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

TABLE 10-2. (continued).

General Description: only 5%–10% survive the first year of life. Feeble fetal activity, polyhydramnios, growth deficiency, mental deficiency, low-set auricles, small oral opening, clenched hand, short sternum, low arch dermal ridge patterning on fingertips, ventricular septal defect, cryptorchidism, hirsutism.

Ocular Findings

Common: hypoplastic supraorbital ridges, ptosis, blepharophimosis, epicanthus, hypertelorism

Less common: nystagmus, anisocoria, strabismus, corneal opacities, uveal and optic nerve colobomas, optic nerve hypoplasia or gliosis, cataract, ciliary process abnormalities, microphthalmia, anophthalmia, myopia, retinal folds, congenital glaucoma, malformations of the iris pigment, stroma, sphincter, and dilator. Hypopigmentation of the posterior pole retinal pigment epithelium, neural retinal immaturity, focal areas of retinal dysplasia. Trisomy 18 is the second most common chromosomal aberration associated with microphthalmia or anophthalmia. Thickened or bluish sclera, scleral icterus, persistent hyperplastic primary vitreous, congenital aphakia, congenital unilateral facial paralysis, and ankyloblepharon have been described.

Trisomy 21, Down Syndrome MIM #190685 Trisomy for all or a large part of chromosome 21. Incidence: 1:660 live births.

General Description: hypotonia, mental deficiency, brachycephaly with relatively flat occiput and tendency toward midline parietal hair whorl, mild microcephaly, short nose with low nasal bridge, flat facies, a large protruding tongue, up-slanting palpebral fissures (“mongoloid slant”), small ears, short thick neck, loose skin folds in posterior neck in infancy, fine soft hair, cardiac anomalies, primary gonadal deficiency, higher incidence of leukemia, stubby hands with a single palmar crease, clinodactyly of fifth digit with hypoplasia of middigital phalanges, short stubby feet with a wide gap between first and second toes.

Ocular Findings

Common: up-slanting palpebral fissures (“mongoloid slant”), epicanthal folds, chronic xeroderma can affect the periorbital area and eyelids, syringomas which have a predisposition for the periorbital area. Refractive error, mostly myopia (70%), lens opacities in children ranging from visually insignificant fine cortical lens opacities to significant dense total congenital cataract (20%–60%), premature development of nuclear sclerosis (30%–60%), strabismus (45%), nystagmus (35%), Brushfield spots (30%–90%), peripheral hypoplasia of iris, blocked tear duct (20%).

Less common: keratoconus (6%–15%), congenital cataract (3%). Optic nerve hypoplasia, a characteristic “spoke wheel” disc (the vessels radiate out from the disc at multiple “clock” hours), crowded disc, bilateral lens subluxation.

Usher Syndrome Type I (A to F), II (A, B, C), Type III MIM IA *276900, IB *276903, IC #276904, IC *605242, ID #601067, IE *602097, IF *602083, IIA *276901, IIB *276905, IIC *605472, III *276902 Gene map locus: IA, 14q32, IB, 11q13.5, IC, 11p15.1, ID, 10q21–q22, IE, 21q21, IF, chr.10, IIA, 1q41, IIB, 3p24.2–p23, 2C, 5q14–q21, III, 3q21–q25. Inheritance: autosomal recessive. Incidence: 1:33,000. 50% of all patients deaf and blind likely have Usher syndrome.

(continued)

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

General Description: Type I, profound congenital sensorineural deafness, speech rarely develops, vestibular functions are abnormal. Ataxia, psychosis, and mental retardation may develop (in IA, IB, IC). In Type II, congenital hearing loss is less severe than in type I, and speech may develop, vestibular and neurological functions are normal. In Type III, there is progressive hearing loss and vestibular hypoactivity. Ataxia, psychosis, and mental retardation may develop.

