorders are found elsewhere in this text (see Chapter 59 ).

 

 

Figure 66-1 Goldenhar’s syndrome. Pedunculated temporal limbal dermoid present in a patient who had Goldenhar’s syndrome. (With permission from Ziavras E, Farber MG, Diamond G. A pedunculated lipodermoid in oculoauriculovertebral dysplasia. Arch Ophthalmol. 1990;108:1032–3.)

 

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TABLE 66-2 — CHROMOSOMAL DISORDERS WITH CORNEAL MANIFESTATIONS

Genetic Findings

Ocular Manifestations

Systemic Manifestations

13q deletion

Hypertelorism, ptosis, epicanthal folds, microphthalmos, retinoblastoma

Microcephaly, facial malformation, absent thumbs

18p deletion

Ptosis, epicanthal folds, hypertelorism, corneal opacity, keratoconus, microphthalmos

Brachycephaly, growth retardation, mental retardation

18q deletion

Hypertelorism, epicanthal folds, nystagmus, corneal opacity, microphthalmos, corneal staphyloma, microcornea

Growth retardation, mental retardation, facial malformation, microcephaly

18r

Same as 18p deletion, 18q deletion

Growth retardation, mental retardation, facial malformation, microcephaly

4p deletion (Wolf–Hirschhorn syndrome)

Hypertelorism, ptosis, microphthalmos, strabismus, cataract

Growth retardation, microcephaly, micrognathia, hypotonia seizures

Ring D chromosome

Ptosis, epicanthal folds, microphthalmos, strabismus, nystagmus

Mental retardation, microcephaly, facial malformation

Turner syndrome (45 × 0)[4]

Ptosis, epicanthal folds, strabismus, rarely micro-cornea, blue sclera, corneal opacity

Female, short stature, webbed neck

Trisomy 13 (Patau syndrome)

Microphthalmos, corneal opacity, Peters’ anomaly, cataract, retinal dysplasia ( Fig. 66-2 )

Microcephaly, cleft lip and palate, low set ears

Trisomy 18 (Edwards syndrome)

Corneal opacity, ptosis, epicanthal folds, microphthalmos, colobomas, cataract, retinal dysplasia

Low birth weight; failure to thrive; brain hypoplasia; cardiac, gastrointestinal, renal, and musculoskeletal anomalies

Trisomy 21 (Down syndrome)

Shortened, slanted palpebral fissure, neonatal ectropion, later trichiasis and entropion, keratoconus, cataract

Cardiac defects, mental retardation, short stature, characteristic facies

Partial trisomy 22 (cat’s eye syndrome)

Microphthalmos, hypertelorism, colobomas

Mental retardation, microcephaly, cardiac anomalies, ear anomalies, anal atresia

 

 

 

 

TABLE 66-3 — INHERITED CONNECTIVE TISSUE DISORDERS WITH CORNEAL MANIFESTATIONS

Disease

Biochemical Defect

Gene Locus

Ocular Manifestations

Systemic Manifestations

Marfan syndrome[5]

Fibrillin-1 gene mutations

15q21.1

Megalocornea, lens subluxation, high myopia, retinal detachment

Long extremities, lax joints, aortic/mitral dilatation, aortic dissection

Osteogenesis imperfecta[6]

Type I procollagen

COL1A1

COL1A2

17q21.31–q22

7q22.1

Blue sclera, keratoconus, megalocornea, optic nerve compression

Bone deformities, otosclerosis, dental anomalies

Ehlers–Danlos syndrome type VIA [7]

Lysyl hydroxylase

1p36.3–p36.2

Blue sclera, keratoconus, keratoglobus, lens subluxation, myopia, ocular fragility to trauma

Skin stretching, scarring joint hypermobility, scoliosis

Ehlers–Danlos syndrome type VIB [7]

Normal lysyl hydroxylase

Unknown

Same as VIA

Same as VIA

 

 

 

 

 

 

 

 

