Genetic diseases of the eye, edited by Elias I Traboulsi
GENETIC DISEASES OF THE EYE
This multiauthor text is the 36th Oxford Monograph on Medical Genetics. It is edited by Dr. Traboulsi but there are two consulting editors, Dr. Irene Maumenee and Dr. Linn Murphree. All three editors are well known for their research and publications in ophthalmic genetics.
The book is divided into seven sections and has a total of 42 chapters. The first section deals with developmental abnormalities and includes an excellent introductory chapter on the embryology of the eye and the role of developmental genes. This chapter discusses the expression and functions of PAX6, PAX2, CHX10, BMP7, and γE-Crystallin and their mouse homologues. The chapter is well illustrated, but there are some labeling errors in the figures describing the formation of the optic cup. The next chapter, on malformations of the ocular adnexae, includes good summaries on coloboma of the eyelid, cryptophthalmos, and epibulbar choristomas, including common malformation syndromes associated with these anomalies. Both the ophthalmologist and the clinical morphologist will find the chapters on colobomatous microphthalmia, anophthalmia, and associated malformations, malformations of the anterior segment of the eye, and congenital anomalies of the optic nerve head in this section very helpful and a good reference source. The chapter on colobomatous microphthalmia contains an excellent table that offers a practical classification of this abnormality. However this chapter contains a few errors and omissions. An example of the former is that Jean Aicardi, who first described Aicardi syndrome, is a French paediatric neurologist and not a French radiologist. An example of the latter is the omission of any information about the gene for Sjögren-Larsson syndrome, fatty aldehyde dehydrogenase, which was identified in 1996.
The chapter on aniridia provides a review of this ocular malformation and provides information on the other ocular malformations that can be caused by mutations in the PAX6 gene such as Peters' anomaly and other anterior segment malformations. This chapter also discusses genetic counseling when both partners have aniridia. The chapter on congenital abnormalities of the retinal pigment epithelium is excellent. It allows the reader to clearly differentiate between focal and diffuse abnormalities of the retinal pigment epithelium. The former include congenital hypertrophy of the retinal pigment epithelium and congenital grouped pigmentation of the retinal pigment epithelium, neither of which is associated with any extraocular abnormalities, whereas the latter include polymorphic pigmented ocular fundus lesions, which can be seen in familial adenomatous polyposis. The last chapter in Section I is a useful review of the inheritance of refractive errors. This chapter also includes a table listing some of the syndromes associated with refractive errors such as astigmatism in Crouzon and other craniosynostosis syndromes.
Section II deals with hereditary disorders of the anterior segment of the eye and includes chapters on congenital glaucoma, open-angle glaucoma, cataracts, corneal dystrophies, and keratoconus. Every chapter provides an up-to-date review of the clinical findings and genetics of each condition. The chapter on congenital glaucoma provides a useful classification of primary and secondary childhood glaucoma and a very useful table of the causes of cloudy cornea in children. The chapter on cataracts is well illustrated with colour photographs of the different types of congenital cataracts and cataracts seen in systemic disorders such as galactosaemia, Lowe syndrome, Wilson disease, etc. There is also a good discussion of single-gene multisystemic disorders and chromosomal abnormalities that can be associated with cataracts. The chapter on corneal dystrophies is also well illustrated with superb colour photographs showing the corneal appearances on direct illumination and on retroillumination in several different types of corneal dystrophy.
Section III covers retinal dystrophies and degeneration and starts with an excellent chapter on retinal function testing and genetic disease. The chapter on retinitis pigmentosa (RP) provides a good review of heterogeneity of this disorder and the pathogenesis of photoreceptor dystrophies. However, it provides very little information about genetic counseling of isolated cases of RP. For example, no information is provided about whether the mother of an isolated male case of RP should have only fundus examination or fundus examination and EOG/ERG and what the residual risks are of X-linked RP in this situation if the results of the mother's tests are normal. Juvenile retinoschisis (JR) and North Carolina macular dystrophy are covered in separate chapters. The chapter on JR reviews the clinical and ERG aspects of this condition, including the Mizuo-Nakamura phenomenon, and also provides a good differential diagnosis of this disorder. This chapter also makes it clear that female carriers of this X-linked recessive disorder cannot be identified clinically by ophthalmologic examination, visual function testing, or ERG.