Ocular Findings: Type I, retinitis pigmentosa with visual symptoms of visual loss, night blindness, and visual field loss apparent by age 10, cataract by age 40. The electroretinogram is markedly diminished or absent. Type II, visual symptoms start in the late teens. The electroretinogram is usually decreased, but a wave is recordable. Type III, visual symptoms start in the late teens.

VATER Association MIM 192350 Inheritance: sporadic. Over 250 cases reported.

General Presentation: the acronym VATER has been used to represent the major manifestations of this disorder: Vertebral anomalies, Atresia of the anus, TracheoEsophageal atresia or fistula, Radial limb defects, and Renal malformations

Ocular Findings: microphthalmia has been reported to occur in patients with hydrocephalus

von Hippel–Lindau Disease MIM *193300 Gene map locus: 3p26–p25. Inheritance: autosomal dominant. Incidence: 1:33,000.

General Description: von Hippel–Lindau (VHL) is an inherited tumor suppressor gene syndrome predisposing affected individuals to hemangioblastomas of the retina and central nervous system, renal cell carcinoma, pheochromocytoma, and renal, pancreatic, and epididymal cysts. Criteria for diagnosis in isolated cases are two or more hemangioblastomas (retinal or central nervous system) or a single hemangioblastoma in association with a visceral manifestation (pancreatic/renal/epididymal cysts, or renal carcinoma). For familial cases, the criteria for diagnosis are a single hemangioblastoma or visceral complication. The most common presenting features are retinal hemangioblastomas, followed by cerebellar hemangioblastomas, renal cell carcinoma (10%), and pheochromocytoma (5%). Retinal hemangioblastoma occur in 57%, cerebellar hemangioblastoma in 55%, spinal cord hemangioblastoma in 14%, renal cell carcinoma in 24%, and pheochromocytoma in 19%. Pancreatic tumors are usually islet cell adenomas or carcinomas. Cerebellar hemangioblastomas and renal cell carcinoma develop at an earlier age than those who develop sporadic forms of the tumor. Renal cell carcinomas are bilateral or multicentric in 50% of patients. Central nervous system hemangioblastomas are often asymptomatic and need to be detected by gadolinium-enhanced MRI. Renal cell carcinoma is the most common cause of death, and median survival is reduced to 49 years.

Ocular Findings: retinal hemangioblastomas (mean age at diagnosis is 25 years). All patients with a retinal hemangioblastoma and their first-degree relatives should be screened for VHL. Multiple retinal hemangioblastomas are diagnostic of VHL, as are single retinal hemangioblastoma and a first-degree family member with any of the manifestations of VHL. There are two types of retinal and optic nerve head hemangioblastomas: endophytic and exophytic.

TABLE 10-2. (continued).

Endophytic lesions are elevated red vascular tumors arising from the superficial retina or optic disc and growing into the vitreous. Larger peripheral tumors often have a feeding arteriole and a draining venule. Smaller tumors consist of a net of dilated capillaries and can be harder to diagnose. Visual loss results from exudative or traction retinal detachment, vitreous hemorrhage, macular edema, epiretinal membrane formation, or macular holes. Exophytic hemangioblastomas are less common and arise from the outer retinal layers, often in the peripapillary area. More posterior optic nerve hemangioblastomas may present as a progressive optic neuropathy or a chiasmal syndrome. Generally, hemangioblastomas progressively enlarge, hence the advantage of early detection and prophylactic treatment.

Waardenburg’s Syndrome, Types I, IIA, IIB, III, and IV Hirschsprung DiseasePigmentary Anomaly, Waardenburg-Ocular Albinism MIM *193500, #193510, *600193, #148820, #277580 Gene map locus: Type I, 2q35; Type IIA, 3p14.1–p12.3; Type IIB, 1p21–p13.3; Type III, 2q35; Type IV, 22q13, 20q13.2–q13.3. Inheritance; Type I, II, III have autosomal dominant transmission; Type IV has autosomal recessive transmission. Incidence: 1:20,000–40,000 live births.

