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Original Investigation | Clinical Sciences

Waardenburg Syndrome: Iris and Choroidal Hypopigmentation Findings on Anterior and Posterior Segment Imaging FREE

Carol L. Shields, MD1; Stephanie J. Nickerson, BA1; Saad Al-Dahmash, MD1,2; Jerry A. Shields, MD1
[+] Author Affiliations
1Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania
2Department of Ophthalmology, College of Medicine, King Saud University, Saudi Arabia
JAMA Ophthalmol. 2013;131(9):1167-1173. doi:10.1001/jamaophthalmol.2013.4190.
Text Size: A A A
Published online

Importance  Waardenburg syndrome typically manifests with congenital iris pigmentary abnormalities, but careful inspection can reveal additional posterior uveal pigmentary abnormalities.

Objective  To demonstrate iris and choroidal hypopigmentation in patients with Waardenburg syndrome.

Design, Setting, and Participants  Retrospective review of 7 patients referred for evaluation of presumed ocular melanocytosis.

Main Outcomes and Measures  To describe the clinical and imaging features of the anterior and posterior uvea.

Results  In all patients, the diagnosis of Waardenburg syndrome was established. The nonocular features included white forelock in 4 of 7 (57%), tubular nose in 5 of 6 (83%), and small nasal alae in 5 of 6 (83%) patients. In 2 patients, a hearing deficit was documented on audiology testing. Family history of Waardenburg syndrome was elicited in 5 of 7 (71%) patients. Ocular features (7 patients) included telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%), and choroidal hypopigmentation in 5 (71%) patients. No patient had muscle contractures or Hirschsprung disease. Visual acuity was 20/20 to 20/50 in all patients. Iris hypopigmentation in 8 eyes was sector in 6 (75%) and diffuse (complete) in 2 (25%). Choroidal hypopigmentation in 9 eyes (100%) showed a sector pattern in 6 (67%) and a diffuse pattern in 3 (33%). Anterior segment optical coherence tomography revealed the hypopigmented iris to be thinner and with shallower crypts than the normal iris. Posterior segment optical coherence tomography showed a normal retina in all patients, but the subfoveal choroid in the hypopigmented region was slightly thinner (mean, 197 μm) compared with the opposite normal choroid (243 μm). Fundus autofluorescence demonstrated mild hyperautofluorescence (scleral unmasking) in hypopigmented choroid and no lipofuscin abnormality.

Conclusions and Relevance  Waardenburg syndrome manifests hypopigmentation of the iris and choroid with imaging features showing a slight reduction in the thickness of the affected tissue.

Figures in this Article

In 1951, Waardenburg published a description of a new syndrome of developmental anomalies of the eyelids, eyebrows, nasal root, iris, and scalp hair associated with congenital deafness, now called Waardenburg syndrome (WS).1 In a 59-page document published in the American Journal of Human Genetics, Waardenburg delineated important distinguishing ocular findings. He opened his report with a description of a 72-year-old deaf-mute proband patient with epiphora from telecanthus. Waardenburg recognized the striking midline white hair of his patient and the family members. His second patient, found 1 year later from the clinic of Professor Franceschetti in Geneva, Switzerland, was a 10-year-old deaf-mute girl with telecanthus, a white forelock, and cutaneous “partial albinism.”

Waardenburg1 further delineated the 6 chief characteristics of WS, including (1) telecanthus (lateral displacement of the medial canthus), (2) a broad nasal root, (3) synophrys of the eyebrows, (4) a white forelock (termed piebaldism), (5) heterochromia irides, and (6) deaf-mutism. In the initial description, Waardenburg described the eye findings as “heterochromia iridum totalis sive partialis,” with total or partial pigmentary disturbance. There was minimal comment on choroidal findings, with a minor remark that the choroid “seemed to take part in the pigment defect in a minor degree.”1(p240) Subsequent studies have documented variable expressivity of the clinical findings in WS.2,3

Not many publications have addressed the ocular features of WS, mostly focusing on the abnormalities of the iris. Few reports have presented details of the fundus findings, often with small-angle photographic documentation showing the macular region and without representation of the entire fundus.47 We have observed broad areas of choroidal hypopigmentation with WS. Herein, we document the striking iris and choroidal findings in patients with WS using wide-angle montage fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). These ocular pigmentary features should be recognizable to the ophthalmologist, providing a clue to the underlying diagnosis.6

We reviewed the medical records of patients with a clinical diagnosis of WS, examined at the Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, Philadelphia, Pennsylvania. Criteria for diagnosis of WS were based on the Waardenburg Consortium,8 indicating that affected individuals demonstrate at least 2 major criteria or 1 major criterion plus 2 minor criteria (Table 1).

