DOCSLIB.ORG

Abnormal Foveal Morphology in Ocular Albinism Imaged with Spectral-Domain Optical Coherence Tomography

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Abnormal Foveal Morphology in Ocular Albinism Imaged with Spectral-Domain Optical Coherence Tomography CLINICAL SCIENCES Abnormal Foveal Morphology in Ocular Albinism Imaged With Spectral-Domain Optical Coherence Tomography Gabriel T. Chong, MD; Sina Farsiu, PhD; Sharon F. Freedman, MD; Neeru Sarin, MBBS; Anjum F. Koreishi, BS; Joseph A. Izatt, PhD; Cynthia A. Toth, MD Objectives: To evaluate the spectrum of foveal archi- Pudlak syndrome: persistence of an abnormal, highly tecture in pediatric albinism and to assess the utility of reflective band across the fovea, multiple inner retinal spectral-domain optical coherence tomography (OCT) layers normally absent at the center of the fovea, and loss in ocular imaging of children with nystagmus. of the normally thickened photoreceptor nuclear layer at the fovea when compared with that in control sub- Methods: Spectral-domain OCT imaging was per- jects. The optic nerve was elevated in multiple eyes formed on study subjects in 3 groups: subjects with of subjects with OA or suspected OA and the subject ocular albinism (OA) or suspected OA with foveal hypo- with oculocutaneous albinism and Hermansky-Pudlak plasia, with nystagmus, and with or without iris trans- syndrome. illumination; a subject with oculocutaneous albinism and Hermansky-Pudlak syndrome; and control subjects. Dense Conclusions: A spectrum of foveal morphological ab- volumetric scans of each fovea were captured using stan- normalities is seen in subjects with OA or suspected OA, dard and handheld spectral-domain OCT devices. Im- which in some cases contrasted with previous studies ages were postprocessed and scored for the presence and using time-domain OCT. These OCT findings clarify configuration of each retinal layer across the fovea. the morphology of foveal hypoplasia seen clinically. Results: High-quality spectral-domain OCT images ob- This imaging modality may be useful in evaluating tained from each subject revealed a range of abnormali- children. ties in subjects with OA or suspected OA and the sub- ject with oculocutaneous albinism and Hermansky- Arch Ophthalmol. 2009;127(1):37-44 CULAR ALBINISM (OA) IS graded, while at the same time with fo- a genetic disorder of veal hypoplasia, central vision should be melanin production that diminished owing to widely spaced cen- occurs with a frequency tral cones.4,8,9 of about 1 in 50 000 per- The nystagmus seen in albinism usu- Osons in the United States.1 In contrast to ally manifests by age 2 or 3 months and oculocutaneous albinism (OCA) involv- often lessens with age and near vision as ing skin, hair, and eyes, OA is limited to a result of convergence.10 Nystagmus is the eyes.2 Ocular albinism type 1 is an in- probably due to the foveal hypoplasia (ab- herited X-linked disease causing ocular sent foveal pit on light microscopy) and clinical features that may include nystag- the aberrant visual pathways seen in pa- mus, decreased visual acuity, hypopig- tients with albinism.3,10 In addition, astig- mentation of the retina, foveal hypopla- matism and other refractive errors are com- sia, translucency of the iris, macular mon and could lead to some degree of transparency, photophobia, and abnor- amblyopia and low visual acuity.4 Owing mal neuronal wiring (abnormal decussa- to misrouting of the optic pathways, pa- Author Affiliations: tion of nerve fibers at the chiasm).3-5 The tients with OA are at high risk for strabis- Departments of Ophthalmology decreased visual acuity varies, and re- mus and loss of stereovision.4 (Drs Chong, Farsiu, Freedman, ports suggest that visual acuity is re- The genetics involved in OCA type 1 Sarin, Izatt, and Toth and duced to 20/25 to 20/200.6-8 It is possible (OCA1) focus on mutations in the tyrosi- Mr Koreishi) and Biomedical 2 Engineering (Drs Izatt and that with decreased pigmentation, light en- nase gene. Those individuals who lack Toth), Duke University, tering the eye is more prone to scattering pigment owing to complete inactivity of Durham, North Carolina. and the resulting retinal image is de- the tyrosinase gene have OCA1A, whereas (REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 1), JAN 2009 WWW.ARCHOPHTHALMOL.COM 37 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 those with mutations in the tyrosinase gene that allow ing other ophthalmic imaging studies performed at Duke Uni- residual enzyme activity have OCA1B. Individuals have versity Eye Center. Study subjects were examined by a pedi- OCA2, OCA3, and OCA4 when there is a mutation in atric ophthalmologist (S.F.F.). Clinical examination included the P-gene on chromosome 15q, the tyrosine-related pro- best-corrected visual acuity, presence and type of manifest nys- tein 1 gene, or the membrane-associated transporter gene, tagmus, skin color, hair