Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Eye and Systemic Disease_Wright, Spiegel, Thompson_2006

TABLE 10-2. (continued).

Mucopolysaccharidosis Type VII Syndrome Sly Syndrome, Beta-Glucuronidase Deficiency MIM *253220 Gene map locus: 7q21.11. Inheritance: autosomal recessive. Over 20 cases reported.

General Description: beta-glucuronidase deficiency. Mild, intermediate, and severe forms. Growth deficiency, moderately severe mental deficiency, macrocephaly, coarse facies, short neck, joint contractures, radiologic signs of dysostosis multiplex, J-shaped sella turcica, thoracolumbar gibbus, hepatosplenomegaly, valvular hear disease, frequent respiratory infections, hearing loss, hydrocephalus, neurodegeneration (the neurological decline generally does not present until 3–4 years of age). Death may occur in the first few months of life. In the milder forms there is survival into adolescence.

Ocular Findings: hypertelorism, corneal clouding (in the severe form). Pigment retinopathy, optic nerve swelling, and optic atrophy have been reported.

Mulibrey Nanism Syndrome Perheentupa Syndrome, Dwarfism-Mulibrey Type

MIM #253250 Gene map locus: 17q22–q23. Inheritance: autosomal recessive. Over 40 cases reported.

General Description: short stature, triangular facies with frontal bossing, relatively small tongue, dental crowding, dolichocephaly with J-shaped sella turcica, thick adherent pericardium with pericardial constriction, hepatomegaly, prominent neck veins, muscle hypotonia, high-pitched voice

Ocular Findings: decreased retinal pigmentation with dispersion and clusters of pigment and “yellowish dots” in the midperipheral region, choroid hypoplasia

Multiple Lentigines Syndrome Leopard Syndrome MIM *151100 Inheritance: autosomal dominant. Over 70 cases reported.

General Description: multiple lentigines, mild pulmonic stenosis, hypertrophic obstructive cardiomyopathy, mild growth deficiency, mild to moderate sensorineural deafness, prominent ears, cryptorchidism

Ocular Findings: mild hypertelorism

Multiple Synostosis Syndrome Symphalangism Syndrome MIM 185650, *185700, 185750, #185800, *186400, #186500 Gene map locus: 17q22 (for #185800 and #186500). Inheritance: autosomal dominant. Fifty cases reported.

General Description: multiple fusion of midphalangeal joints, elbows, carpal and tarsal bones, multiple hand abnormalities, vertebral anomalies, fusion of middle ear ossicles with conductive deafness, hypoplasia of alae nasi

Ocular Findings: strabismus

Nager Syndrome Acrofacial Dysostosis 1, Nager Type MIM 154400 Gene map locus: 9q32. Inheritance: autosomal dominant. Over 75 cases reported.

General Description: Treacher Collins craniofacial abnormalities, with preaxial upper limb defects, hypoplastic thumbs, absent thumbs

Ocular Findings (as in Treacher Collins syndrome)

Common: lack of lateral canthal fixation causing drooping of the lower eyelid in an S-shaped contour. Colobomas or pseudocolobomas of the lateral third of the lower eyelid (75%). The medial part of the lower eyelid may be thin, absent of tarsal plate, and devoid of all marginal structures, including eyelashes and

(continued)

TABLE 10-2. Ocular and Systemic Findings in Selected Inherited Syndromes (continued).

meibomian glands (50%). “Egg-shaped” orbit caused by deformities of the temporal orbital wall. The relative protrusion of the nose may produce an enophthalmic appearance.

Less common: atresia of the lower lacrimal punctum and canaliculus, ptosis, distichiasis, trichiasis, ectropion, entropion, upper eyelid coloboma, microphthalmia, anophthalmos, pupillary ectopia, iris coloboma, cataract, corneal guttae

Nail-Patella Syndrome Onychoosteodysplasia MIM #161200 Gene map locus: 9q34.1. Inheritance: autosomal dominant. Over 400 cases reported. The disorder is caused by mutations in the LIM-homedomain protein LMX1B (*602575).