Table Graphic Jump LocationTable 1.  Diagnostic Criteria for Waardenburg Syndrome Type 1a

The demographic information included patient age, race, sex, and family history of WS. Each patient was specifically examined for simulating conditions of ocular melanocytosis, albinism, vitiligo, autoimmune disease, previous inflammation, uveal or cutaneous melanoma, or other pigmentary conditions. The nonocular data included the presence of cutaneous pigmentary defects, deafness (confirmed by audiology testing), a tubular nasal bridge, and small nasal alae. The ocular data included visual acuity; the presence of telecanthus, synophrys, iris hypopigmentation, and choroidal hypopigmentation; and retinal and retinal pigment epithelial findings. The iris was specifically assessed for intrinsic color and hypopigmentation features, including pattern (diffuse or sector), number of clock-hours, quadrant, and symmetry with the opposite eye. The choroid was specifically assessed for hypopigmentation features, including pattern (diffuse or sector), percentage of the affected fundus, largest basal diameter (in millimeters), quadrant, and symmetry with the opposite eye.

Imaging was performed (when necessary and available) using anterior segment OCT (AS-OCT) (Visante OCT 3.0; Carl Zeiss Meditec), with an illumination laser source of 1310 nm; posterior segment OCT (Heidelberg Spectralis HRA+OCT; Heidelberg Engineering); and fundus autofluorescence (Topcon TRC-50DX Retinal Camera; Topcon America), with an excitation light bandwidth of 535 to 585 nm and a barrier filter bandwidth of 605 to 715 nm. Wide-angle montage fundus photography was carried out when available. We compared the appearance and thickness of the iris tissue in the hypopigmented vs normal iris, OCT of the retina and choroidal features and thickness in the hypopigmented vs normal foveal choroid, and autofluorescence features in the hypopigmented vs normal choroid. Institutional review board permission from Wills Eye Institute was obtained.

All 7 patients had bilateral findings. Patients included 5 (71%) whites, 1 (15%) Hispanic, and 1 (15%) African American, with 3 (43%) males and 4 (57%) females. The mean age at presentation was 32 years (median, 43 years; range, 1-66 years) (Table 2). Visual acuity was 20/20 in 10 (71%) eyes and 20/25 to 20/50 in 4 (29%) eyes. All 7 patients were referred with the presumed diagnosis of ocular melanocytosis.

Table Graphic Jump LocationTable 2.  General Manifestations of Waardenburg Syndrome in 7 Patients From 6 Families

All patients met diagnostic criteria for WS (Table 1). No patient had muscle contractures (type 3 WS) or Hirschsprung disease (type 4 WS). The general manifestations of nonocular and ocular tissues are listed in Table 2. The ocular features include telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%), choroid hypopigmentation in 5 (71%), and focal retinal pigment epithelial loss in 4 (57%) patients (Figures 1, 2, and 3). The specific iris and choroidal features are presented in Table 3. Of the 8 eyes with iris hypopigmentation, the pattern was sector in 6 (75%) and diffuse (complete) in 2 (25%) (Figure 1). The sector iris hypopigmentation involved 3 to 11 clock-hours (mean, 6.2 clock-hours), with minimal symmetry of the pigmentary abnormality between the 2 irides.

Place holder to copy figure label and caption
Figure 1.
Spectrum of Iris and Choroidal Hypopigmentation in a Lightly Pigmented African American Boy With Waardenburg Syndrome

At age 1 year, blue irides, synophrys, and telecanthus (A) were noted and unchanged at 7 years (B). At age 1 year, a hypopigmented scalp forelock (C) evolved to scattered subtle white scalp hairs (D) at 7 years. At ages 1 and 7 years, the iris features were stable, with sector depigmentation involving nearly 11 clock-hours and with minimal residual brown superotemporally in the right eye (E) and inferonasally in the left eye (F), leaving brilliant blue irides of Waardenburg syndrome. Family members showed the same.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Choroidal Hypopigmentation in a Father and Daughter With Waardenburg Syndrome

