Table 2. Disorders associated with both ocular and neurologic impairment.

[This table is from: Leffler CT. Visual impairment. In: Accardo PJ (ed). Developmental disabilities in infancy and childhood. Johns Hopkins Univ. Press. Balto., MD 2007. pp 501-520.
It is very far down on the web page, so keep scrolling down. It originally was four columns, but it is only completely displayed on this website if it is reformatted to one column.]

Table 2. Disorders causing both ocular and neurological impairment.

Disorder.
Etiology/Inheritance.
Eye findings.
Other findings.
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ASSOCIATED WITH PIGMENTARY RETINOPATHY.
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Alstrom syndrome.
AR. Chromosome 2p13. (Hearn 2002).
Cone-rod retinal dystrophy.
SNHL, diabetes mellitus, obesity, dilated cardiomyopathy.
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Bassen-Kornzweig syndrome (abetalipoproteinemia)
Abetalipoproteinemia. Mutation in microsomal triglyceride transfer protein gene.
Retinitis pigmentosa. Restrictive ocular motility.
Spinocerebellar ataxia. Acanthocytosis. Celiac disease. Diarrhea.
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Cockayne syndrome.
AR. Chromosome 5 (Cockayne syndrome type A gene) or chromosome 10 (helicase).
Pigmentary retinal degeneration. Cataracts. Optic atrophy.
MR, dwarfism, deafness, progeria, photosensitive rashes.
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Kearns-Sayre syndrome.
Usually sporadic. Mitochondrial DNA deletion.
Progressive external ophthalmoplegia after age 5. “Salt and pepper” pigmentary retinopathy with normal arterioles. Rarely bone spicules. Nyctalopia. Ptosis. Onset under age 20, possibly in infancy. Ptosis.
Heart block, SNHL, vestibular dysfunction, cerebellar ataxia, corticospinal dysfunction, muscular dystrophy, MR, spongiform CNS degeneration. Short stature. Diabetes mellitus. SNHL. Treat with coenzyme Q10.
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Laurence-Moon-Bardet-Biedl syndrome.
AR. Multiple loci.
Retinitis pigmentosa.
MR, polydactyly, obesity, hypogenitalism, paraplegia.
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Neonatal adrenoleukodystrophy.
AR. Multiple lysosomal gene mutations (Mole 1999).
AR.
Cataract, optic atrophy, pigmentary retinopathy.
Psychomotor retardation. MR. Seizures. Adrenal insufficiency.
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Neuronal ceroid lipofuscinosis (Batten disease).
Pigmentary retinal degeneration. Optic atrophy. ERG extinction.
Cerebral atrophy. Ataxia. Seizures. Dementia.
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Olivopontocerebellar atrophy (a spinocerebellar ataxia).
AD. SCA-1 and SCA-2 genes on chromosomes 6 and 12, respectively. (Koeppen 1998).
Pigmentary retinal degeneration. Nystagmus. Slow saccades. Optic atrophy.
Cerebellar and brainstem atrophy. Dementia. Dysphagia. Dysarthria.
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Refsum disease.
AR. Phytanic acid accumulation due to phytanoyl CoA hydroxylase deficiency.
Retinitis pigmentosa. Optic atrophy.
Ataxia, polyneuropathy, Deafness, anosmia. Distal extremity weakness. Cardiac arrhythmias.
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Usher syndrome.
AR.
Retinitis pigmentosa.
SNHL. Type 1 (ataxia). Type 2 (no ataxia, less severe SNHL).
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Zellweger (hepatocerebrorenal) syndrome.
Abnormality in peroxisomal enzymes on chromosomes 8, 1, or 7. AR.
Infantile pigmentary retinal degeneration, nytagmus. Hypertelorism. Cataract. Microphthalmia.
Psychomotor retardation. Hypotonia. Seizures. Dysmorphic features. Renal cortical cysts. Hepatosplenomegaly.