General Description: dysplasia of the nails and absent or hypoplastic patellae are the cardinal features of the syndrome. Abnormalities of nails include slow nail growth, hypoplastic to absent nails, longitudinal ridging, splitting (most commonly of thumbnail), discoloration, poorly formed and triangular (a unique finding) or absent lunulae (98%). The severity of the nail involvement is worse radial to ulnar. Toenails are involved in 1 of 7 individuals. Hypoplastic to absent patellae (60%–90%), patellar dislocation, hypoplasia of lateral femoral condyle and small head of fibula (92%), elbow deformities (60%–90%) with limited range of motion, hypoplasia of head of radius (90%), fifth finger clinodactyly, absence of distal phalangeal joints, talipes equinovarus, spur in midposterior ilium (iliac horn) (81%), hypoplasia of scapula (44%). Glomerulonephritis, nephrotic syndrome, renal insufficiency (48%). Occasionally, other musculoskeletal abnormalities, short stature, mental deficiency, psychosis, cleft lip/palate, hearing loss.

Ocular Findings

Common: open-angle glaucoma (reported in 9 of 28 families with the nail-patella syndrome). In most cases the glaucoma occurs in adulthood, but it can occur at any age.

Less common: keratoconus, microcornea, microphakia, cataract, ptosis. (These are sporadic abnormalities reported, not proven to be related to the disease.)

Neurofibromatosis, Type I (NF1) Von Recklinghausen Disease MIM *162200 Gene map locus: 17q11.2. Inheritance: autosomal dominant. Incidence: 1:2000–1:4000.

General Description: the disease is diagnosed when two or more of the following criteria are met: (1) six or more café au lait spots, measuring at least 1.5 cm in diameter in postpubescent individuals or 0.5 cm in diameter in prepubescent individuals; (2) two or more neurofibromas of any type or one plexiform neurofiboma; (3) freckling of axillary, inguinal, or other intertriginous areas; (4) two or more iris hamartomas (Lisch nodules); (5) optic glioma; (6) distinctive osseous lesions, such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudoartharoses, and (7) a first-degree relative with NF1 (according to the above criteria).Every system in the body may be affected by complications arising from NF1, and patients are at higher risk for malignancies.

TABLE 10-2. (continued).

Ocular Findings

Common: iris hamartomas (Lisch nodules) rarely seen before age 2 years, found in 92% over age 5 years, and in nearly 100% of patients over age 20 years. Lisch nodules are usually no larger than 1 mm, sharply demarcated, domeshaped excrescences. They consist primarily of uniform spindle-shaped melanin-containing cells.

Less common: chiasmal or optic nerve gliomas (optic glioma) (15%–19%). Symptomatic optic gliomas (producing complications such as visual loss, proptosis) occur in 1% to 5% of patients with NF1 and usually become symptomatic before the age of 10 years. Tumors confined to the optic nerve at the time of clinical presentation infrequently extend into the chiasm and very rarely develop metastases. There is almost no mortality with these tumors. Tumors primarily involving the chiasm may cause bilateral visual loss, hydrocephalus, and hypothalamic dysfunction. Mortality of 50% or higher has been reported with these tumors. Plexiform neurofibromas (30%) appear as extensive subcutaneous swellings with indistinct margins, and feel like a “bag of worms.” Approximately 10% of plexiform neurofibromas involve the face, commonly the upper eyelid and orbit causing ptosis, and an S-shaped configuration of the eyelid margin. Rarely malignant degeneration occurs within the lesion, producing a neurofibrosarcoma capable of metastasis. Glaucoma in the ipsilateral eye is found in as many as 50% of cases. Choroidal lesions (30%–50% of adults with NF1) are flat with indistinct borders, yellow-white to dark brown. NF1 patients are believed to be predisposed to developing uveal melanoma and other malignant neoplasms; however, the incidence of iris or choroidal tumors is low. Glaucoma (1%–2%) is associated in most cases with ipsilateral plexiform neurofibroma of the upper eyelid or with iris ectropion (ectropion uvea). Buphthalmos, enlargement of the cornea, corneal edema, and high myopia may result.

Neurofibromatosis Type II MIM *101000 Gene map locus: 22q12.2. Inheritance: autosomal dominant. Incidence: 1:33,000–40,000.

General Description: diagnostic criteria include bilateral vestibular schwannomas (called acoustic neuromas, although arising from the vestibular nerve rather than the acoustic nerve) (85%), or a first-degree relative with neurofibromatosis type II and either unilateral eighth nerve mass or two of the following: neurofibroma, meningioma, glioma, schwannoma, posterior capsular cataract, or other lens opacities at a young age.