color, iris color, and presence or ab- sence of transillumination defects (assessed in a darkened room respectively.2 Hermansky-Pudlak syndrome (HPS), caused with the subject sitting at a slitlamp biomicroscope unless the by mutations in 1 of 7 HPS genes, and Che´diak-Higashi child could not sit at the table-mounted slitlamp biomicro- syndrome, caused by a mutation in the lysosomal- scope, in which case a portable slitlamp was used). Fundus ex- trafficking regulator gene, are multisystemic disorders as- amination was performed with an indirect ophthalmoscope and sociated with OCA.3 Except for OCA1A, individuals with either a 20-diopter (D) or 28-D condensing lens. Skin biopsy the conditions described earlier may have some pig- and/or genetic testing were not performed in subjects with OA ment in the skin, hair, and irides. or suspected OA or control subjects in this study. The subject Optical coherence tomography (OCT) is the optical with OCA and HPS was diagnosed previously by genetic test- analogue to ultrasonography and measures the echo time ing. Subjects with foveal hypoplasia (determined clinically via delay and magnitude of reflected or backscattered light visualization with indirect ophthalmoscopy using a 20-D lens, using low-coherence interferometry.11 Cross-sectional im- looking for absence of the foveal pit), with nystagmus on clini- ages are obtained by measuring the backscattered light cal examination, and with or without iris transillumination de- fects were included in the group with OA or suspected OA. Con- while scanning across multiple sites in a transverse fash- trol subjects were white, were aged between 5 and 11 years, ion. The data obtained are displayed as false-color or gray- had normal skin and hair pigmentation, had 20/20 visual acu- scale images. ity in each eye, and lacked nystagmus. The subject with OCA A conventional time-domain (TD) OCT system (Stra- had a diagnosis of HPS. This subject was chosen as a positive tus OCT; Carl Zeiss Meditec, Dublin, California) can pro- control to verify the findings of OCA when compared with the vide 8- to 10-µm axial resolution and 512 axial scans in subjects with suspected OA who did not clearly have albi- 1.3 seconds.11 Clinical limitations of the relatively slow nism. As the subject with OCA and HPS was already sched- standard TD-OCT are partially due to the subject’s eye uled to undergo anesthesia for strabismus surgery, imaging un- motion, which can lead to image artifacts. Such artifacts der anesthesia allowed for the entire posterior pole to be imaged may be reduced by exploiting cross-correlation algo- under controlled conditions to ensure that the area where the fovea might be located would not be inadvertently bypassed rithms that automatically align adjacent axial scans and 11 during SD-OCT imaging. with eye-tracking protocols. Ultrahigh-resolution OCT The retinas of both eyes of the study subjects were then imaging with axial resolutions of 2 to 3 µm has been used scanned using SD-OCT, and the eye with the best images, either to demonstrate retinal morphology with improved de- right or left, was used for analysis. The subject with known OCA tail. Unfortunately, ultrahigh-resolution OCT is even also had SD-OCT imaging of each retina performed while su- slower than the TD systems, where scanning speeds are pine during scheduled anesthesia for strabismus surgery, and typically 150 to 250 axial scans per second.11 Thus, im- SD-OCT was performed using a portable, handheld, noncon- age artifacts due to eye motion are more severe and cov- tact SD-OCT device (Bioptigen Inc, Research Triangle Park, erage is more restricted.11 North Carolina). To overcome such limitations, ophthalmic imaging re- We used an SD-OCT system developed by one of us (J.A.I.) with operating software provided by Bioptigen Inc that was re- search is now progressively relying on the novel (Fou- 11-13 fined for imaging patients with OA (in collaboration with rier) spectral-domain (SD) OCT systems. The SD- C.A.T.). The SD-OCT light source is a superluminescent di- OCT systems have a higher speed and a sensitivity ode (Superlum Diodes, Ltd, Carrigtwohill, County Cork, Ire- advantage over the conventional OCT systems (50 times land) with a central wavelength of 840 nm and a bandwidth of faster than standard TD-OCT and 100 times faster than 49 nm, yielding a theoretical axial resolution of 6.3 µm in air ultrahigh-resolution OCT imaging systems).11 Owing to and 4.6 µm in tissue. The lateral resolution of each A-scan was the increase in speed, a single cross-sectional scan of 1000 approximately 15 to 20 µm. The power incident on the study A-scans can be captured, processed, and displayed in about subject’s cornea was roughly 500 µW, which is well below the American National Standards Institute’s extended exposure limit 60 milliseconds. This reduces target motion artifacts, re- 14 sulting in a more stable captured image. This is espe- of 750 µW for 8 hours.