Figure 66-2 Trisomy 13. A, An inferior nasal iris coloboma and leukokoria are present. B, A coloboma of the ciliary body is filled with mesenchymal tissue that contains cartilage (C); note the retinal dysplasia (R). Generally, in trisomy 13, cartilage is present in eyes less than 10?mm in size. C, A karyotype shows an extra chromosome in group 13 (arrow). (A, Courtesy of Shaffer DB. In: Yanoff M, Fine BS. Ocular pathology, 4th ed. London: Mosby; 1996. C, Courtesy of Drs. B.S. Emanuel and W.J. Mellman. In: Yanoff M, Fine BS. Ocular pathology, ed 4. London: Mosby; 1996.)

 

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TABLE 66-4 — DISORDERS OF PROTEIN AND AMINO ACID METABOLISM

Disorder

Enzyme Deficiency

Gene Locus

Metabolite Accumulated

Mode of Inheritance

Ocular Manifestations

Systemic Manifestations

Cystinosis[8]

Probable defect of lysosomal cysteine transport protein

17p13

Cystine

Autosomal recessive

All forms—conjunctival and corneal cystine crystal deposition (needle-shaped, refractile, polychromatic crystals in full thickness of peripheral corneal and anterior central stroma), band keratopathy, photophobia

Infantile and adolescent forms—patchy retinal abnormalities, occasional macular changes ( Fig.66-3 )

Infantile form, renal failure, death

Adolescent form, renal failure

Adult form, no renal failure

Tyrosinemia[9] type II (tyrosinosis, Richner–Hanhart syndrome)

Tyrosine transaminase deficiency

16q22.1–22.3

Tyrosine

Autosomal recessive

Dendritiform corneal epithelial changes (branches or snowflake opacities), red eye, photophobia

Palmar–plantar hyperkeratosis, mental retardation, growth retardation

Alkaptonuria[10]

Homogentisate-1, 2-dioxygenase

3q21–q23

Homogentisic acid

Autosomal recessive

Triangular patches of intrascleral pigmentation near insertion of horizontal rectus muscles, “oil-droplet” opacities in limbal corneal epithelium and Bowman’s layer, pigmented pingueculae, irregular pigmented granules in episclera, no functional changes

Joint pain and stiffness

Wilson disease[11]

Defective excretion of copper from hepatic lysosomes

13q14.3–q21.1

Copper

Autosomal recessive

Kayser–Fleischer ring, “sunflower” cataract ( Fig. 66-4 )[12]

Liver dysfunction, spasticity, behavior disturbance, nephrotic syndrome

Lattice dystrophy type II (Meretoja syndrome)[13]

Gelsolin gene defect

9q34

Amyloid

Autosomal dominant

Lattice dystrophy, ptosis, glaucoma

Progressive cranial neuropathy, cardiac disease

 

 

METABOLIC DISORDERS

A number of systemic metabolic disorders of genetic origin affect the anterior portion of the eye. These disorders usually are autosomal recessive, and a single enzyme deficiency accounts for the clinical manifestations. In many of these disorders, the specific gene locus has been determined, as has the biochemical defect. Unlike the corneal changes in many of the corneal dystrophies, the corneal changes in metabolic disorders may involve more than one layer of the cornea, affect the peripheral as well as the central cornea, and progress over time. The disorders are subdivided according to the biochemical group in which the abnormality is found.

Protein and Amino Acid Metabolic Defects

Protein and amino acid metabolic defects are listed in Table 66-4 . These disorders are quite diverse, both clinically and biochemically.

Mucopolysaccharidoses

The mucopolysaccharidoses ( Table 66-5 ) are a group of related disorders in which mucopolysaccharides or glycosaminoglycans are progressively accumulated in lysosomes. Glycosaminoglycans are carbohydrates made up of chains of uronic acids and amino and neutral sugars. These chains are joined to protein and form proteoglycans, the ground substance between

 

 

 

 

Figure 66-3 Cystinosis. A, Myriad tiny opacities give the cornea a cloudy appearance. B, Polarization of an unstained histological section of the cornea shows birefringent cystine crystals (C). E, Epithelium. (A, Courtesy of Shaffer DB. In: Yanoff M, Fine BS. Ocular pathology, ed 4. London: Mosby; 1996.)