General Description: Partial albinism manifested by hypopigmented ocular fundus, poliosis (white forelock), premature graying of hair, hypopigmented skin lesions (not seen in type IV), hypochromic iridis. Deafness is the most serious feature, and, if present, is usually bilateral and severe. Deafness occurs in 25% of type I cases and in 50% of type II. (Three percent of congenitally deaf children have this syndrome.) Deafness not seen in type IV. Broad and high nasal bridge with hypoplastic alae nasi, medial flare of bushy eyebrows, synophrys. Facial dysmorphism not seen in type IIB. Absent vagina, absent uterine adnexa, spina bifida, lumbosacral myelomeningocele. In type III, there are bilateral defects of the upper limbs, including hypoplasia of musculoskeletal system, carpal bone fusion, syndactyly.

Ocular Findings

Common: lateral displacement of inner canthi (in type I and III). Partial albinism manifested by hypopigmented ocular fundus, heterochromia of irides, isochromic pale blue eyes with hypoplastic iridic stroma sometimes restricted to a single segment of one eye (25%), mottled peripheral pigmentation of the retina. Often premature graying of eyelashes and eyebrows as early as age 7 years. Visual acuity is usually normal.

Less common: poor lacrimal conduction, glaucoma, unilateral ptosis, and the Marcus Gunn phenomenon (type II), anophthalmia, blepharophimosis (type III), esotropia

Walker–Warburg Syndrome Warburg Syndrome MIM *236670 Gene map locus: 9q31. Inheritance: autosomal recessive. Approximately 60 cases reported.

General Description: severe brain and eye malformations with death in the neonatal period in the majority of affected individuals. Type II lissencephaly

(100%) manifested by widespread argyria with scattered areas of macrogyria and polymicrogyria, abnormally thick cortex with absent or hypoplastic septum pellucidum and corpus callosum, cerebellar malformation (100%), Dandy–Walker malformation (53%), hydrocephalus (53%).

(continued)

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

Ocular Findings: anterior chamber malformations (91%) including cataract, corneal clouding usually secondary to Peters’ anomaly, and narrow iridocorneal angle with or without glaucoma, retinal malformations (100%) including retrolental masses caused by persistent hyperplastic primary vitreous, and retinal detachment secondary to retinal dysplasia, microphthalmia (53%), coloboma (24%), optic nerve hypoplasia, megalocornea

Weaver Syndrome MIM 277590 Inheritance: sporadic. Over 20 cases reported.

General Description: accelerated growth and maturation of prenatal onset, mild developmental delay (80%), mild hypertonia, macrocephaly (80%), flat occiput, camptodactyly, broad thumbs, thin deep-set nails, prominent fingertip pads, relatively loose skin

Ocular Findings: down-slanting palpebral fissures, hypertelorism, epicanthal folds, strabismus

Weill–Marchesani Syndrome Brachydactyly-Spherophakia Syndrome MIM *277600 Inheritance: autosomal recessive. Incidence: 1:100,000

General Description: short stature, brachycephaly, short stubby spadelike hands and feet, limited arm overhead extension, depressed nasal bridge, “pug nose,” microspherophakia, subluxated lenses, normal intelligence, occasional subvalvular fibromuscular aortic stenosis

Ocular Findings: a microspheroophakic lens (the lens diameter may be as small as 6.75 mm, and the lens may be increased by 25% in thickness), ectopia lentis (50%). The microspheroophakic lens may move into the pupillary area, causing pupillary block and glaucoma. Total dislocation into the anterior chamber is uncommon but may occur. Myopia results from spherophakia, but may be axial. The anterior chamber is usually shallow, predisposing to angleclosure glaucoma.

Werner Syndrome MIM #277700 Gene map locus: 8p12–p11.2. Inheritance: autosomal recessive. Incidence: 1:50,000–1:1,000,000

General Description: early adult appearance, with thin skin and thick fibrous subcutaneous tissue, scleroderma-like skin on face and lower legs, loss of subcutaneous fat, slim extremities with small hands and feet, beaked nose, irregular dental development, gray sparse hair, short stature, osteoporosis, atherosclerosis with calcification, muscle hypoplasia, propensity toward malignancy (10%), especially sarcoma and meningioma

Ocular Findings: cataract, retinal degeneration

Williams Syndrome Williams–Beuren Syndrome MIM *194050 Gene map locus: 7q11.2. Inheritance: autosomal dominant. Over 100 cases reported.