Load more

Recommended publications
  • Genetic Testing for Non-Cancerous Inheritable Diseases
    Genetic Testing for Non-Cancerous Inheritable Diseases Policy Number: Original Effective Date: MM.02.009 03/01/2010 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST Integration 12/30/2016 Section: Medicine Place(s) of Service: Outpatient I. Description A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to an inheritable disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing). Genetic tests are conducted for a number of purposes, including predicting disease risk, newborn screening, determining clinical management, identifying carriers, and establishing prenatal or clinical diagnoses or prognoses in individuals, families, or populations. Expanded Carrier Screening The American College of Medical Genetics (ACMG ) defines expanded panels as those that use next- generation sequencing to screen for mutations in many genes, as opposed to gene-by-gene screening (e.g., ethnic-specific screening or panethnic testing for cystic fibrosis). An ACMG position statement states that although commercial laboratories offer expanded carrier screening panels, there has been no professional guidance as to which disease genes and mutations to include. This policy does not address oncology-related genetic testing or pre-implantation genetic diagnosis (PGD). II. Criteria/Guidelines Note: For familial assessments, unless otherwise specified, family will be considered: first-, second- and third- degree relatives on the same side of the family. The maternal and paternal sides should be considered independently.
    [Show full text]
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • Preconception Carrier Screening
    Focusing on Personalised Medicine PRECONCEPTION CARRIER SCREENING Preconception carrier screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases, parents aren’t aware they are carriers and have no family history due to the rarity of some diseases in the general population. What is covered by the screening? Our Inherited Disease Panel tests over 300 genes associated with more than 700 unique commonly inherited diseases, including common forms of inherited deafness, blindness, heart disease, Parkinson’s disease, immunodeficiency, and various ataxias, anaemias, and treatable metabolic syndromes. The assay has been developed in conjunction with clinical molecular geneticists, and includeds genes listed in the NIH Genetic Test Registry. For a full list of genes and disorders covered, please see the reverse of this brochure. Why have Preconception Carrier Screening? Carrier screening prior to pregnancy enables couples to learn about their reproductive risk and consider a complete range of reproductive options, including whether or not to become pregnant, whether to use advanced reproductive technologies, such as preimplantation genetic diagnosis, or use donor gametes. Screening also allows couples to consider prenatal diagnosis and pregnancy management options in the event of an affected fetus. Whilst individually each disease tested is rare, around 25% of people will carry at least one abnormal mutation. These disorders are usually autosomal recessive, which means that a child must inherit a defective gene from each parent to have the disease. For autosomal recessive conditions, if a person is a carrier of the disease, they have one defective copy of the gene and one normal copy and typically don’t have any symptoms of the disease.