A dark-haired 66-year-old Hispanic man with no iris defect, unrelated bilateral pterygium (A), telecanthus, mild synophrys, and congenital white forelock (B) treated with black hair dye. His daughter had the same white forelock but no eye examination. Wide-angle montage fundus photography documented a postequatorial hypopigmented choroid in the right (C) and left (D) eyes, with scattered focal retinal pigment epithelial atrophic spots. Fundus autofluorescence revealed slight hyperautofluorescence through the hypopigmented choroidal region in the right (E) and left (F) eyes, indicating unmasking of scleral autofluorescence. Enhanced depth imaging optical coherence tomography of the right (G) and left (H) eyes demonstrated normal retina in both eyes and slight thinning of choroidal tissue to approximately 175 to 180 μm in each eye.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Features of Waardenburg Syndrome in a Mother and Daughter

A 43-year-old woman with no iris heterochromia (A) and sector choroidal hypopigmentation superiorly in the right (B) and left (C) eyes. The 13-year-old daughter had sector heterochromia (D) with anterior segment optical coherence tomography (horizontal orientation) documenting normal thickness of the normal brown iris (E) and a thin, flatter appearance of the affected, hypopigmented right (E) and left (F) irides. Funduscopically, there was symmetric choroidal hypopigmentation in the right (G) and left (H) eyes.

Graphic Jump Location
Table Graphic Jump LocationTable 3.  Specific Iris and Choroidal Findings of Waardenburg Syndrome in 7 Patients From 6 Families

Choroidal hypopigmentation, detected in 9 eyes, showed a sector pattern in 6 (67%) and a diffuse pattern in 3 (33%) (Figure 2 and Figure 3). The sector choroidal hypopigmentation was estimated using ophthalmoscopy at 20% to 80% (mean, 73%) of the fundus with a basal dimension of 10 to 22 mm (mean, 19 mm). The quadrants of choroidal hypopigmentation were postequatorial (n = 2), superotemporal (n = 2), nasal (n = 2), and the entire fundus (n = 3). All bilateral cases of choroidal hypopigmentation (8 eyes) had symmetry of the pigmentary abnormality. The iris hypopigmentation showed little correlation with choroidal hypopigmentation.

Using AS-OCT in 4 eyes, the hypopigmented iris was slightly thinner and with more shallow crypts than the normal iris (Table 4). Using posterior segment OCT, the subfoveal choroid was slightly (19%) thinner (mean, 197 μm) in the affected eye compared with the normal subfoveal choroid (243 μm) in the opposite eye. The retina was intact in all patients. Fundus autofluorescence demonstrated mild homogeneous hyperautofluorescence (scleral unmasking) in the hypopigmented choroid and no lipofuscin abnormality.

Table Graphic Jump LocationTable 4.  Ocular Imaging of the Iris and Choroid in Waardenburg Syndrome in 7 Patients From 6 Families

No patient showed features of albinism, vitiligo, autoimmune disease, previous inflammation, other pigmentary conditions, or ocular melanocytosis, including scleral, dermal, or palatal pigmentation. None of the patients had iris mammillations or equatorial drusen.

Waardenburg syndrome type 1 (WS1; OMIM 193500) is a highly penetrant autosomal dominant condition with major and minor features (Table 1). The phenotype of WS is variable, with 4 specific types, labeled WS1, WS2, WS3, and WS4.9 The features of WS1 include telecanthus; pigmentary abnormalities of the hair, skin, and eyes; and congenital deafness, as listed in Table 1. Those with WS2 are similar to patients with WS1 but lack telecanthus. Two much less common types include WS3 (Klein-Waardenburg syndrome), which also shows features of severe limb abnormalities and contractures, and WS4 (Waardenburg-Shah syndrome), with additional Hirschsprung disease. Identified genetic mutations in the PAX3 gene can lead to WS1 and WS3.1012 Mutations in MITF and SNAI2 lead to WS2. Type 4 WS is related to multiple mutations in SOX10, EDN3, or EDNRB.1012

Clinical variability is common with WS, even within affected members of a single family.3 In an analysis of 26 patients diagnosed with WS1, features included telecanthus (82%), white forelock (24%), skin hypopigmentation (30%), iris heterochromia (32%), synophrys (78%), and hypoplastic nasal alae (92%).3 More severe deafness correlated with more extensive iris heterochromia.3

