10 Ocular Manifestations of Inherited Diseases Maya Eibschitz-Tsimhoni ecognizing an ocular abnormality may be the first step in Ridentifying an inherited condition or syndrome. Identifying an inherited condition may corroborate a presumptive diagno- sis, guide subsequent management, provide valuable prognostic information for the patient, and determine if genetic counseling is needed. Syndromes with prominent ocular findings are listed in Table 10-1, along with their alternative names. By no means is this a complete listing. Two-hundred and thirty-five of approxi- mately 1900 syndromes associated with ocular or periocular manifestations (both inherited and noninherited) identified in the medical literature were chosen for this chapter. These syn- dromes were selected on the basis of their frequency, the char- acteristic or unique systemic or ocular findings present, as well as their recognition within the medical literature. The boldfaced terms are discussed further in Table 10-2. Table 10-2 provides a brief overview of the common ocular and systemic findings for these syndromes. The table is organ- ized alphabetically; the boldface name of a syndrome is followed by a common alternative name when appropriate. Next, the Online Mendelian Inheritance in Man (OMIM™) index num- ber is listed. By accessing the OMIM™ website maintained by the National Center for Biotechnology Information at http://www.ncbi.nlm.nih.gov, the reader can supplement the material in the chapter with the latest research available on that syndrome. A MIM number without a prefix means that the mode of inheritance has not been proven. The prefix (*) in front of a MIM number means that the phenotype determined by the gene at a given locus is separate from those represented by other 526 chapter 10: ocular manifestations of inherited diseases 527 asterisked entries and that the mode of inheritance of the phe- notype has been proven. The prefix (#) indicates that the same phenotype can be caused by mutation in any of two or more genes. After the MIM number, the affected gene location is indi- cated, when known, followed by the mode of inheritance and the incidence or number of cases reported. A general description of the syndrome featuring systemic manifestations is then provided, followed by pertinent ocular findings. Ocular findings are separated between “common” and “less common.” Under “less common” abnormalities, reported sporadic abnormalities are listed that are not necessarily related to the disease. Findings that are in quotation marks are listed as they were originally described (often not in ophthalmologic nomenclature). A glossary of terms associated with inherited diseases precedes the tables. Jablonski’s Multiple Congenital Abnormality/Mental Retar- dation website at http://www.nlm.nih.gov/mesh/jablonski/ syndrome_title.html is another fine resource for additional information. 528 handbook of pediatric eye and systemic disease Glossary The following terms are associated with inherited diseases. Acanthocytosis a rare condition in which the majority of erythrocytes are acanthocytes; a thorny or peculiarly spiny erythrocyte characterized by multiple spiny cytoplasmic projections. Commonly seen in abetaliproproteinemia. Acrocephaly see oxycephaly. Anencephaly congenital absence of most of the brain and spinal cord. Aplasia cutis congenita congenital absence or deficiency of a localized area of skin, with the base of the defect covered by a thin translucent membrane. Arachnodactyly a hereditary condition characterized by exces- sive length of the fingers and toes. Argyria permanent dark discoloration of skin caused by overuse of medicinal silver preparations. Arhinencephaly an absence or rudimentary state of the rhino- encephalon, or olfactory lobe of the brain, on one or both sides, with a corresponding lack of development of the external olfactory organs. Arthrogryposis the permanent fixation of a joint in a con- tracted position. A congenital disorder marked by generalized stiffness of the joints, often accompanied by muscle and nerve degeneration, which results in severely impaired mobility of the limbs. Bathocephaly craniosynostosis involving the posterior sagittal suture. Brachycephaly having a short, broad head with a cephalic index over 80. Brachydactyly having abnormally short fingers or toes. Camptodactyly permanent flexion of one or more finger joints. Clinodactyly a deformity of the hand marked by deviation or deflection of the fingers. Craniosynostosis premature fusion of the sutures of the skull. Cutis marorata marble-like mottling of the skin on exposure to cold, common in children and some adults. Dandy–Walker Syndrome hydrocephalus in infants associated with atresia of the foramen of Magendie. Ectrodactyly congenital complete or partial