    [Show full text]
  • Ophthalmology
    Ophthalmology Information for health professionals MEDICAL GENETIC TESTING FOR OPHTHALMOLOGY Recent technologies, in particularly Next Generation Sequencing (NGS), allows fast, accurate and valuable diagnostic tests. For Ophthalmology, CGC Genetics has an extensive list of medical genetic tests with clinical integration of results by our Medical Geneticists. 1. EXOME SEQUENCING: Exome Sequencing is a very efficient strategy to study most exons of a patient’s genome, unraveling mutations associated with specific disorders or phenotypes. With this diagnostic strategy, patients can be studied with a significantly reduced turnaround time and cost. CGC Genetics has available 2 options for Exome Sequencing: • Whole Exome Sequencing (WES), which analyzes the entire exome (about 20 000 genes); • Disease Exome by CGC Genetics, which analyzes about 6 000 clinically-relevant genes. Any of these can be performed in the index case or in a Trio. 2. NGS PANELS For NGS panels, several genes associated with the same phenotype are simultaneously sequenced. These panels provide increased diagnostic capability with a significantly reduced turnaround time and cost. CGC Genetics has several NGS panels for Ophthalmology that are constantly updated (www.cgcgenetics.com). Any gene studied in exome or NGS panel can also be individually sequenced and analyzed for deletion/duplication events. 3. EXPERTISE IN MEDICAL GENETICS CGC Genetics has Medical Geneticists specialized in genetic counseling for ophthalmological diseases who may advice in choosing the most appropriate
    [Show full text]
  • Diseases of the Digestive System (KOO-K93)
    CHAPTER XI Diseases of the digestive system (KOO-K93) Diseases of oral cavity, salivary glands and jaws (KOO-K14) lijell Diseases of pulp and periapical tissues 1m Dentofacial anomalies [including malocclusion] Excludes: hemifacial atrophy or hypertrophy (Q67.4) K07 .0 Major anomalies of jaw size Hyperplasia, hypoplasia: • mandibular • maxillary Macrognathism (mandibular)(maxillary) Micrognathism (mandibular)( maxillary) Excludes: acromegaly (E22.0) Robin's syndrome (087.07) K07 .1 Anomalies of jaw-cranial base relationship Asymmetry of jaw Prognathism (mandibular)( maxillary) Retrognathism (mandibular)(maxillary) K07.2 Anomalies of dental arch relationship Cross bite (anterior)(posterior) Dis to-occlusion Mesio-occlusion Midline deviation of dental arch Openbite (anterior )(posterior) Overbite (excessive): • deep • horizontal • vertical Overjet Posterior lingual occlusion of mandibular teeth 289 ICO-N A K07.3 Anomalies of tooth position Crowding Diastema Displacement of tooth or teeth Rotation Spacing, abnormal Transposition Impacted or embedded teeth with abnormal position of such teeth or adjacent teeth K07.4 Malocclusion, unspecified K07.5 Dentofacial functional abnormalities Abnormal jaw closure Malocclusion due to: • abnormal swallowing • mouth breathing • tongue, lip or finger habits K07.6 Temporomandibular joint disorders Costen's complex or syndrome Derangement of temporomandibular joint Snapping jaw Temporomandibular joint-pain-dysfunction syndrome Excludes: current temporomandibular joint: • dislocation (S03.0) • strain (S03.4) K07.8 Other dentofacial anomalies K07.9 Dentofacial anomaly, unspecified 1m Stomatitis and related lesions K12.0 Recurrent oral aphthae Aphthous stomatitis (major)(minor) Bednar's aphthae Periadenitis mucosa necrotica recurrens Recurrent aphthous ulcer Stomatitis herpetiformis 290 DISEASES OF THE DIGESTIVE SYSTEM Diseases of oesophagus, stomach and duodenum (K20-K31) Ill Oesophagitis Abscess of oesophagus Oesophagitis: • NOS • chemical • peptic Use additional external cause code (Chapter XX), if desired, to identify cause.