The ophthalmic pigmentary abnormalities in WS initially were described as iris heterochromia (complete or sector) and “minor choroidal findings.”1 In 1966, Goldberg5 reviewed the ophthalmic findings in 14 patients from 7 families with WS and discovered a variety of sector and complete hypopigmentary features of the iris and the “fundus,” often parallel in the degree of pigmentation. For example, a blue iris was generally associated with a blond or “albinoid” fundus. Goldberg stated that the fundus pigmentary abnormalities constituted an integral part of WS. In 1978, Delleman and Hageman6 reviewed the ophthalmic findings in WS in 34 patients from 5 families and found 59% (20 of 34) with pigmentary disorders, including 15 with pigmentary iris abnormalities and 3 with hypoplastic blue irides bilaterally. Fundus examination revealed hypopigmentation in 67% (10 of 15).6 There was no further description of the extent, location, or pattern of alterations. Delleman and Hageman summarized their findings by stating that “10 of the 15 patients with pigmentary disorders of the iris also showed a shortage of pigment in the retina,”6(p345) but we presume that it was actually the choroid.

There is some confusion in the literature about the terminology regarding the fundus and the external features. The term piebaldism has been used to denote the white forelock and loosely describes the pigmentary abnormalities of the iris. The word piebaldism, which implies multicolored, refers to the black and white feathers of a magpie (pie), and the term bald indicates a white spot or patch.13,14 This term aptly describes the white forelock on a black-haired scalp. Furthermore, piebaldism is not descriptive of the iris or choroidal findings because these features do not involve black or white. A more appropriate term would simply be hypopigmentation since the normal brown or green iris is congenitally hypopigmented as blue.

The abnormalities of the iris in WS have been documented on electron microscopy to represent fewer melanocytes in the hypopigmented blue region compared with the normal brown region, and a substantial reduction in the melanosome size in the blue region is believed to be related to a defect in neural crest cell migration and melanin production.15 In our case series, 1 patient showed a bilateral “brilliant blue” iris, and 1 showed unilateral “blue” features. The remainder showed sectoral or no clinical defect in the iris. Imaging of the iris with AS-OCT confirmed a slightly thinner iris with less obvious crypt formation in the depigmented “blue” region.

The choroidal pigmentary features were striking in this case series. Of the 7 patients with WS, 5 had choroidal hypopigmentation, which was often sectoral, involving large portions of the choroid with a symmetric distribution. Foveal OCT disclosed that the hypopigmented choroid was slightly (19%) thinner compared with the normal opposite subfoveal counterpart. Fundus autofluorescence displayed mild hyperautofluorescence from slight unmasking of scleral autofluorescence, as seen with an amelanotic nevus.16 There was no visible lipofuscin abnormality on autofluorescence.

In addition to WS, several other conditions related to iris and choroidal pigmentary abnormalities can be included in the differential diagnosis. Some iris pigmentary abnormalities that could simulate the iris features of WS include iris freckles, nevus (circumscribed, sector, and diffuse), melanoma (circumscribed and diffuse), melanocytosis (sector and diffuse), Fuch heterochromic iridocyclitis, Horner syndrome, and topical medication (latanoprost). Some choroidal pigmentary abnormalities that could simulate the choroidal features in WS include choroid nevus, melanoma, melanocytosis (complete and sector), vitiligo, and Vogt-Koyanagi-Harada syndrome.1721 Ocular melanocytosis most closely simulates the eye features of WS since both are congenital and can be unilateral or bilateral and diffuse, sectoral, or patchy. However, melanocytosis involves hyperpigmentation of uveal tissue, whereas WS involves hypopigmentation. In addition, hyperpigmentation of scleral, dermal, or palatal tissue often occurs in melanocytosis but is not found with WS. In melanocytosis, the darker portion of the iris can show dense mammillations with loss of crypts, the darker portion of the choroid eventually demonstrates drusen, and there is a small risk for melanoma. With WS, there is the addition of family history, canthal location, and nonocular findings in the scalp, nasal bridge, and eyebrow. Furthermore, in WS, there is relative preservation of iris crypts, a lack of equatorial drusen, and no increased risk for melanoma. All 7 patients in this series were referred for evaluation of presumed ocular melanocytosis, and following our history and examination, the diagnosis of WS was established. All patients were recommended to have genetic evaluation, but each declined.

Limitations in our observations should be identified. We describe our findings in a small cohort of patients, but a larger cohort could provide more reliable results. In addition, our findings could be biased by referral due to our interest in pigmented lesions of the eye. The relative frequency of each finding would be better studied by examining a large cohort of patients with known WS. Furthermore, genetic testing was not obtained due to patient preference.