Ocular Findings

Common: lens opacities (69%–80%): posterior subcapsular cataracts are the most common and usually develop during adolescence or young adulthood, peripheral cortical cataracts and other lens opacities have been associated with NF2, retinal astrocytic hamartomas (23%), juvenile-onset ocular motor paresis (12%)

Less common: small retinal scars, epiretinal membranes, juvenile-onset vitreoretinal degeneration (6%), retinal detachment, combined pigment epithelial and retinal astrocytic hamartomas, optic nerve sheath meningioma, Mittendorf dot, embryonal cataract, persistent hyperplastic primary vitreous, anisocoria, uveal melanoma, optic nerve head gliomas, myelinated nerve fibers, choroidal hamartoma, choroidal nevus, and choroidal hemangioma have been reported

(continued)

TABLE 10-2. Ocular and Systemic Findings in Selected Inherited Syndromes (continued).

Visual loss in NF2 is more commonly due to intracranial and optic nerve sheath meningioma than to cataract. Other causes of visual loss include combined pigment epithelial and retinal hamartomas, epiretinal membranes, chronic papilledema, and amblyopia due to ocular motor paresis.

Noonan Syndrome 1 Turner-Like Syndrome MIM *163950 Gene map locus: 12q24. Inheritance: autosomal dominant. Incidence: 1:1000–1:2500 live births.

General Description: short or webbed neck, low posterior hairline, shield chest and pectus excavatum or pectus carinatum or both, pulmonary valve stenosis, cryptorchidism, coagulation defects, postnatal growth deficiency (50%), mental retardation (25%), low-set and/or abnormal auricles, anterior dental malocclusion, increased width of mouth, prominent protruding upper lip, moderate retrognathia

Ocular Findings: epicanthal folds, ptosis, hypertelorism, down-slanting palpebral fissures, myopia, keratoconus, strabismus, nystagmus, blue-green irides

Norrie’s Disease Pseudoglioma MIM *310600 Gene map locus: Xp11.4–p11.3. Inheritance: X-linked. Over 200 cases reported.

General Description: microcephaly, severe and progressive mental retardation, psychosis, seizures, progressive sensorineural deafness (25%), which has its onset in the second or third decade of life, hypogonadism, cryptochidism

Ocular Findings: ocular signs are present at birth and include bilateral retinal folds, or retinal detachment and bilateral retrolental masses formed by dysplastic detached retinas. Shallow anterior chambers with dilated pupils, hypoplastic irises, posterior synechiae, and ectropion uvea. The ciliary processes are elongated and often visible through the pupil. The globes usually become phthisical. Other reported manifestations include pseudoglioma, cataract, and band-shaped corneal degeneration.

Oculocerebrorenal Syndrome Lowe Syndrome MIM *309000 Gene map locus: Xq26.1. Inheritance: X-linked recessive. Incidence: unknown.

General Description: growth retardation, fair skin, chubby cheeks, frontal bossing, severe mental retardation, areflexia, hypotonia, seizures, noninflammatory joint swelling, generalized proximal renal tubular dysfunction (renal Fanconi’s syndrome) develop during the first year of life producing renal wasting of water, bicarbonate, glucose, and amino acids. Patients present with polyuria and polydipsia. Calcium and phosphorus loss may result in bone resorption. Proteinuria may develop as renal failure ensues.

Ocular Findings: congenital cataracts of the nuclear, polar or complete type are characteristic and essential to the diagnosis. The lens tends to be small, thick, opaque, and disc shaped, with no demarcation between the nucleus and cortex. Posterior lenticonus may be demonstrated. The anterior capsule tends to be irregularly thickened, often with fibrous anterior subcapsular plaques. The posterior capsule is extremely thinned. The peripheral lens may show vacuolization, clefting, and focal opacifications. Congenital glaucoma (65%) is thought to be due to goniodysgenesis. Miotic pupils due to hypoplastic dilator muscle and hypertrophied sphincter muscle. Corneal keloids are common after 6 years of age and may contribute to visual impairment. Obligate carriers have characteristic multiple gray-white opacities in the cortex of the lens.

TABLE 10-2. (continued).

Oculodentodigital Syndrome Oculodentoosseous Dysplasia (ODOD) MIM *164200 Gene map locus: 6q22–q24. Inheritance: autosomal dominant. Approximately 85 cases reported.

