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

occiput and musculoskeletal anomalies. Ophthalmic features include hypertelorism, epicanthus, upor downward slanting of the palpebral fissures, narrow palpebral fissures, strabismus, blepharoptosis, microcornea, anterior segment dysgenesis, and a stellate pattern of the iris (see Fig. 3-5).62,66,248,254

Deletion 12p

Deletion of the short arm of chromosome 12 causes moderate to severe developmental delay with microcephaly and characteristic facial features including a long-pointed nose, micrognathia, and low-set, large ears. Other manifestations include cryptorchidism and micropenis in males. Ophthalmic features include hypertelorism, epicanthus, downward sloping of the palpebral fissures, strabismus, synophrys, sclerocornea, optic atrophy, and probably glaucoma.28,178,282,296

Ring 12

Ring formation of chromosome 12 causes growth retardation, cafe-au-lait spots, pectus excavatum, hypothyroidism, and glandular hypospadias. Ophthalmolgic features include strabismus.258

Deletion 13q

Partial monosomy for chromosome 13 caused by either deletion of part of the long arm or ring 13 results in similar phenotypes including microcephaly and trigonocephaly; facial features include a prominent bridge of the nose; small chin; large, lowset, malformed ears; and facial asymmetry (see Fig. 40-4). Other features include absent or hypoplastic thumbs, cardiac and renal malformations, anal atresia, and features of Noonan syndrome; males may have hypospadias and undescended testes. Ophthalmic findings of interstitial deletions of 13q include hypertelorism, upor downward slanting and/or narrow palpebral fissures, epicanthus, strabismus, blepharoptosis, cataract, retinoblastoma, Rieger syndrome, and colobomatous micro-

phthalmia.5,187,214,243,245,252,290,336,339,348,387

The retinoblastoma gene is located in band 14 of the long arm of chromosome 13 and has become a prototype for the study of the hereditary predisposition to cancer. The initial evidence for the location of the gene came from children who had mental

retardation, dysmorphic features, and retinoblasoma associated with a deletion in the long arm of chromosome 13332,412; approximately 6% of children with a retinoblastoma have been shown to have a detectable deletion in the same regions.36 The autosomal dominant form of the disease was later localized to the same region by the identification of linkage with esterase D,333 a red cell enzyme that had been previously mapped to the same region on the long arm of chromosome 13.334 Assay of esterase D may be a method for identification of small deletions.63 Thereafter, Benedict and colleagues23 demonstrated homozygosity for the locus (inactivation or both alleles) in tumor cell lines supporting a recessive pattern on a cellular level. The gene has been cloned,103,126,193 and risk assessment is greatly improved.48,142,381 Prenatal diagnosis may be possible for families with a germinal mutation or a balanced translocation.

Ring 13

See deletion 13q.

Deletion 14q

Partial deletion of the long arm of chromosome 14 is associated with dysmorphic facial features including a round face, hypertrichosis with thick eyebrows, a short nose with a flat root and bulbous tip; long philtrum, and micrognathia; dolichoand brachycephaly may be evident. Ophthalmic features include epicanthus, narrow palpebral fissures, strabismus, synophrys, blepharoptosis, and glaucoma.159,247,357,399,401

Ring 14

Ring formation of chromosome 14 causes growth delay and craniofacial abnormalities including microand dolicocephaly, high forehead, bulbous nasal tip, large, low-set ears, high-arched palate, micrognathia, thin upper lip, downturned corners of the mouth, and a short neck with skin folds; other manifestations include seizures, widely spaced nipples, cardiac malformations, pigmentary abnormalities including cafe-au-lait spots and viteligo, and simian creases of the hands. Ophthalmic features include hypertelorism, epicanthus, downslanting of the palpebral fissures, and alterations of the retinal pigmental

epithelium.32,158,205,314

Deletion 15q

Deletion of the q11–13 region of the long arm of chromosome 15 causes either the Angelman or Prader–Willi syndrome. Angelman syndrome is caused by deletion of the maternally derived chromosome 15, generally, bands q11.3 through q13. The syndrome is characterized by absent speech, seizures, and a puppetlike jerky gait. Prader–Willi syndrome is characterized by hypotonia, obesity with an onset in early childhood, hypogonadism, and small hands and feet; deletion of band q11.3 of the paternally derived chromosome 15 is the basis of the syndrome. In both, ocular hypopigmentation is evident.76,209,265

Ring 15

A ring formation of chromosome 15 is characterized by growth retardation, microcephaly, acromicria, and micrognathia; other features include cardiac, renal, and skeletal malformations; cafe au lait spots; and gonadal hypoplasia. Ophthalmic features include hypertelorism, strabismus, nystagmus, and retinal depigmentation.38,109,192,397