In conclusion, we have described and illustrated the broad spectrum of iris and choroidal hypopigmentation as part of WS. We have documented the features with wide-angle montage fundus photography, AS-OCT, posterior segment OCT, and autofluorescence. Despite the broad range of abnormalities in this condition, visual acuity generally remains intact.

Submitted for Publication: November 16, 2012; final revision received February 17, 2013; accepted February 20, 2013.

Corresponding Author: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, 840 Walnut St, Ste 1440, Philadelphia, PA 19107 (carol.shields@shieldsoncology.com)

Published Online: July 18, 2013. doi:10.1001/jamaophthalmol.2013.4190.

Author Contributions: Drs C. L. Shields and Al-Dahmash had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: C. L. Shields, Al-Dahmash.

Acquisition of data: C. L. Shields, Al-Dahmash.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: C. L. Shields, Nickerson, Al-Dahmash.

Critical revision of the manuscript for important intellectual content: C. L. Shields, J. A. Shields.

Statistical analysis: C. L. Shields, Nickerson, Al-Dahmash.

Obtained funding: C. L. Shields.

Administrative, technical, and material support: C. L. Shields, J. A. Shields.

Study supervision: C. L. Shields, J. A. Shields.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by the Eye Tumor Research Foundation (Drs C. L. Shields and J. A. Shields); the Lucille Wiedman Fund for Pediatric Cancer (Drs C. L. Shields and J. A. Shields); and the Ocular Oncology Fund, Wills Eye Institute.

Role of the Sponsor: The funders had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; and in the preparation, review, or approval of the manuscript.

Waardenburg  PJ.  A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet. 1951;3(3):195-253.
PubMed
Hageman  MJ, Delleman  JW.  Heterogeneity in Waardenburg syndrome. Am J Hum Genet. 1977;29(5):468-485.
PubMed
Reynolds  JE, Marazita  ML, Meyer  JM,  et al.  Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome. Am J Hum Genet. 1996;58(2):384-392.
PubMed
Digeorge  AM, Olmsted  RW, Harley  RD.  Waardenburg’s syndrome: a syndrome of heterochromia of the iridies, lateral displacement of the medial canthi and lacrimal puncta, congenital deafness, and other characteristic associated defects. Trans Am Acad Ophthalmol Otolaryngol. 1960;64:816-839.
PubMed
Goldberg  MF.  Waardenburg’s syndrome with fundus and other anomalies. Arch Ophthalmol. 1966;76(6):797-810.
PubMed   |  Link to Article
Delleman  JW, Hageman  MJ.  Ophthalmological findings in 34 patients with Waardenburg syndrome. J Pediatr Ophthalmol Strabismus. 1978;15(6):341-345.
PubMed
Müllner-Eidenböck  A, Moser  E, Frisch  H, Read  AP.  Waardenburg syndrome type 2 in a Turkish family: implications for the importance of the pattern of fundus pigmentation. Br J Ophthalmol. 2001;85(11):1384-1386.
PubMed   |  Link to Article
Farrer  LA, Grundfast  KM, Amos  J,  et al.  Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet. 1992;50(5):902-913.
PubMed
Arias  S.  Genetic heterogeneity in the Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971;7(4):87-101.
Farrer  LA, Arnos  KS, Asher  JH  Jr,  et al.  Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes. Am J Hum Genet. 1994;55(4):728-737.
PubMed
Bondurand  N, Pingault  V, Goerich  DE,  et al.  Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. 2000;9(13):1907-1917.
PubMed   |  Link to Article
Pingault  V, Ente  D, Dastot-Le Moal  F, Goossens  M, Marlin  S, Bondurand  N.  Review and update of mutations causing Waardenburg syndrome. Hum Mutat. 2010;31(4):391-406.
PubMed   |  Link to Article
Picket  JP, ed. The American Heritage Dictionary of the English Language.4th ed. New York, NY: Houghton Mifflin; 2000:1329, 1630.
Oxford Dictionary of English, Version 2.2.3 (118.5). Cupertino, CA: Apple; 2011.
Mullaney  PB, Parsons  MA, Weatherhead  RG, Karcioglu  ZA.  Clinical and morphological features of Waardenburg syndrome type II. Eye (Lond). 1998;12(pt 3a):353-357.
PubMed   |  Link to Article
Shields  CL, Pirondini  C, Bianciotto  C, Materin  MA, Harmon  SA, Shields  JA.  Autofluorescence of choroidal nevus in 64 cases. Retina. 2008;28(8):1035-1043.
PubMed   |  Link to Article
Li  HK, Shields  CL, Mashayekhi  A,  et al.  Giant choroidal nevus clinical features and natural course in 322 cases. Ophthalmology. 2010;117(2):324-333.
PubMed   |  Link to Article
Shields  CL, Shields  JA, De Potter  P, Cater  J, Tardio  D, Barrett  J.  Diffuse choroidal melanoma: clinical features predictive of metastasis. Arch Ophthalmol. 1996;114(8):956-963.
PubMed   |  Link to Article
Shields  CL, Kaliki  S, Furuta  M, Shields  JA.  Diffuse versus non-diffuse small (≤3 millimeters thickness) choroidal melanoma: comparative analysis in 1751 cases: the 2012 F. Phinizy Calhoun Lecture [published online April 11, 2013]. Retina.
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Shields  CL, Qureshi  A, Mashayekhi  A,  et al.  Sector (partial) oculo(dermal) melanocytosis in 89 eyes. Ophthalmology. 2011;118(12):2474-2479.
PubMed   |  Link to Article
Shields  CL, Ramasubramanian  A, Kunz  WB, Aggarwal  E, Shields  JA.  Choroidal vitiligo masquerading as large choroidal nevus: a report of four cases. Ophthalmology. 2010;117(1):109-113, e3.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Spectrum of Iris and Choroidal Hypopigmentation in a Lightly Pigmented African American Boy With Waardenburg Syndrome