General Description: enamel hypoplasia, microdontia or hypodontia, camptodactyly of fifth fingers, bilateral syndactyly of fourth and fifth fingers and third and fourth toes, midphalangeal hypoplasia or aplasia of one or more fingers and/or toes, thin nose with hypoplastic alae nasi and small nares, fine dry and/or sparse and slow-growing hair, broad tubular bones, and mandible with wide alveolar ridge. Occasionally cleft lip and palate, conductive hearing loss, and osteoporosis.

Ocular Findings

Common: “small eyes,” microcornea with otherwise normal ocular dimensions, microphthalmia, scarce eyebrows, narrow and short palpebral fissures, telecanthus, epicanthal folds, bony orbital hypotelorism with normal inner canthal distance

Less common: open-angle glaucoma or angle-closure glaucoma, various degrees of iris hypoplasia, cataract, strabismus

Glaucoma is the major cause of visual loss, with an onset ranging from infancy to adulthood; therefore, periodic ophthalmic evaluation is recommended.

Opitz Syndrome Type I, II Opitz–Frias Syndrome MIM *300000, *145410 Gene map locus: Type I, Xp22; Type II, 22q11.2. Inheritance: Type I, X-linked recessive; Type II, autosomal dominant. Over 30 cases reported.

General Description: mild to moderate mental deficiency, hypotonia, hypospadias, laryngotracheal abnormalities, swallowing difficulties with recurrent aspiration, stridorous respirations. Initial failure to thrive is followed by normal growth in survivors. Broad flat nasal bridge with anteverted nostrils, cleft lip with or without cleft palate, short frenulum of tongue, micrognathia, posterior rotation of auricles, congenital heart defects.

Ocular Findings

Common: hypertelorism, upwardor downward-slanting palpebral fissures, epicanthal folds

Less common: strabismus

Oral-Facial-Digital Syndrome 1 OFD Syndrome, Type I MIM #311200 Gene map locus: Xp22.3–p22.2. Inheritance: X-linked dominant. Over 160 cases reported.

General Description: corpus callosum agenesis on CT scan, mental retardation, clumsy gait, dysarthria, broad nasal root, small nostrils, hypoplasia of alae nasi, cleft jaw, midline cleft of upper lip, aberrant hyperplastic oral frenula, lobulate tongue, tongue hamartomas, irregular asymmetical cleft palate, digital asymmetry, syndactyly, brachydactyly, facial milia, spotty alopecia, polycystic kidneys, renal failure. Lethal in hemizygotes.

Ocular Findings: lateral displacement of inner canthi

Oromandibular-Limb Hypogenesis Spectrum Aglossia-Adactyly Syndrome MIM

103300 Inheritance: autosomal dominant. Incidence: less than 1:20,000 births.

(continued)

TABLE 10-2. Ocular and Systemic Findings in Selected Inherited Syndromes (continued).

General Description: brain defect, especially of cranial nerve nuclei, causing Möbius sequence, small mouth, micrognathia, hypoglossia, variable clefting or aberrant attachments of tongue, mandibular hypodontia, cleft palate, facial asymmetry, limb hypoplasia of varying degrees to the point of limb deficiency, syndactyly, adactyly, splenogonadal fusion. Problems with hyperthermia can occur in children with four-limb amputation.

Ocular Findings: cranial nerve palsies including Möbius sequence, telecanthus, lower eyelid defect

Osteogenesis Imperfecta Syndrome, Type I MIM #166200 Gene map locus: 17q21.31–q22, 7q22.1. Inheritance: autosomal dominant. Incidence: 3.5:100,000 live births.

General Description: hyperextensibile joints (100%), bone fractures (92%), postnatal onset growth deficiency (50%). Hypoplasia of dentin and pulp of teeth with translucency and yellowish or bluish-gray coloration, susceptibility to caries, irregular placement and late eruption of teeth, thin skin, easy bruising (75%), postnatal onset of mild limb deformity, primarily anterior or lateral bowing of femora, hearing impairment (35%) secondary to otosclerosis (usually first noted in third decade)

Ocular Findings

Common: partial visualization of the choroid gives the sclera a blue appearance Less common: ectopia lentis is rare, embryotoxon, keratoconus, megalocornea

Oto-Palato-Digital Syndrome, Type I Taybi Syndrome MIM *311300 Gene map locus: Xq28. Inheritance: X-linked. Approximately 30 cases reported.