    [Show full text]
  • Orphanet Report Series Rare Diseases Collection
    Marche des Maladies Rares – Alliance Maladies Rares Orphanet Report Series Rare Diseases collection DecemberOctober 2013 2009 List of rare diseases and synonyms Listed in alphabetical order www.orpha.net 20102206 Rare diseases listed in alphabetical order ORPHA ORPHA ORPHA Disease name Disease name Disease name Number Number Number 289157 1-alpha-hydroxylase deficiency 309127 3-hydroxyacyl-CoA dehydrogenase 228384 5q14.3 microdeletion syndrome deficiency 293948 1p21.3 microdeletion syndrome 314655 5q31.3 microdeletion syndrome 939 3-hydroxyisobutyric aciduria 1606 1p36 deletion syndrome 228415 5q35 microduplication syndrome 2616 3M syndrome 250989 1q21.1 microdeletion syndrome 96125 6p subtelomeric deletion syndrome 2616 3-M syndrome 250994 1q21.1 microduplication syndrome 251046 6p22 microdeletion syndrome 293843 3MC syndrome 250999 1q41q42 microdeletion syndrome 96125 6p25 microdeletion syndrome 6 3-methylcrotonylglycinuria 250999 1q41-q42 microdeletion syndrome 99135 6-phosphogluconate dehydrogenase 67046 3-methylglutaconic aciduria type 1 deficiency 238769 1q44 microdeletion syndrome 111 3-methylglutaconic aciduria type 2 13 6-pyruvoyl-tetrahydropterin synthase 976 2,8 dihydroxyadenine urolithiasis deficiency 67047 3-methylglutaconic aciduria type 3 869 2A syndrome 75857 6q terminal deletion 67048 3-methylglutaconic aciduria type 4 79154 2-aminoadipic 2-oxoadipic aciduria 171829 6q16 deletion syndrome 66634 3-methylglutaconic aciduria type 5 19 2-hydroxyglutaric acidemia 251056 6q25 microdeletion syndrome 352328 3-methylglutaconic
    [Show full text]
  • Oculocutaneous Albinism, a Family Matter Summer Moon, DO,* Katherine Braunlich, DO,** Howard Lipkin, DO,*** Annette Lacasse, DO***
    Oculocutaneous Albinism, A Family Matter Summer Moon, DO,* Katherine Braunlich, DO,** Howard Lipkin, DO,*** Annette LaCasse, DO*** *Dermatology Resident, 3rd year, Botsford Hospital Dermatology Residency Program, Farmington Hills, MI **Traditional Rotating Intern, Largo Medical Center, Largo, FL ***Program Director, Botsford Hospital Dermatology Residency Program, Farmington Hills, MI Disclosures: None Correspondence: Katherine Braunlich, DO; [email protected] Abstract Oculocutaneous albinism (OCA) is a group of autosomal-recessive conditions characterized by mutations in melanin biosynthesis with resultant absence or reduction of melanin in the melanocytes. Herein, we present a rare case of two Caucasian sisters diagnosed with oculocutaneous albinism type 1 (OCA1). On physical exam, the sisters had nominal cutaneous evidence of OCA. This case highlights the difficulty of diagnosing oculocutaneous albinism in Caucasians. Additionally, we emphasize the uncommon underlying genetic mutations observed in individuals with oculocutaneous albinism. 2,5 Introduction people has one of the four types of albinism. of exon 4. Additionally, patient A was found to Oculocutaneous albinism (OCA) is a group of We present a rare case of sisters diagnosed with possess the c.21delC frameshift mutation in the autosomal-recessive conditions characterized by oculocutaneous albinism type 1, emphasizing the C10orf11 gene. Patient B was found to possess the mutations in melanin biosynthesis with resultant uncommon genetic mutations we observed in these same heterozygous mutation and deletion in the two individuals. absence or reduction of melanin in the melanocytes. Figure 1 Melanin-poor, pigment-poor melanocytes phenotypically present as hypopigmentation of the Case Report 1,2 Two Caucasian sisters were referred to our hair, skin, and eyes. dermatology clinic after receiving a diagnosis of There are four genes responsible for the four principal oculocutaneous albinism type 1.