 

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Figure 66-4 Wilson’s disease, Kayser-Fleischer ring. A, The deposition of copper in the periphery of Descemet’s membrane, seen as a brown color, partially obstructs the view of the underlying iris, especially superiorly. A “sunflower” (disciform) cataract is present in the lens of this patient who has Wilson’s disease. B, An unstained section shows copper deposition (arrow) in the inner portion of peripheral Descemet’s membrane. (Modified from Tso MOM, Fine BS, Thorpe HE. Kayser-Fleischer ring and associated cataract in Wilson’s disease. Am J Ophthalmol. 1975;79:479–88.)

 

 

TABLE 66-5 — THE MUCOPOLYSACCHARIDOSES

Disorder

Enzyme Deficiency

Metabolite Accumulated

Mode of Inheritance

Gene Locus

Ocular Manifestations

Systemic Manifestations

Mucopolysaccharidosis 1-H (Hurler syndrome) [14]

a-l-Iduronidase

Heparan sulfate Dermatan sulfate

Autosomal recessive

4p16.3

Corneal clouding, pigmentary retinopathy, optic atrophy, trabecular involvement

Gargoyle facies, mental retardation, dwarfism, skeletal dysplasia

Mucopolysaccharidosis 1-S (Scheie syndrome)

a-l-Iduronidase

Heparan sulfate Dermatan sulfate

Autosomal recessive

4p16.3

Corneal clouding, pigmentary retinopathy, optic atrophy, glaucoma

Coarse facies, claw-like hands, aortic valve disease

Mucopolysaccharidosis 1-H/S (Hurler–Scheie syndrome; Fig. 66-5 )

a-l-Iduronidase

Heparan sulfate Dermatan sulfate

Autosomal recessive

4p16.3

Corneal clouding, pigmentary retinopathy, optic atrophy ( Fig. 66-5 )

More severe than I-S, less severe than I-H

Mucopolysaccharidosis II (Hunter syndrome) [15]

Iduronate sulfate sulfatase (iduronate sulfatase)

Heparan sulfate Dermatan sulfate

X-Linked recessive

Xq28

Rare corneal clouding, pigmentary retinopathy, optic atrophy

Similar to I-H with less bony deformity

Mucopolysaccharidosis III (Sanfilippo syndrome)[16] [17]

A: heparan-S-sulfaminidase (heparan sulfate N-sulfatase)

B: a-N-acteylglucosaminidase (N-acetyl d-glucosaminidase)

C: acetyl-CoA-glucosaminidase-N, N-acetyltransferase

D: N-acetylglucosamine-6-sulfate sulfatase

Heparan sulfate

Autosomal recessive

17q25.3 17q21.1

 

12q14

Chr #14

All forms: clinically clear cornea, occasional slit-lamp corneal opacities (mucopolysaccharide accumulation in intracytoplasmic vacuoles in keratocytes, endothelium and epithelium), pigmentary retinopathy, optic atrophy

All forms: mild dysmorphism, progressive ementia

Mucopolysaccharidosis IV (Morquio syndrome) [18] [19]

A: galactose-6-sulfatase

B: ß-galactosidase

Keratan sulfate

Autosomal recessive

Autosomal recessive

16q24.3

3p21.33

Corneal clouding, optic atrophy

Severe bony deformity, aortic valve disease, normal intelligence

Mucopolysaccharidosis V (reclassified as mucopolysaccharidosis 1-S)

 

 

 

 

 

 

Mucopolysaccharidosis VI (Maroteaux–Lamy syndrome)

N-acetylgalactosamine-4-sulfatase

Dermatan sulfate

Autosomal recessive

5q11–q13

Corneal clouding, optic atrophy

Similar to I-H, but normal intellect

Mucopolysaccharidosis VII (Sly syndrome)

ß-Glucuronidase

Dermatan sulfate Heparan sulfate

Autosomal recessive

7q21.1

Corneal clouding

Similar to I-H

 

 

the collagen fibrils in the corneal stroma. Keratan sulfate (lumican) and chondroitin sulfate or dermatan sulfate (decorin) are found in the normal cornea. Dermatan sulfate is also found in corneal scars. In the mucopolysaccharidoses, deficiency in a catabolic enzyme results in accumulation of glycosaminoglycan. The excess of dermatan sulfate and keratan sulfate in the cornea produces corneal clouding, while excess heparan sulfate results in retinal and central nervous system dysfunction.