General Description: moderate conductive deafness, frontal and occipital prominence, absence of frontal and sphenoid sinuses, facial bone hypoplasia, cleft palate, partial anodontia, broad distal digits with short nails, mild mental deficiency, short stature

Ocular Findings: hypertelorism with lateral fullness of the supraorbital ridges

Pachyonychia Congenita Syndrome, Type 1 MIM #167200 Gene map locus: 17q12–q21, 12q13. Inheritance: autosomal dominant. Several kindreds reported. (Pachyonychia congenita, recessive, MIM 260130, has been described in 3 cases.)

General Description: progressive thickening of nails with yellow-brown discoloration, pinched margins, and an upward angulation of distal tips (the nails may eventually become hypoplastic or absent), patchy to complete hyperkeratosis of palms and soles, callosities of feet, palmar and plantar bullae formation in areas of pressure, keratosis pilaris, epidermal cysts filled with loose keratin on face, neck, and upper chest, verrucous lesions on the elbows, knees and lower legs, leukokeratosis of mouth and tongue, scalloped tongue edge, erupted teeth at birth, lost by 4 to 6 months, early loss of secondary teeth, other teeth anomalies, hair anomalies, alopecia. An abnormality of cellmediated immunity with tendency to oral and cutaneous candidiasis. Occasionally mental retardation. Areas of chronic bullous formation should be followed for development of skin malignancy.

Ocular Findings: occasionally “corneal thickening,” cataract, bushy eyebrows

TABLE 10-2. (continued).

Pallister–Hall Syndrome MIM #146510 Gene map locus: 7p13. Inheritance: autosomal dominant. Sixteen cases reported.

General Description: holoprosencephaly with midline cleft lip and palate, arrhinecephaly, hypothalamic hamartoblastoma, panhypopituitarism, imperforate anus, postaxial polydactyly. The majority of patients have died by 3 years of age, usually of hypoadrenalism.

Ocular Findings: microphthalmia, coloboma

Pena–Shokeir Syndrome, Type 1 Fetal Akinesia Sequence MIM *208150 Inheritance: autosomal recessive. Several dozen cases reported.

General Description: neurogenic arthrogryposis, pulmonary hypoplasia, prenatal onset of growth deficiency, rigid expressionless face, poorly folded ears. Approximately 30% are stillborn.

Ocular Findings: hypertelorism, prominent eyes, telecanthus, epicanthal folds

Peters’ Anomaly–Associated with Other Ocular Defects MIM 603807, *116150 Gene map locus: 11p13 (603807). Inheritance: autosomal dominant (*116150). Incidence: unknown.

Ocular Findings: Peters’ anomaly consists of a central corneal leukoma, with corresponding defects in the posterior corneal stroma Descemet’s membrane, and endothelium and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea. The condition is bilateral in 60%–80% of cases. Associated ocular defects may include: microcornea, microphthalmia, anterior polar cataract, dysgenesis of the angle and iris, glaucoma, spontaneous corneal perforation, cornea plana, sclerocornea, colobomas, aniridia, congenital aphakia, persistence of the hyaloid system, and total posterior coloboma of the retina and choroids.

Peters’ Anomaly–Isolated Ocular Abnormality MIM #604229 Inheritance: autosomal recessive (can be caused by mutation in the PAX6 gene and in the PITX2 gene), occasional autosomal dominant transmission has been reported. Many of the cases are sporadic. Incidence: unknown.

Ocular Findings: Peters’ anomaly is a congenital central corneal leukoma, with corresponding defects in the posterior corneal stroma Descemet’s membrane, and endothelium and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea. The condition is bilateral in 60%–80% of cases. The visual prognosis depends on the degree of corneal opacification and on the severity of associated ocular malformations. Unilateral cases are usually associated with deep amblyopia. Congenital or postsurgical glaucoma is a major cause of visual loss in many cases. As many as 50% of patients with Peters’ anomaly eventually lose light perception.

Peters’ Anomaly with Short-Limb Dwarfism Kivlin-Krause Syndrome MIM *261540 Inheritance: autosomal recessive. Incidence: several reports of familial cases.

General Description: short stature, short hands, tapering brachydactyly, short fifth finger, fifth finger clinodactyly

(continued)

TABLE 10-2. Ocular and Systemic Findings in Selected Inherited Syndromes (continued).

Ocular Findings: Peters’ anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet’s membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (see Peters’ Anomaly—Isolated Ocular Abnormality, above)

Peters’-Plus Syndrome MIM *261540 Inheritance: autosomal recessive. Over 40 cases reported.