General Description: postnatal growth deficiency, mental retardation, friendly personality, prominent lips with open mouth, depressed nasal bridge, anteverted nares, hoarse voice, hypersensitivity to sound, mild spasticity, cardiovascular anomalies, renal anomalies

Ocular Findings

Common: medial eyebrow flare, short palpebral fissures, epicanthal folds, periorbital fullness of subcutaneous tissues, blue eyes, “stellate” pattern of the iris

TABLE 10-2. (continued).

Less common: hypertelorism, strabismus, refractive errors, tortuosity of retinal vessels

Xeroderma Pigmentosum Syndrome (Group A Through I Plus a Variant) MIM *278700, *133510, *278720, #278730, *278740, #278760, #278780, 278810, #278750 Gene map locus: Group A, 9q22.3, Group B, 2q21, Group C, 3p25, Group D,19q13.2–q13.3, Group E, 11p12–p11, Group F, 16p13.3–p13.13, Group G, 13q33, Variant type, 6p21.1–p12. Inheritance: autosomal recessive (a milder autosomal dominant form has been reported). Over 1000 cases.

General Description: the repair of UV light-induced damage to the DNA of epidermal cells is defective. The skin is normal at birth, with the first signs of the disease presenting as increased dryness and freckling on skin areas with the greatest light exposure, particularly the face. Seventy-five percent of patients show the first skin changes between 6 months and 3 years of age. Skin tumors present in the affected areas, usually before 20 years of age. Sunlight sensitivity, freckling, progressive skin atrophy with irregular pigmentation, cutaneous telangiectasia, angiomata, keratoses. Development of basal cell and squamous cell carcinoma, and less often keratocanthoma, adenocarcinoma, melanoma, neuroma, sarcoma, and angiosarcoma, squamous cell carcinoma of tongue tip, gingiva and/or palate. Slowly progressive neurological abnormalities sometimes associated with mental deterioration, microcephaly, cerebral atrophy, choreoathetosis, ataxia, spasticity, impaired hearing, abnormal speech. Occasionally, primary internal neoplasms including brain tumors, lung tumors, and leukemia. Immune abnormalities with frequent infections (33% of deaths are due to cancer and 11% due to infection). The mean age of first nonmelanoma skin cancer is 8 years. Ninety-seven percent of squamous cell and basal cell cancers occur on face, head, or neck.

Ocular Findings

Common: the most common ocular manifestation is progressive atrophy of the lower eyelid, which may lead to loss of the entire eyelid. The resulting exposure leads to inflammation, symblepharon, corneal ulceration, and corneal scarring. Conjunctival involvement begins with hyperemia with serous or mucopurulent discharge and may progress to xerosis, keratinization, and shrinkage that leads to ankyloblepharon. Neoplasms involving conjunctiva, cornea, and eyelids. The limbal zone is a common site for involvement, usually by squamous cell carcinoma. Patients often present with photophobia and conjunctivitis.

Less common: band-shaped nodular corneal dystrophy (reported in AfricanAmericans)

X-Linked Alpha-Thalassemia/Mental Retardation Syndrome ATR-X Syndrome

MIM #301040 Gene map locus: Xq13. Inheritance: X-linked recessive. Over 40 cases reported.

General Description: severe mental retardation, postnatal growth deficiency, microcephaly, low nasal bridge, small triangular nose with anteverted nares, midface hypoplasia, large “carplike” mouth frequently held open, full lips, large protruding tongue, deformed ears, tapering fingers, fifth finger clinodactyly, genital abnormalities, mild hypochromic microcytic anemia, mild form of hemoglobin H disease

Ocular Findings: telecanthus, epicanthal folds

(continued)

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

XO Syndrome Turner’s Syndrome Faulty chromosome distribution. Incidence: 1:5,000 live births.