This section also includes a separate chapter on cone dystrophies that discusses rod monochromacy (achromatopsia), Mendelian forms of pure cone and cone-rod degenerations, and the various loci that have been mapped for these disorders. This chapter also discusses the cone degeneration seen in some syndromes such as Bardet-Biedl syndrome (BBS). The ocular findings of BBS are also discussed in the chapter on pigmentary retinopathy and systemic disease in Section V of the book. There is also a chapter on Leber congenital amaurosis, Stargardt disease, and pattern dystrophies. The clinical findings, classification, and genetic heterogeneity of Leber congenital amaurosis are nicely reviewed. Best macular dystrophy is also reviewed in this chapter. The heterogeneity of Stargardt disease is discussed including the identification of mutations in the ABCR gene in a recessive form of this disorder. There are good colour fundus photographs of Stargardt disease as well as the different stages of Best disease, and the heterogeneity of the latter condition is also discussed. This section also contains excellent chapters on congenital stationary night blindness, choroideraemia, age-related maculopathy, hereditary vitreoretinopathies, and optic atrophy. There is some repetition in the chapter on hereditary vitreoretinopathies that includes further discussion of congenital X-linked retinoschisis. This chapter also includes a good discussion of the ocular findings in Stickler syndrome, but this fails to mention that mutations in the COL11A1 gene can also cause Stickler syndrome with vitreoretinopathy.
Section IV of this book discusses disorders of ocular motility. It includes chapters on the Duane, Möbius, and fibrosis syndromes, congenital nystagmus, and blepharoptosis. The chapter on Duane syndrome discusses the genetics of isolated Duane syndrome as well as syndromic forms of Duane anomaly such as Okihiro syndrome, Acro-renal-ocular syndrome, Wildervanck syndrome, etc. The discussion on the syndromic forms of Duane anomaly rightly questions whether Duane anomaly is a component of Holt-Oram syndrome and also discusses the phenotypic overlap of Okihiro and acro-renal-ocular syndromes. Chromosomal abnormalities associated with Duane anomaly are also discussed. Möbius syndrome and its genetics is also very well reviewed. The chapter on blepharoptosis provides a good review of the ocular aspects of the blepharophimosis-ptosis-epicanthus inversus syndrome.
Section V discusses the ocular manifestations of inherited systemic diseases. It includes chapters on ocular manifestations of chromosomal abnormalities, subluxation of the crystalline lens and associated systemic disease, and pigmentary retinopathy and systemic disease. There is also a superb chapter on peroxisomal disorders, which I thought was one of the best-written chapters on this difficult subject. This section also contains chapters on albinism, mitochondrial disorders, the phakomatoses, and syndromes with craniofacial anomalies. The chapter on the phakomatoses is excellent and well illustrated with a table listing the differential diagnosis of Lisch nodules and a table listing the primary, secondary, and tertiary diagnostic criteria of tuberous sclerosis complex. The chapter on syndromes with craniofacial anomalies provides a very good review of the manifestations and molecular genetics of the craniosynostosis syndromes. The final chapter of this section is on Norrie disease. It provides a short review of this disorder and mentions that some families with X-linked exudative vitreoretinopathy and X-linked primary retinal dysplasia also have been found to have mutations in the Norrie disease gene. There is no mention of the possible association of advanced stages of retinopathy of prematurity with missense mutations in the Norrie disease gene.
Section VI covers tumours and includes chapters on uveal melanoma and retinoblastoma. The final section of this book is on management. This section has a chapter on vision rehabilitation of the patient with genetic eye disease and a final chapter that lists the organisations serving the visually impaired and individuals with genetic diseases. The book concludes with an appendix, a very useful gene map of heritable ocular disorders.
This is quite simply a superb book and obviously a labour of love. It is well written and beautifully illustrated, and I have no doubt that it will go on to become a classic in its field. Because of the nature of its subject it will need frequent revision as more and more genes for ocular disorders are identified and the pathogenesis of these disorders is better understood. I have found this book to be an excellent resource when I have been called on to give genetic advice to patients with ocular disorders. It is also an excellent reference for the ocular involvement in syndromes. Who should buy this book? I think that every clinical genetics department should have a copy of this book, as should every department of ophthalmology and paediatrics. Every clinical geneticist in training should read this book and every practising clinical geneticist who sees patients or families with heritable ocular disorders or with an interest in clinical dysmorphology should have this book or at least have access to it. Although expensive it is definitely worth every penny spent.