Sphingolipidoses

The sphingolipidoses also arise from dysfunction of catabolic enzymes that results in accumulation of sphingolipids ( Table 66-6 ).

 

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Figure 66-5 The mucopolysaccharidoses. The cornea is clouded diffusely in this case of Hurler-Scheie syndrome. (Courtesy of Shaffer DB. In: Yanoff M, Fine BS. Ocular pathology, ed 4. London: Mosby; 1996.)

 

 

Figure 66-6 Fabry’s disease. Verticillate changes in the cornea of a carrier.

 

 

TABLE 66-6 — THE SPHINGOLIPIDOSES

Disorder

Enzyme Deficiency

Gene Locus

Metabolite Accumulated

Mode of Inheritance

Ocular Manifestations

Systemic Manifestations

GM2 gangliosidosis II (Sandhoff disease)

Hexosaminidase B, HEX B chain

5q13

Ganglioside GM2

Autosomal recessive

Membrane-bound vacuoles within corneal keratocytes, cherry-red macula

Psychomotor retardation, hepatosplenomegaly

Metachromatic leukodystrophy (Austin’s juvenile form)[20] [21]

Arylsulfatase A isozymes

22q13.31-qter

Sulfatide

Autosomal recessive

Corneal clouding

Mental retardation, seizures

Fabry disease[22]

a-Galactosidase

Xq22

Ceramide trihexoside

X-Linked recessive

Conjunctival and retinal vascular tortuosity, white granular anterior subcapsular lens opacities, oculomotor abnormalities, whorl-like corneal epithelial changes (cornea verticillata; Fig. 66-6 )

Renal failure, peripheral neuropathy

 

 

 

 

TABLE 66-7 — THE DYSLIPOPROTEINEMIAS[23]

Disorder

Deficiency

Gene Locus

Metabolite Accumulated

Mode of Inheritance

Ocular Manifestations

Systemic Manifestations

Lecithin–cholesterol acyltransferase deficiency[24]

Lecithin–cholesterol acyltransferase

16q22.1

Free cholesterol

Autosomal recessive

Dense peripheral arcus, diffuse grayish dots in central stroma, no visual changes

Atherosclerosis, renal insufficiency

Fish eye disease (high-density lipoprotein lecthin–cholesterol acyltransferase)[25]

a-Lecithin–cholesterol acyltransferase

16q22.1

Triglycerides, very low density lipoproteins; low-density lipoproteins

Autosomal dominant

Progressive gray–white–yellow dot corneal clouding, increased corneal thickness

None

Tangier disease (analphalipoproteinemia)

High-density lipoprotein

9q22–q31

Triglycerides (low high-density lipoproteins, cholesterol and phospholipids)

Autosomal recessive

Fine dot corneal clouding, severe visual loss, incomplete eyelid closure, ectropion, no arcus

Lymphadenopathy hepatosplenomegaly, coronary artery disease

Hyperlipoproteinemia I (hyperchylomicronemia) [26]

Lipoprotein lipase

8p22

Triglycerides, chylomicrons

Autosomal recessive

Lipemia retinalis, palpebral eruptive xanthomata

Xanthomas

Hyperlipoproteinemia II hyper-ß-lipoproteinemia IIa hyper-ß-lipoproteinemia IIb

Thought to be defective or absent low-density lipoprotein receptors

 

Low-density lipoproteins, cholesterol

Low-density lipoproteins, very low density lipoproteins, cholesterol, triglycerides, hypertriglyceridemia