absence of one or more digits. chapter 10: ocular manifestations of inherited diseases 529 Holoprosencephaly failure of the forebrain to divide into hemi- spheres or lobes. Hypodactyly small fingers and/or toes. Klippel–Feil Syndrome congenital fusion of the cervical verte- brae resulting in a short and relatively immobile neck. Metaphysis the transitional zone at which the diaphysis and epiphysis of a bone come together. Micrognathia abnormal smallness of jaw. Omphalocele protrusion of abdominal contents through an opening at the navel, occurring especially as a congenital defect. Oxycephaly a congenital abnormality of the skull in which the top of the head assumes a conical or pointed shape. Also called: acrocephaly, turricephaly. Polydactyly the condition of having more than the normal number of toes or fingers. Prognathism a jaw that projects forward to a marked degree. Scaphocephaly a congenital deformity of the skull in which the vault is narrow, elongated, and boat-shaped because of pre- mature ossification of the sagittal suture. Symphalangism ankylosis of the joints of one or more digits. Syndactyly a congenital anomaly in humans characterized by two or more fused fingers or toes. Synostosis the fusion of normally separate skeletal bones. Tapetoretinal of, relating to, or involving both tapetum and retina. Tapetum a membranous layer or region, especially the irides- cent membrane of the choroid. Trigonocephaly congenital deformity in which the head is somewhat triangular and flat. Turricephaly see oxycephaly. 530 handbook of pediatric eye and systemic disease TABLE 10-1. Syndromes with Prominent Ocular Findings and Their Alternative Names. 2qϪ Syndrome—see Deletion 2q Syndrome (2q33.3–q34) 3pϪ Syndrome—see Deletion 3p Syndrome 3qϩ Syndrome—see Duplication 3q Syndrome 4pϪ Syndrome—see Deletion 4p Syndrome 4qϪ Syndrome—see Deletion 4q Syndrome 5pϪ Syndrome—see Deletion 5p Syndrome 9pϪ Syndrome—see Deletion 9p Syndrome 10qϩ Syndrome—see Duplication 10q Syndrome 11pϪ Syndrome—see Deletion 11p Syndrome 13qϪ Syndrome—see Deletion 13q Syndrome 15qϪ Syndrome—see Deletion 15q Syndrome 18pϪ Syndrome—see Deletion 18p Syndrome 18qϪ Syndrome—see Deletion 18q Syndrome A Aarskog Syndrome Aase Syndrome Aase–Smith Syndrome Abetalipoproteinemia Ablepharon–Macrostomia Syndrome Abruzzo–Erickson Syndrome Acrocallosal Syndrome, Schinzel Type Acrocephalopolydactylous Dysplasia Acrocephalopolysyndactyly Type 2—see Carpenter Syndrome Acrocephalopolysyndactyly Type 4—see Goodman Syndrome Acrocephaloysyndactyly Type 1—see Apert Syndrome Acrocephaloysyndactyly Type 5—see Pfeiffer Syndrome Acrodysostosis Acrofacial Dysostosis 1, Nager Type—see Nager Syndrome Acrofacial Dysplasia—see Geleophysic Dysplasia Acro-Fronto-Facio-Nasal Dysostosis Syndrome Acromegaloid Facial Appearance Syndrome Acromegaloid Phenotype–Cutis Verticis Gyrata–Corneal Leukoma Acromesomelic Dwarfism—see Acromesomelic Dysplasia, Maroteaux–Martinelli–Campailla Type Acromesomelic Dysplasia, Maroteaux–Martinelli–Campailla Type Acromicric Dysplasia Acro-Osteolysis Syndrome—see Hajdu–Cheney Syndrome Acro-Reno-Ocular Syndrome Adams–Oliver Syndrome AEC Syndrome—see Hay–Wells Syndrome of Ectodermal Dysplasia Aglossia-Adactyly Syndrome—see Oromandibular-Limb Hypogenesis Spectrum Aicardi’s Syndrome Alagille Syndrome—see Arteriohepatic Dysplasia Albright Hereditary Osteodystrophy Angelman Syndrome—see Deletion 15q (deletion of maternal allele) Angio-Osteohypertrophy Syndrome—see Klippel–Trenaunay–Weber Syndrome (KTW Syndrome) Ankyloblepharon-Ectodermal Dysplasia-Clefting Syndrome—see Hay–Wells Syndrome of Ectodermal Dysplasia chapter 10: ocular manifestations of inherited diseases 531 TABLE 10-1. (continued). Anophthalmia with Limb Anomalies Antley–Bixler Syndrome Apert Syndrome Arteriohepatic Dysplasia Arthro-Ophthalmopathy, Hereditary, Progressive, Stickler Type (AOM), Membranous Vitreous Type—see Stickler Syndrome Asphyxiating Thoracic Dystrophy—see Jeune Thoracic Dystrophy Ataxia-Telangiectasia Syndrome ATR-X Syndrome—see X-Linked Alpha-Thalassemia/Mental Retardation Syndrome Axenfeld–Rieger Anomaly with Atrial Septal Defect and Sensorineural Hearing Loss Axenfeld–Rieger Anomaly with Partially Absent Eye Muscles, Distinctive Face, Hydrocephaly, and Skeletal Abnormalities B Baller–Gerold Syndrome Bannayan Syndrome—see Bannayan–Riley–Ruvalcaba Syndrome Bannayan–Riley–Ruvalcaba Syndrome Bardet–Biedl Syndrome Type I–VI Bassen–Kornzweig disease—see Abetalipoproteinemia Beals’ Syndrome Beckwith–Wiedemann Syndrome Berardinelli–Lipodystrophy Syndrome Berardinelli–Seip Congenital Lipodystrophy Syndrome—see Berardinelli–Lipodystrophy Syndrome Berman’s Syndrome—see Sialolipidosis Syndrome Bernheimer–Seiteberger disease—see Gangliosidosis Syndrome (GM2), Type III Beta-Glucuronidase Deficiency—see