General Description: Peters’ anomaly occurs in association with cleft lip/palate, round face, depressed nasal bridge, anteverted nostrils, thin upper lip, mental retardation, abnormal ears, hearing loss, cerebral atrophy on CT scan, macrocephaly, hydrocephaly, hypoplastic female genitalia, cryptorchidism, cardiovascular anomalies, midline defects. Sixty percent of patients with Peters’ anomaly have systemic malformations or developmental delay. Patients with unilateral disease are as likely to have systemic malformations as patients with bilateral disease. Chromosomal studies should be obtained in those patients with multiple congenital malformations and Peters’ anomaly.

Ocular Findings: Peters’ anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet’s membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (see Peters’ anomaly—Isolated Ocular Abnormality, above). Narrow palpebral fissures.

Pfeiffer’s Syndrome, Type I, II, III Acrocephaloysyndactyly Type 5 MIM #101600 Gene map locus: 10q26, 8p11.2–p11.1. Inheritance: Type I is autosomal dominant. Types II and III are sporadic. Over 30 cases reported.

General Description: craniosynostosis results in turribrachycephalic skull, broad, short thumbs and great toes with radial deviation are characteristic, malformed proximal phalanx. Various internal organ anomalies have been reported, more frequent in type II and type III. Type I patients usually have normal intelligence and generally good outcome, whereas patients with Types II and III often have neurological involvement and shortened life expectancy.

Ocular Findings

Common: shallow orbits, proptosis, down-slanting palpebral fissures, hypertelorism, strabismus

Less common: ptosis, scleralization of the cornea, optic nerve hypoplasia, anterior chamber defects including Peters’ anomaly, bilateral superior iris coloboma (reported in one affected patient)

Progeria Syndrome Hutchinson–Gilford Syndrome MIM 176670 Inheritance: likely autosomal dominant. Incidence: 1:4,000,000–1:8,000,000.

General Description: precocious senility of striking degree is characteristic, death from coronary heart disease is frequent and can occur before 10 years of age, alopecia, atrophy of subcutaneous fat, skeletal hypoplasia and dysplasia, short stature

Ocular Findings: congenital or acquired cataract, microphthalmia

Proteus Syndrome MIM 176920 Inheritance: sporadic. Several dozen cases reported.

TABLE 10-2. (continued).

General Description: overgrowth that may involve the whole body, may be unilateral, may involve one limb or may be localized involving a digit or any combination of the above, macrocephaly, generalized thickening of skin, hyperpigmented areas that appear to represent epidermal nevi, lipomata, lymphangiomata, and hemangiomata, hemihypertrophy, bony prominences over skull, angulation defects of knees, scoliosis, kyphosis, vertebrae anomalies, hip dislocation, macrodactyly, soft tissue hypertrophy of hands and feet, cardiac and renal abnormalities

Ocular Findings: ptosis, strabismus, epibulbar dermoid, “enlarged eyes,” microphthalmia, myopia, cataract, nystagmus

Pseudo-Hurler Polydystrophy Syndrome Mucolipidosis Type III MIM *252600 Inheritance: autosomal recessive. Incidence: Unknown.

General Description: decreased growth rate in early childhood, mild mental deficiency, development of mildly coarse facies by 6 years, joint stiffness by 2 to 4 years, aortic valve disease, no mucopolysacchariduria. Some patients live into the fourth or fifth decade. A disorder similar to mucolipidosis II but milder (see mucolipidosis II). Lysosomal disorder resulting from deficiency of N-acetylglucosamine-1-phosphtransferase.

Ocular Findings: fine opacities of the corneal stroma, evident by 6 to 8 years of age (do not significantly affect vision), hyperopic astigmatism. epiretinal membranes, retinal vascular tortuosity and optic nerve head swelling have been reported

Radial Aplasia-Thrombocytopenia Syndrome TAR Syndrome MIM *274000 Inheritance: autosomal recessive. Over 100 cases reported.

General Description: thrombocytopenia, bilateral absence of radius, hypoplasia of ulna

Ocular Findings: nevus flammeus of forehead, strabismus, ptosis

Rapp–Hodgkin Ectodermal Dysplasia Syndrome Hypohidrotic Ectodermal Dysplasia, Autosomal Dominant Type MIM *129400 Inheritance: autosomal dominant. Approximately 25 cases reported.