==========
METABOLIC STORAGE DISEASES.
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Fabry disease (Angiokeratoma corporis diffusum).
XR. Alpha-galactosidase-A deficiency. Xq22. Accumulation of glycosphingolipids, including globotriaosylceramide.
Cream-colored corneal verticillata. Posterior spokelike subcapsular, punctate, or wedge-shaped cataracts. Conjunctival or retinal vascular abnormalities. Normal vision.
Cutaneous angiokeratomas, hypohydrosis, acral pain and paresthesias, renal cysts and failure. Myocardial ischemia. Febrile crises. Cerebral ischemia or hemorrhage. Seizures.
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Generalized gangliosidosis (GM1 gangliosidosis type I).
AR. Beta-galactosidase deficiency. Chromosome 3. (Suzuki 1991).
Foveal cherry red spot. Optic atrophy. Corneal clouding.
Developmental delay/arrest. Neurologic deterioration. Hepatosplenomegaly. Skeletal dysplasia.
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Mucolipidosis type I (cherry red spot-myoclonus syndrome).
AR. Neuraminidase (sialidase) deficiency. Chromosome 6. (Bonten 2000).
Foveal cherry red spot. Optic atrophy. Corneal opacities. Lamellar cataracts.
Ataxia. Myoclonic epilepsy. Hepatosplenomegaly.
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Mucopolysaccharidosis I-H (Hurler syndrome) and I-S (Scheie syndrome)
AR. Deficiency of lysosomal alpha-L-iduronidase with accumulation of dermatan sulfate and heparin sulfate. Chromosome 4. (Scott 1990).
Retinal pigmentary degeneration with spiculated appearance. Optic atrophy. Progressive corneal opacity without edema. ERG abnormalities.
MR, coarse facies, short stature. Joint stiffness. Dysostosis multiplex. Rhinitis. Enlarged tongue. Type I-S is less severe than type I-H.
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Mucopolysaccharidosis II (Hunter syndrome)
XR.
Retinal pigmentary degeneration with arteriolar narrowing. Optic atrophy. Corneal clouding. ERG abnormalities.
MR, coarse facies, short stature.
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Mucopolysaccharidosis III (Sanfilippo syndrome)
AR.
Retinal pigmentary degeneration with speculated appearance. Optic atrophy. Corneal clouding. ERG abnormalities.
MR, coarse facies, short stature.
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Niemann-Pick disease.
AR. Sphingomyelinase deficiency. Chromosome 11p15. Sphingomyelin accumulation in lysosomes of macrophages.
Foveal cherry red spot (primarily in type A). Anterior capsular brownish opacification and posterior capsular cataract.
MR in infantile (type A). Lung disease. Hepatosplenomegaly. Short stature. Pancytopenia.
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Sandhoff’s disease (GM2 gangliosidosis type II)
AR. Hexosaminidase A and B deficiency. Chromosome 5.
Foveal cherry red spot.
MR. Muscle weakness. Hepatosplenomegaly.
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Tay-Sachs disease (GM2 gangliosidosis type I).
AR. Hexosaminidase A deficiency. Chromosome 15. (Kaback 2001).
Foveal cherry red spot. Optic atrophy. Abnormal visual evoked responses.
MR. Muscle weakness. Seizures.
==========
PHAKOMATOSES.
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Angiomatosis retinae (von Hippel-Lindau disease).
AD. Chromosome 3.
Retinal capillary hemangiomas with dilated feeder vessels and associated hemorrhage or exudates.
Cerebellar hemangioblastomas, renal cell carcinomas. Cysts in pancreas, liver, epididymis, or ovaries. Pheochromocytoma.
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Ataxia-telangiectasia (Louis-Bar syndrome).
AR. Chromosome 11.
Oculomotor apraxia, bulbar conjunctival telangiectasias.
Mental retardation, progressive cerebellar ataxia in second year of life, skin telangiectasias, thymus hypoplasia, poor immune function, increased incidence of leukemia and lymphoma.