Deletion 16q

Deletion of the long arm of chromosome 16 causes growth retardation, hypotonia, and craniofacial malformations including a high forehead, large anterior fontanel, prominent metopic suture, diastasis of the cranial sutures, low-set, dysplastic ears, micrognathia, and a short neck. Additional features include intestinal, cardiac, skeletal, and renal malformations. Band 16q21 is believed to be responsible for the distinctive aspects of the syndrome. Ophthalmolgic features include narrow and upand downward slanting of the palpebral fissures, hypertelorism, strabismus, and epicanthus.105,115,225,292

Deletion 17p

An interstitial deletion of the short arm of chromosome 17 in the p11 band causes mental retardation with hypotonia, seizures, and craniofacial anomalies consisting of microand brachycephaly, prominent forehead, a broad face with a flattened midfacial region, broad nasal bridge, malformed and malpositioned ears, prominent jaw, and delayed dentition. Additional

features include digital anomalies such as broad short hands, hearing loss, deep voice, and cardiac and genital anomalies. Ophthalmic features include upor downward slanting of the palpebral fissures, strabismus, Brushfield spots of the iris, synophrys, and colobomatous microphthalmia.207,260,328,339

A deletion of the p13 region of the short arm of chromosome 17, Miller–Dieker syndrome, is associated with lissencephaly (smooth brain) and agyri or pachygyria. Additional malformations of the brain may be evident. Affected individuals have severe mental retardation with seizures and hypotonia. Ophthalmic manifestations include hypertelorism, upslanting and/or narrowing of the palpebral fissures, and epicanthus.140

Ring 17

Ring 17 is associated with mental retardation, microcephaly, and short stature. Features of neurofibromatosis I may be evident. Flecked retina with subretinal drusen-like deposits has been reported.49

Deletion 18p

The physical findings associated with the deletion (total or partial) of the short arm of chromosome 18 are broad. In the mildest form, affected individuals have microcephaly, mild mental retardation, short stature, webbed neck, and immunoglobulin abnormalities.138 In the most severe form, median facial dysplasia with cebocephaly and/or incomplete morphogenesis of the brain may occur, with digital anomalies such as short fingers, high-set thumb(s), and syndactyly. Cardiac, renal, and gastrointestinal malformations are uncommon but may be evident. The ophthalmic features consistently include hypertelorism, epicanthus, blepharoptosis, and strabismus. Cataracts, retinal dysplasia, colobomatous microphthalmia, and synophthalmia/cyclopia have been reported.113,156,188,208,311,395

Deletion 18q

Partial deletion of the long arm of chromosome 18 produces a syndrome marked by mental and growth retardation with hypotonia. The facies is striking with microcephaly, midface hypoplasia, a carplike mouth with downward slanting margins, and a prominent antihelix and/or antitragus of the ears with a

narrow or atretic canal and hearing loss. Cardiac and genitourinary malformations are common. The fingers taper markedly with a high frequency of whorl patterns, and simian creases may be evident. Toes have abnormal placement with the third toe placed above the second and fourth. Dimples may be evident on knuckles, knees, elbows, and shoulders. Ophthalmic abnormalities include epicanthus, hypertelorism, downward slanting of the palpebral fissures, nystagmus, strabismus, corneal abnormalities, cataracts, blue sclerae, dysplastic or atrophic optic nerve heads, and colobomatous

microphthalmia.60,70,92,208,239,309,354,390

Ring 18

The physical findings of ring formation of chromosome 18 overlaps both the short arm and long arm deletion syndromes, although the manifestations are usually less severe than the monosomy 18 syndromes (see earlier). Ophthalmic features include epicanthus, hypertelorism, strabismus, nystagmus, blepharoptosis, colobomatous microphthalmia, and cyclopia.78,156,190,208 Yanoff et al. histopathologically studied the eyes in the case of cebocephaly with a ring 18, and bilateral microphthalmia with cyst, intrascleral cartilage, intrachoroidal smooth muscle, and other anomalies were evident; however, no recognizable components of the optic system could be identified.400

Deletion 19p

Deletion of the short arm of chromosome 19 is associated with significant mental retardation and microcephaly. Facial features include low-set ears, flat nose, micrognathia, high-arched palate, and downturned corners of the mouth. Ophthalmic features hypertelorism and persistent hyperplastic primary vitreous.162

Deletion 20p

Deletion of the short arm of chromosome 20 causes growth delay and characteristisc facial features including a low and flat nasal bridge, maxillary hypoplasia, long philtrum, thin upper lip, small mandible, low-set ears, and a high-arched palate. Additional manifestations include upper airway obstruction, digital anomalies, and cardiac malformations. Ophthalmic features

include epicanthus, hypertelorism, downward slanting of the palpebral fissures, strabismus, colobomata of the irides, and the anterior segment features of the Rieger or Alagille syndromes.10,325

Ring 21

The clinical features of ring 21 are similar to monosomy 21. Visceral anomalies are relatively consistent features. Reported ophthalmic manifestations include upor downward slanting of the palpebral fissures and dysgenesis of the anterior segment similar to that of Peters’ anomaly.65,94,128,151,155,229