Autosomal dominant

Both forms; corneal arcus, conjunctival xanthomata, xanthelasma

Coronary artery disease

Hyperlipoproteinemia III (dys-ß-lipoproteinemia; broad ß-disease)

Defective remnant metabolism in the liver caused by an abnormality in apolipo-protein E

19q13.2

Very low density lipoprotein remnants, cholesterol, triglycerides

Autosomal recessive with pseudo dominance

Arcus, xanthelasma, lipemia retinalis

Peripheral vascular disease, diabetes mellitus

Hyperlipoproteinemia IV (hyperpre-ß-lipoproteinemia)

Unknown

 

Triglycerides, very low density lipoproteins, cholesterol usually normal

Autosomal dominant

Arcus, xanthelasma, lipemia, retinalis

Vascular disease, diabetes mellitus

Hyperlipoproteinemia V (hyperprelipoproteinemia and hyperchylomicronemia)

Unknown

 

Very low density lipoproteins, chylomicrons

Unknown

Lipemia retinalis, no arcus

Xanthomas, hepatosplenomegaly

 

 

A number of sphingolipidoses in which corneal abnormalities do not occur have been described but are not included in this discussion.

Dyslipoproteinemias

The dyslipoproteinemias ( Table 66-7 ) are an often vague group of disorders because of the large number of lipid metabolic processes that exist. They are characterized by accumulation of lipid in the cornea, in retinal blood vessels, or in the eyelid skin. Greater understanding of these disorders has led to the subdivision of some categories and more specific nomenclature based on the pathophysiological processes involved.

Mucolipidoses

The mucolipidoses are characterized by the presence of abnormalities in the carbohydrate moiety of both glycoprotein and glycolipid. Oligosaccharides accumulate, which results in changes similar to those seen in the mucopolysaccharidoses and the sphingolipidoses ( Table 66-8 ).

OCULAR ANATOMICAL DISORDERS

Although such a classification of disorders is not biochemically rational, it does provide a framework within which potential associations between disorders that involve both nonocular organs and the eye may be considered. The corneorenal syndromes are

 

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TABLE 66-8 — THE MUCOLIPIDOSES

Disorder

Enzyme Deficiency

Gene Locus

Metabolite Accumulated

Mode of Inheritance

Ocular Manifestations

Systemic Manifestations

Mucolipidosis I (dysmorphic sialidosis, Spranger syndrome)[27]

Glycoprotein sialidase (neuraminidase I)

6p21.3

Unknown

Autosomal recessive

Macular cherry-red spot, tortuous retinal and conjunctival vessels, spoke-like lens opacities, progressive corneal clouding

Coarse facies, hearing loss, normal IQ

Mucolipidosis II (I-cell disease)[28]

GluNac-1-phosphotransferase

4q21–q23

Increased plasma lysosomal hydrolases

Autosomal recessive

Small orbits, hypoplastic supraorbital ridges and prominent eyes, glaucoma, megalocornea, corneal clouding

Hurler-like facies, mental retardation

Mucolipidosis III (pseudo-Hurler polydystrophy) [29]

GluNac-1-phosphotransferase

4q21–q23

Increased plasma lysosomal hydrolases

Autosomal recessive

Corneal clouding

Milder growth and mental retardation

Mucolipidosis IV (Berman syndrome)

Possible ganglioside sialidase

19p13.3–p13.2

Sialogangliosides

Autosomal recessive

Corneal clouding, retinal degeneration

Slowed psychomotor development

Goldberg syndrome (galactosialidosis)

ß-Galactosidase Neuraminidase

20q13.1

Unknown

Autosomal recessive

Macular cherry-red spot, diffuse mild corneal clouding, conjunctival telangiectases

Seizures, mental retardation, hearing loss, hemangiomas

Mannosidosis[30]

a-d-Mannosidase

19cen–21q

Unknown

Autosomal recessive

No corneal abnormalities or mild corneal clouding, lens opacities

Coarse facies, mental retardation, hearing loss

Fucosidosis

a-l-Fucosidase

1p34

Unknown

Autosomal recessive

 