General Description: hypohidrosis; thin skin with decreased number of sweat pores, sparse, fine hair, small dysplastic nails, hypodontia with small conical teeth, low nasal bridge, high forehead, small mouth with oral clefts, hypospadias. Occasional abnormalities include short stature, atretic ear canals, hearing loss, syndactyly. Predisposed to hyperthermia in early childhood, and frequent occurrence of otitis media.

Ocular Findings

Common: frequent occurrence of purulent conjunctivitis

Less common: ptosis, absent lacrimal puncta

Renal Tubular Acidosis II Renal Tubular Acidosis, Proximal, with Bilateral Glaucoma, Cataract, and Band Keratopathy MIM #604278 Gene map locus: 4q21. Inheritance: autosomal recessive. Over 8 cases reported.

General Description: mental retardation, growth deficiency, dental anomalies, renal tubular acidosis, hyperchloremic acidosis

(continued)

TABLE 10-2. Ocular and Systemic Findings in Selected Inherited Syndromes (continued).

Ocular Findings: bilateral cataract, bilateral glaucoma, band keratopathy, nystagmus, corneal opacities

Retinoblastoma, RB1 MIM *180200 Gene map locus: 13q14.1–q14.2. Inheritance: Inheritance of the predisposition to retinoblastoma is an autosomal dominant trait because the presence of a single mutant allele renders the cell susceptible to tumorgenesis. Tumor formation, however, is a recessive trait and requires the additional loss or inactivation of the remaining wild-type, or normal allele. Inactivation of the tumor suppressor genes plays a major role in the etiology or progression of the malignancy. A germiline loss of function (LOF) mutation at the RB1 locus can be heritable or spontaneous, but it always results in a genetic predisposition to retinoblastoma because of its presence in every cell in the body. The clinical result of a germline LOF mutation is bilateral/multifocal retinoblastoma. Somatic or nongenetic RB, caused by two spontaneous LOF mutations in the same retinoblast, is a rare event. Statistically, such a rare double hit in one cell would never occur more than once. The clinical result is a unilateral, unifocal nature of nongenetic retinoblastoma and an older age of onset (average 24 months for somatic RB, versus 12 months for genetic RB). Approximately 15% of sporadic unilaterally affected individuals are heterozygous at the RB1 allele and possibly did not receive the second LOF mutation in one or both eyes by chance alone. Incidence: 1:15,000–20,000.

Retinoblastoma is the most common malignant ocular tumor of childhood.

General Description: In children with the hereditary disease there is a high rate of second malignancies (up to 90% at 30 years of age with a peak incidence at age 13 years) including osteogenic sarcoma, leukemia, lymphoma, and Ewing sarcoma. Cleft palate has been reported. Trilateral retinoblastoma (3% of cases) is the association of bilateral retinoblastoma with midline brain tumors, especially pinealoblastoma.

Ocular Findings: retinoblastoma, retinomas, retinal calcifications. Leukocoria is the presenting feature in nearly 50% of cases and strabismus in 20%. Less common presentations include vitreous hemorrhage, hyphema, ocular or periocular inflammation, glaucoma, proptosis, and hypopyon. Growth patterns of retinoblastoma are endophytic and exophytic. Endophytic retinoblastoma arises from the inner retina and seeds the vitreous. Exophytic retinoblastoma arises from outer retinal layers and causes a solid retinal detachment. A variant of endophytic retinoblastoma is the diffuse infiltrating retinoblastoma.

Rieger’s Syndrome, Type I, II MIM #180500, *601499 Gene map locus: Type I, 4q25–q26; Type II, 13q14. Inheritance: autosomal dominant. Incidence: 1:200,000.

General Description: Type I is accompanied by facial, dental, umbilical, and skeletal abnormalities. Facial features include broad nasal root with maxillary hypoplasia, mild prognathism, and protruding lower lip. Dental anomalies include hypodontia and partial anodontia, most commonly absence of the central and lateral maxillary incisors. The remaining teeth have small crowns. Failure of involution of the periumbilical skin, umbilical hernia, inguinal hernia, hypospadias, anal stenosis. Rare associated findings include empty or enlarged sella turcica, growth hormone deficiency, and growth hormone deficiency with congenital parasellar arachnoid cyst, myotonic dystrophy. There is a rare association of Rieger anomaly with psychomotor retardation. Type II is accompanied by congenital hip anomalies, congenital heart defects, anal stenosis,