    [Show full text]
  • Albinism: Modern Molecular Diagnosis
    British Journal of Ophthalmology 1998;82:189–195 189 Br J Ophthalmol: first published as 10.1136/bjo.82.2.189 on 1 February 1998. Downloaded from PERSPECTIVE Albinism: modern molecular diagnosis Susan M Carden, Raymond E Boissy, Pamela J Schoettker, William V Good Albinism is no longer a clinical diagnosis. The past cytes and into which melanin is confined. In the skin, the classification of albinism was predicated on phenotypic melanosome is later transferred from the melanocyte to the expression, but now molecular biology has defined the surrounding keratinocytes. The melanosome precursor condition more accurately. With recent advances in arises from the smooth endoplasmic reticulum. Tyrosinase molecular research, it is possible to diagnose many of the and other enzymes regulating melanin synthesis are various albinism conditions on the basis of genetic produced in the rough endoplasmic reticulum, matured in causation. This article seeks to review the current state of the Golgi apparatus, and translocated to the melanosome knowledge of albinism and associated disorders of hypo- where melanin biosynthesis occurs. pigmentation. Tyrosinase is a copper containing, monophenol, mono- The term albinism (L albus, white) encompasses geneti- oxygenase enzyme that has long been known to have a cally determined diseases that involve a disorder of the critical role in melanogenesis.5 It catalyses three reactions melanin system. Each condition of albinism is due to a in the melanin pathway. The rate limiting step is the genetic mutation on a diVerent chromosome. The cutane- hydroxylation of tyrosine into dihydroxyphenylalanine ous hypopigmentation in albinism ranges from complete (DOPA) by tyrosinase, but tyrosinase does not act alone.
    [Show full text]
  • Soonerstart Automatic Qualifying Syndromes and Conditions
    SoonerStart Automatic Qualifying Syndromes and Conditions - Appendix O Abetalipoproteinemia Acanthocytosis (see Abetalipoproteinemia) Accutane, Fetal Effects of (see Fetal Retinoid Syndrome) Acidemia, 2-Oxoglutaric Acidemia, Glutaric I Acidemia, Isovaleric Acidemia, Methylmalonic Acidemia, Propionic Aciduria, 3-Methylglutaconic Type II Aciduria, Argininosuccinic Acoustic-Cervico-Oculo Syndrome (see Cervico-Oculo-Acoustic Syndrome) Acrocephalopolysyndactyly Type II Acrocephalosyndactyly Type I Acrodysostosis Acrofacial Dysostosis, Nager Type Adams-Oliver Syndrome (see Limb and Scalp Defects, Adams-Oliver Type) Adrenoleukodystrophy, Neonatal (see Cerebro-Hepato-Renal Syndrome) Aglossia Congenita (see Hypoglossia-Hypodactylia) Aicardi Syndrome AIDS Infection (see Fetal Acquired Immune Deficiency Syndrome) Alaninuria (see Pyruvate Dehydrogenase Deficiency) Albers-Schonberg Disease (see Osteopetrosis, Malignant Recessive) Albinism, Ocular (includes Autosomal Recessive Type) Albinism, Oculocutaneous, Brown Type (Type IV) Albinism, Oculocutaneous, Tyrosinase Negative (Type IA) Albinism, Oculocutaneous, Tyrosinase Positive (Type II) Albinism, Oculocutaneous, Yellow Mutant (Type IB) Albinism-Black Locks-Deafness Albright Hereditary Osteodystrophy (see Parathyroid Hormone Resistance) Alexander Disease Alopecia - Mental Retardation Alpers Disease Alpha 1,4 - Glucosidase Deficiency (see Glycogenosis, Type IIA) Alpha-L-Fucosidase Deficiency (see Fucosidosis) Alport Syndrome (see Nephritis-Deafness, Hereditary Type) Amaurosis (see Blindness) Amaurosis
    [Show full text]
  • Hereditary Hearing Impairment with Cutaneous Abnormalities
    G C A T T A C G G C A T genes Review Hereditary Hearing Impairment with Cutaneous Abnormalities Tung-Lin Lee 1 , Pei-Hsuan Lin 2,3, Pei-Lung Chen 3,4,5,6 , Jin-Bon Hong 4,7,* and Chen-Chi Wu 2,3,5,8,* 1 Department of Medical Education, National Taiwan University Hospital, Taipei City 100, Taiwan; [email protected] 2 Department of Otolaryngology, National Taiwan University Hospital, Taipei 11556, Taiwan; [email protected] 3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City 100, Taiwan; [email protected] 4 Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei City 100, Taiwan 5 Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan 6 Department of Internal Medicine, National Taiwan University Hospital, Taipei 10041, Taiwan 7 Department of Dermatology, National Taiwan University Hospital, Taipei City 100, Taiwan 8 Department of Medical Research, National Taiwan University Biomedical Park Hospital, Hsinchu City 300, Taiwan * Correspondence: [email protected] (J.-B.H.); [email protected] (C.-C.W.) Abstract: Syndromic hereditary hearing impairment (HHI) is a clinically and etiologically diverse condition that has a profound influence on affected individuals and their families. As cutaneous findings are more apparent than hearing-related symptoms to clinicians and, more importantly, to caregivers of affected infants and young individuals, establishing a correlation map of skin manifestations and their underlying genetic causes is key to early identification and diagnosis of syndromic HHI. In this article, we performed a comprehensive PubMed database search on syndromic HHI with cutaneous abnormalities, and reviewed a total of 260 relevant publications.