Coarse facies, mental retardation, angiokeratoma

 

 

 

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TABLE 66-9 — CORNEORENAL SYNDROMES

Syndrome

Gene Locus

Ocular Manifestations

Systemic Manifestations

Alport mainly X-linked dominant

Also X-linked recessive and autosomal recessive

Xq22.3

COL4A5

 

2q36–q37

COL4A3-COL4A4

Posterior polymorphous corneal dystrophy, juvenile arcus, pigment dispersion, lenticonus, retinal pigmentary changes

Renal failure, hearing loss

Cystinosis

17p13

See Figure 66-3

Infantile form: renal failure, death

Intermediate form: renal failure

Adult form: no renal failure

Fabry disease

Xq22

See Figure 66-6

Renal failure, peripheral neuropathy

Lowe syndrome (oculocerebrorenal)

Xq26.1

Corneal keloids, glaucoma, cataracts

Mental retardation, amino acid urea, renal tubular acidosis, angiokeratomas

Wegener granulomatosis

Nongenetic

Marginal keratitis, scleritis, episcleritis

Granulomatous vasculitis of lungs, kidneys, nasopharynx

WAGR

11p13

Superficial corneal opacity and vascularization, aniridia, glaucoma, foveal hypoplasia, optic nerve hypoplasia

Wilms’ tumor, mental retardation, craniofacial anomalies, growth retardation

Zellweger

2p15(PEX13)

1q22

12p13.3(PEX5)

7q21–q22(PEX1)

6q23–q24

Axenfeld’s anomaly, corneal clouding, glaucoma, retinal degeneration

Craniofacial anomalies, hypotonia seizures, retardation, hepatic degeneration, cystic kidneys, cardiac defects, early death

WAGR, Wilms’ tumor, aniridia, genital anomalies, and mental retardation.

 

 

 

 

TABLE 66-10 — HEPATOCORNEAL SYNDROMES

Syndrome

Gene Locus

Ocular Manifestations

Systemic Manifestations

Gaucher disease

1q21

Prominent pingueculae, white deposits in corneal epithelium, vitreous opacities, paramacular gray ring

Hepatosplenomegaly, bone pain, accumulation of glucocerebroside

Wilson disease

13q14.3–q21.1

Kayser–Fleisher ring (see Fig. 66-4 )

Liver dysfunction; neurological dysfunction with dysarthria, spasticity, behavior disturbances

Zellweger syndrome

7q21–q22

See Table 66-9

See Table 66-9

Alagille syndrome[31]

20p11.2–p12

Posterior embryotoxon, anterior chamber anomalies, eccentric or ectopic pupils, chorioretinal atrophy, retinal pigment clumping

Cholestatic liver disease, structural heart defects

 

 

a disparate group of disorders in which corneal abnormalities combine with renal disease ( Table 66-9 ). The hepatocorneal syndromes are less common ( Table 66-10 ). The cutaneous disorders with anterior segment ocular findings are numerous, and only a few are listed here (see Table 66-11 ). This tabular review serves to emphasize the frequent associations between systemic disorders and the cornea and external eye. Numerous other disorders exist but are not included in this summary.

CONCLUSION

This brief overview of systemic diseases with corneal involvement, even though incomplete, emphasizes the importance of taking into account the whole patient, not just the cornea or the eye. As our understanding of the basic mechanisms involved in the disorders discussed increases, these conditions will be important areas for new therapeutic interventions.