Deletion 22q

The velo-cardio-facial (DiGeorge) syndrome has been associated with a deletion of the long arm of chromosome 22 in the region of band 11. The DiGeorge syndrome is characterized by aplasia of the thymus and parathyroids; the disorder may be referred to as the third and fourth pharyngeal pouch syndrome. Reported ophthalmic features include hypertelorism and upor downslanting of the palpebral fissures.41,71,175,317

Ring 22

Ring 22 causes mental retardation with microcephaly and craniofacial features including bulbous nose, high-arched palate, and large ears. Additional manifestations include renal anomalies such as polycystic kidneys and cardiac malformations. Ophthalmic features include epicanthus downslanting of the palpebral fissures, strabismus, synophrys, and proptosis.117,125,161,204

DUPLICATION SYNDROMES

Duplication 1q

Partial trisomy of the long arm of chromosome 1 is characterized by facial dysmorphism with deep-set eyes, a broad nasal bridge, retrognathia, and posteriorly rotated ears; mental retardation and seizures may be evident. Ophthalmic features include narrow horizontal palpebral fissures, synophrys, and colobomatous microphthalmia.49,256,257,269,346

receding forehead, prominent nasal bridge, low-set and/or dysplastic ears, a long or short philtrum, and a carp-shaped mouth or macrostomia. Additional features include digital anomalies and cardiac disease. Ophthalmic features include epicanthus, hypertelorism, and strabismus.189

Duplication 6p

Trisomy of the short arm of chromosome 6 is characterized by preand postnatal growth retardation. Affected individuals have a characteristic craniofacial dysmorphism with dolichocephaly, a high forehead with a high and broad nasal bridge, bulbous nose with hyperplastic nares, short philtrum, small mouth with thin lips, and micrognathia; choanal atresia, camptodactyly, syndactyly, and genitourinary malformations may be evident. Ophthalmic features include hypertelorism, strabismus, long lashes, blepharophimosis, blepharoptosis, optic atrophy, and microphthalmia.112,329

Duplication 6q

Trisomy of the long arm of chromosome 6 is characterized by minor dysmorphic features in infancy with development of turricephaly and a prominent forehead with or without microcephaly in childhood. The neck is broad, short, and webbed. The nipples are wide spaced with deformities of the chest and spine; joint contractures are common. Hypospadius and cryptorchidism may also be evident. Ophthalmic features include downward slanting of the palpebral fissures, epicanthus, hypertelorism, blepharoptosis, strabismus, hypoplastic supraorbital ridges, and thin, arched eyebrows.50,55,350,355

Duplication 7p

Duplication of the short arm of chromosome 7 causes dolichocephaly or microbrachycephaly, gaping fontanels, and wide sagittal and metopic sutures, large and low-set ears, and small mouth with downturned corners, micrognathia; other features include choanal atresia/stenosis, skeletal anomalies including hyperextensible joints, camptodactyly and rocker-bottom feet, joint contractures, and cardiac, central nervous system, and genitourinary malformations. Ophthalmic features include hyper-

telorism, epicanthus, upor downward slanting of the palpebral fissures, and microphthalmia.24,231

Duplication 7q

Partial trisomy of the long arm of chromosome 7 in bands 2 to 3 causes preand postnatal growth retardation, delayed skeletal maturation including closure of the fontanelles, hypotonia, seizures, central nervous system malformations including hydrocephalus, hypoplasia of the corpus callosum, cerebral and cerebellar atrophy, and hypoplasia of the cerebellar vermis. Facial features include frontal bossing, depression of the nasal bridge, upturned nares, long philtrum, cleft palate, small mandible, dysplastic ears, and short neck and skeletal anomalies include scoliosis, hemivertebrae, absent ribs, joint laxity or stiffness, hip dislocation, camptodactyly, short midhands with a single transverse palmar crease, and long fingers and toes. Ophthalmologic features include hypertelorism, downward slanting and/or narrow palpebral fissures, epicanthus, strabismus, absent lateral rectus muscles, “prominent eyes,” long lashes, optic nerve hypoplasia, and colobomatous microphthalmia/anoph-

thalmia.95,139,169,174,295,321,370,371

Duplication 8p

Trisomy of the short arm of chromosome 8 is characterized by a high, prominent forehead, an everted lower lip, a poorly defined philtrum, macrostomia with gingival hypertrophy, a low nasal bridge and anteverted nostrils, and large, soft ears with excess folds. Hypotonia is common. Other features include flexion contractures and clubfeet; cardiac, central nervous system, and renal malformations; and spina bifida. Ophthalmic features include hypertelorism and upward slanting of the palpebral fissures.56,111,217

Duplication 8q

Duplication of the long arm of chromosome 8 causes growth retardation and craniofacial features including a prominent and short forehead, a broad and flat nose with a short septum, dysplastic ears, and a short upper lip. Additional manifestations include a funnel chest, hypertrichosis, and skeletal anomalies including coxa valga and brachyand clinodactyly. Ophthalmic