    [Show full text]
  • Analysis of Ocular Hypopigmentation in Rab38cht/Cht Mice
    ARTICLES Analysis of Ocular Hypopigmentation in Rab38cht/cht Mice Brian P. Brooks,1,2,3 Denise M. Larson,2,3 Chi-Chao Chan,1 Sten Kjellstrom,4 Richard S. Smith,5,6 Mary A. Crawford,1 Lynn Lamoreux,7 Marjan Huizing,3 Richard Hess,3 Xiaodong Jiao,1 J. Fielding Hejtmancik,1 Arvydas Maminishkis,1 Simon W. M. John,5,6 Ronald Bush,4 and William J. Pavan3 cht PURPOSE. To characterize the ocular phenotype resulting from and RPE thinning. The synergistic effects of the Rab38 and mutation of Rab38, a candidate gene for Hermansky-Pudlak Tyrp1b alleles suggest that TYRP1 is not the only target of syndrome. RAB38 trafficking. This mouse line provides a useful model for cht/cht METHODS. Chocolate mice (cht, Rab38 ) and control het- studying melanosome biology and its role in human ocular erozygous (Rab38cht/ϩ) and wild-type mice were examined diseases. (Invest Ophthalmol Vis Sci. 2007;48:3905–3913) clinically, histologically, ultrastructurally, and electrophysi- DOI:10.1167/iovs.06-1464 ologically. Mice homozygous for both the Rab38cht and the Tyrp1b alleles were similarly examined. he analysis of mice that exhibit defects in coat coloration cht/cht RESULTS. Rab38 mice showed variable peripheral iris trans- T(coat color mutants) has aided in the identification of 1 illumination defects at 2 months of age. Patches of RPE hypo- genes important in eye, skin, and hair pigmentation. Many of pigmentation were noted clinically in 57% of Rab38cht/cht eyes these genes are mutated in patients with pigmentary anoma- and 6% of Rab38cht/ϩ eyes. Rab38cht/cht mice exhibited thin- lies.
    [Show full text]
  • Visual Impairment Age-Related Macular
    VISUAL IMPAIRMENT AGE-RELATED MACULAR DEGENERATION Macular degeneration is a medical condition predominantly found in young children in which the center of the inner lining of the eye, known as the macula area of the retina, suffers thickening, atrophy, and in some cases, watering. This can result in loss of side vision, which entails inability to see coarse details, to read, or to recognize faces. According to the American Academy of Ophthalmology, it is the leading cause of central vision loss (blindness) in the United States today for those under the age of twenty years. Although some macular dystrophies that affect younger individuals are sometimes referred to as macular degeneration, the term generally refers to age-related macular degeneration (AMD or ARMD). Age-related macular degeneration begins with characteristic yellow deposits in the macula (central area of the retina which provides detailed central vision, called fovea) called drusen between the retinal pigment epithelium and the underlying choroid. Most people with these early changes (referred to as age-related maculopathy) have good vision. People with drusen can go on to develop advanced AMD. The risk is considerably higher when the drusen are large and numerous and associated with disturbance in the pigmented cell layer under the macula. Recent research suggests that large and soft drusen are related to elevated cholesterol deposits and may respond to cholesterol lowering agents or the Rheo Procedure. Advanced AMD, which is responsible for profound vision loss, has two forms: dry and wet. Central geographic atrophy, the dry form of advanced AMD, results from atrophy to the retinal pigment epithelial layer below the retina, which causes vision loss through loss of photoreceptors (rods and cones) in the central part of the eye.
    [Show full text]