 

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TABLE 66-11 — CUTANEOUS DISORDERS

Syndrome

Gene Locus

Ocular Manifestations

Cutaneous/Systemic Manifestations

Basal cell nevus syndrome

9q22.3, 9q31, 1p32

Multiple basal cell carcinomas of the eyelid, hypertelorism

Multiple basal cell carcinomas, jaw cysts, bony anomalies

Xeroderma pigmentosum

3p25

Lid neoplasms, conjunctival and corneal neoplasia, corneal exposure, drying

Basal cell carcinoma, squamous cell carcinomas, and malignant melanomas develop in sun-exposed areas

Ichthyosis (multiple types)

1q21, 12q11–q13, 14q11.2, X922.32, 19p12-q12

Eyelid and lash scaling (all types), ectropion with corneal exposure (lamellar ichthyosis)

Scaly skin

Keratitis–ichthyosis–deafness syndrome

 

Keratoconjunctivitis with corneal pannus formation

Ichthyosis, deafness

Epidermolysis bullosa (numerous types)

1q32, 1q25–q31, 10q24.3

Corneal epithelial cysts, blebs, corneal erosions, corneal scarring, conjunctival bullae, eyelid deformities

Skin blistering, contractures in severe dystrophic type

Ectrodactyly–ectodermal dysplasia–clefting

7p11.2–q21.3

Dysplasia of meibomian glands, blepharitis, corneal pannus formation, corneal scarring

Lobster-claw deformity of hands and feet, ectodermal dysplasia, cleft lip and palate

Porphyria (numerous types)

 

Corneal conjunctival and eyelid scarring, scleral necrosis

Photosensitivity of skin

Richner–Hanhart syndrome (tyrosinemia type II)

16q22.1–q22.3

See Table 66-4

See Table 66-4

 

 

 

 

REFERENCES

 

1. Wilkie AO, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995;9:165–72.

 

2. Gladwin A, Donnai D, Metcalfe K, et al. Localization of a gene for oculodentodigital syndrome to human chromosome 6q22-q24. Hum Mol Genet. 1997; 6:123–7.

 

3. Ziavras E, Farber MG, Diamond G. A pedunculated lipodermoid in oculoauriculovertebral dysplasia. Arch Ophthalmol. 1990;108:1032–33.

 

4. Chrousos GA, Ross JL, Chrousos G, et al. Ocular findings in Turner syndrome. Ophthalmology. 1984;91:926–8.

 

5. Ramirez F. Fibrillin mutations in Marfan syndrome and related phenotypes. Curr Opin Genet Dev. 1996;6:309–15.

 

6. Willing MC, Pruchno CJ, Byers PH. Molecular heterogeneity in osteogenesis imperfecta type I. Am J Med Genet. 1993;45:223–7.

 

7. Hautala T, Byers MG, Eddy RL, et al. Cloning of human lysyl hydroxylase: complete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome 1p36.3-p36.2. Genomics. 1992;13:62–9.

 

8. Jean G, Fuchshuber A, Town MM, et al. High-resolution mapping of the gene for cystinosis, using combined biochemical and linkage analysis. Am J Hum Genet. 1996;58:535–43.

 

9. Natt E, Kida K, Odievre M, et al. Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II. Proc Natl Acad Sci U S A. 1992;89:9297–301.

 

10. Fernandez-Canon JM, Granadino B, Beltran-Valero de Bernabe D, et al. The molecular basis of alkaptonuria. Nat Genet. 1996;14:19–24.

 

11. Thomas GR, Roberts EA, Walshe JM, Cox DW. Haplotypes and mutations in Wilson disease. Am J Hum Genet. 1995;56:1315–9.

 

12. Tso MOM, Fine BS, Thorpe HE. Kayser-Fleischer ring and associated cataract in Wilson’s disease. Am J Ophthalmol. 1975;79:479–88.

 

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4 comments on “Chapter 66 – Corneal and External Eye Manifestations of Systemic Disease

  1. Good Kharma keeps the wheel turning…

    (…) My blog is PR2, click my source link and you will get a dofollow link there upon approval! Let’s share the Google love! (…)…

  2. this is a great marvelous work..after all,im sorry to inform you that i really got bored for the so much similarities between many syndromes and i hope you may find a way to make it more beneficial by attaching the common pathology of a group to their overall clinucal manifestations and add only the difference between the ..sincerely,….dr Emad Alaaedin,Egypt,Cairo….senior house officer in The national institute of ophthalmic medicine and surgery.

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