General Description: short female, delay in motor skills, neuropsychological deficits, broad chest with wide spacing of nipples, congenital lymphedema, ovarian dysgenesis, anomalous auricles, narrow maxilla, low posterior neck hairline, short neck ( 80%), webbed posterior neck (50%), elbow and knee anomalies, narrow, hyperconvex and/or deep-set nails, excessive pigmented nevi (50%), loose skin (about the neck in infancy), kidney anomalies (60%), cardiac defects (40%), perceptive hearing impairment (50%)

Ocular Findings

Common: inner epicanthal folds (40%)

Less common: ptosis (16%), strabismus, blue sclera, cataract

XXXand XXXX Syndrome Incidence: XXX occurs in 1:1000 newborn females, XXXX reported in 40 cases.

General Description: mental deficiency, speech and behavioral problems, midfacial hypoplasia, occasional hand abnormalities, seizures

Ocular Findings: mild hypertelorism, up-slanting palpebral fissures, epicanthal folds

XXXXX Syndrome Penta X Syndrome Incidence: unknown

General Description: mental deficiency, short stature, microcephaly, low hairline, dental malocclusion, small hands with mild clinodactyly of fifth fingers, congenital heart defects (patent ductus arteriosus or ventricular septal defect)

Ocular Findings

Common: hypertelorism, epicanthal folds, mild up-slanting palpebral fissures Less common: coloboma of iris

XXXY and XXXXY Syndromes Incidence: unknown

General Description: mental deficiency, hypotonia, joint laxity, short stature, sclerotic cranial sutures, low nasal bridge, wide upturned nasal tip, low-set malformed ears, short neck, thick undersegmented sternum, limited pronation of elbow, clinodactyly of fifth finger, hypogenitalism, low dermal ridge count on fingertips

Ocular Findings

Common: wide-set eyes, up-slanting palpebral fissures, inner epicanthal folds, strabismus

Less common: down-slanting palpebral fissures, Brushfield spots, myopia

Yunis–Varon Syndrome MIM *216340 Inheritance: autosomal recessive. Thirteen reported cases.

General Description: severe developmental delay, severe failure to thrive, microcephaly, enlarged fontanels, dysplastic ears, agenesis/hypoplasia of thumbs and great toes, short tapering fingers and toes with nail hypoplasia, agenesis/hypoplasia of distal and middle phalanges of fingers and toes, absence or hypoplasia of clavicle(s). Death in the neonatal period has occurred in the majority of liveborn infants.

TABLE 10-2. (continued).

Ocular Findings

Common: sparse eyebrows and eyelashes, short up-slanting palpebral fissures Less common: sclerocornea, cataract, mild hypertelorism

Zellweger Syndrome Cerebro-Hepato-Renal Syndrome MIM #214100 Gene map locus: 2p15, 7q21–q22, 6q23–q24, Chromosome 1. Inheritance: autosomal recessive. Rare disorder.

General Description: prenatal and postnatal growth deficiency, hypotonia, seizures, gross defects of early brain development, high forehead with flat facies, hepatomegaly. Most patients die within the first year of life.

Ocular Findings

Common: up-slanting palpebral fissures, congenital cataract, pallid hypoplastic optic disc, retinal pigmentary changes, puffy eyelids, hypertelorism, Brushfield spots, epicanthal folds, cloudy cornea

Less common: glaucoma, nystagmus

References

1.Jablonski’s Multiple Congenital Abnormality/Mental Retardation website. http://www.nlm.nih.gov/mesh/jablonski/syndrome_title.html

2.Jones KL: Smith’s recognizable patterns of human malformation, 5th edn. Philadelphia: Saunders, 1997.

3.Online Mendelian Inheritance in Man (OMIM™) website. http://www.ncbi.nlm.nih.gov

4.Traboulsi EI: Genetic diseases of the eye. New York: Oxford University Press, 1998.

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