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Encephalofacial angiomatosis (Sturge-Weber syndrome).
Sporadic occurrence.
Choroidal hemangiomas. Glaucoma ipsilateral to eyelid or conjunctiva hemangiomas.
Seizure, mental retardation. CNS and meningeal hemangiomas. Facial hemangioma. Nevus flammeus present at birth.
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Neurofibromatosis type 1 (von Recklinghausen’s disease).
AD. Chromosome 17.
Lisch nodules (iris hamartomas) in almost 100% of type 1 by age 21. Relatives should be examined for Lisch nodules. Optic nerve glioma, glaucoma, conjunctival neurofibromas, enlarged corneal nerves, pulsatile proptosis.
MR, learning disabilities, seizures, neurofibromas, axillary and inguinal freckling, sphenoid hypoplasia, glioma, pheochromocytoma.
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Neurofibromatosis type 2.
AD. Chromosome 22.
Posterior subcapsular cataracts. Optic nerve gliomas and meningiomas.
Vertigo, seizures, mental retardation, acoustic neuromas, hearing loss, CNS glioma, meningioma, pheochromocytoma.
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Racemose angioma (Wyburn-Mason syndrome).
Sporadic occurrence.
Retinal arteriovenous anastomoses.
Mental retardation. Intracranial, especially midbrain, arteriovenous malformations with calcification.
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Tuberous sclerosis (Bourneville’s disease).
AD. Chromosome 9.
Retinal or optic nerve astrocytic hamartoma.
Seizures, mental retardation possible, CNS astrocytic hamartomas, achromic nevi (ash-leaf spots), café-au-lait spots, shagreen patches, visceral hamartomas in kidneys, bone, and heart.
==========
OTHER GENETIC CONDITIONS:
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Aicardi syndrome.
Optic nerve hypoplasia. Clear retinal lacunae.
Seizures. Infantile spasms. MR. Lethal in boys. Seen only in girls. Absence of corpus callosum. Gray matter abnormalities on MRI.
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Albinism.
AR (Chediak-Higashi syndrome). Tyrosinase-negative in complete oculocutaneous form.
Foveal and optic nerve hypoplasia, nystagmus, reduced visual acuity, iris transillumination defects, refractive errors, strabismus, decreased proportion of uncrossed fibers at optic chiasm.
MR and immune defects (in Chediak-Higashi syndrome).
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Aniridia.
2/3 AD, 1/3 sporadic chromosome 11 deletion.
Iris hypoplasia or absence, nystagmus, anterior polar or disk-like cataracts, foveal hypoplasia, glaucoma
MR, Wilms tumor in sporadic patients.
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Cornelia de Lange syndrome.
Usually sporadic. Rarely AD or AR.
Common: myopia, ptosis, nystagmus. Also: Optic atrophy, optic nerve colobomas, microcornea, astigmatism, microcornea, strabismus.
Prematurity. Intrauterine growth retardation. Low-pitched weak cry. Initial hypertonicity. MR.
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Down’s syndrome.
Trisomy 21.
Strabismus, nystagmus, keratoconus, total or punctate “snowflake” cataracts, myopia, astigmatism, glaucoma, ptosis, Brushfield spots (yellow iris spots). Epicanthal folds. Eyelid laxity.
MR. Large tongue. Facial hypoplasia. Short and webbed neck. Short digits. Palmar crease. Congenital heart disease.
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Friedreich’s ataxia.
AR. FRDA gene on chromosome 9, which encodes frataxin (Bradley 2000).
Optic atrophy. Nystagmus.
Spinocerebellar degeneration. Ataxia. SNHL.
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Galactosemia.
AR. Defect of galactose-1-phosphate uridyl transferase at chromosome 9p13.
Oil droplet, lamellar, nuclear, or total cataract shortly after birth in 75%.
Lethargy, hypotonia, hepatomegaly, sepsis, poor growth, language deficits. Treat with galactose restriction.
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Homocystinuria.
AR. Deficiency of cystathionine synthase with accumulation of homocysteine. Chromosome 21q22.3 (Kraus 1994).
Myopia, lens subluxation, cataracts, glaucoma, pigmentary retinal degeneration.
MR, marfanoid appearance, thromboembolism, leg weakness.
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Joubert syndrome.
AR.
Congenital retinal dystrophy. Oculomotor abnormalities.
Cerebellar hypoplasia, ataxia, MR, episodic hyperventilation.
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Leber congenital amaurosis.
AR rod-cone dystrophy.
Poor vision. Sluggish pupillary responses. Large-amplitude nystagmus within first few months. Eye pressing (ocular digital sign). Retina normal initially, then with vessel attenuation, optic disc pallor, retinal pigment changes. Hyperopia. Keratoconus. Abnormal or absent ERG.
MR, seizures. SNHL in 5%.
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Lowe (oculocerebrorenal) syndrome.
AR or XR. Decreased renal ammonia production.
Cataracts, glaucoma. Carriers have punctate cortical opacities.
Hypotonia, mental retardation, rickets, aminoaciduria.
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Myotonic dystrophy (Steinert disease)
AD.
“Christmas tree” or posterior subcapsular cataract.
Swallowing and speech disability. Muscle wasting.
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Septooptic dysplasia (de Morsier syndrome).
Usually sporadic. Can be AR. Hesx1 gene mutations (Bennett 2002).
Optic nerve hypoplasia.
Absence of septum pellucidum and agenesis or thinning of the corpus callosum. Pituitary abnormalities. Encephalocele. Brain MRI and endocrine evaluation warranted.
==========
CONGENITAL INFECTIONS AND TOXINS.
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Cerebral palsy.
Multiple etiologies: genetic, toxic, infectious, vascular insufficiency.
Strabismus, optic atrophy, nystagmus, refractive errors (Ashwal 2004).
Posture or movement disorder due to lesion of the developing brain.
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Congenital cytomegalovirus infection.
Maternal infection with cytomegalovirus.
Chorioretinal inflammation, retinal hemorrhage.
MR. Intrauterine growth retardation. Hepatosplenomegaly. Petechiae. Cerebral atrophy. Cerebal calcifications. SNHL. 1% of newborns.
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Fetal alcohol syndrome.
Maternal ethanol ingestion.
Small palpebral fissures (blepharophimosis), ptosis, telecanthus, anterior segment dysgenesis, strabismus, corneal opacities, optic nerve hypoplasia, retinal vascular tortuosity.
Cognitive impairment. Congenital heart disease. Facial abnormalities with absence of a philtrum and a broad upper lip.
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Herpes simplex, intrauterine.
Intrauterine disease less likely than transplacental acquisition.
Chorioretinitis, microphthalmia.
Encephalitis.
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Rubella, congenital.
Maternal infection during first trimester.
“Salt and pepper” retinopathy, nuclear or total cataract, glaucoma, microphthalmos.
Cardiac defects, deafness.
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Syphilis, congenital.
Transplacental passage of Treponema pallidum.
Choroiditis.
Hepatosplenomegaly. Pneumonia. Rhinitis. Neurosyphilis. Skin lesions.
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Toxoplasmosis, congenital.
Maternal infection with toxoplasma gondii.
Retinochoroiditis, focal atrophic and pigmented scars. Focal vitritis.
Cerebral calcifications. Convulsions. Fever. Hydrocephalus. Microcephaly.
==========

Abbreviations: AR = autosomal recessive. MR=mental retardation. SNHL=sensorineural hearing loss. XR=X-linked recessive. XD=X-linked dominant.

[This table is from: Leffler CT. Visual impairment. In: Accardo PJ (ed). Developmental disabilities in infancy and childhood. Johns Hopkins Univ. Press. Balto., MD 2007. pp 501-520.]


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