At age 1 year, blue irides, synophrys, and telecanthus (A) were noted and unchanged at 7 years (B). At age 1 year, a hypopigmented scalp forelock (C) evolved to scattered subtle white scalp hairs (D) at 7 years. At ages 1 and 7 years, the iris features were stable, with sector depigmentation involving nearly 11 clock-hours and with minimal residual brown superotemporally in the right eye (E) and inferonasally in the left eye (F), leaving brilliant blue irides of Waardenburg syndrome. Family members showed the same.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Choroidal Hypopigmentation in a Father and Daughter With Waardenburg Syndrome

A dark-haired 66-year-old Hispanic man with no iris defect, unrelated bilateral pterygium (A), telecanthus, mild synophrys, and congenital white forelock (B) treated with black hair dye. His daughter had the same white forelock but no eye examination. Wide-angle montage fundus photography documented a postequatorial hypopigmented choroid in the right (C) and left (D) eyes, with scattered focal retinal pigment epithelial atrophic spots. Fundus autofluorescence revealed slight hyperautofluorescence through the hypopigmented choroidal region in the right (E) and left (F) eyes, indicating unmasking of scleral autofluorescence. Enhanced depth imaging optical coherence tomography of the right (G) and left (H) eyes demonstrated normal retina in both eyes and slight thinning of choroidal tissue to approximately 175 to 180 μm in each eye.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.
Features of Waardenburg Syndrome in a Mother and Daughter

A 43-year-old woman with no iris heterochromia (A) and sector choroidal hypopigmentation superiorly in the right (B) and left (C) eyes. The 13-year-old daughter had sector heterochromia (D) with anterior segment optical coherence tomography (horizontal orientation) documenting normal thickness of the normal brown iris (E) and a thin, flatter appearance of the affected, hypopigmented right (E) and left (F) irides. Funduscopically, there was symmetric choroidal hypopigmentation in the right (G) and left (H) eyes.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1.  Diagnostic Criteria for Waardenburg Syndrome Type 1a
Table Graphic Jump LocationTable 2.  General Manifestations of Waardenburg Syndrome in 7 Patients From 6 Families
Table Graphic Jump LocationTable 3.  Specific Iris and Choroidal Findings of Waardenburg Syndrome in 7 Patients From 6 Families
Table Graphic Jump LocationTable 4.  Ocular Imaging of the Iris and Choroid in Waardenburg Syndrome in 7 Patients From 6 Families

References

Waardenburg  PJ.  A new syndrome combining developmental anomalies of the eyelids, eyebrows and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet. 1951;3(3):195-253.
PubMed
Hageman  MJ, Delleman  JW.  Heterogeneity in Waardenburg syndrome. Am J Hum Genet. 1977;29(5):468-485.
PubMed
Reynolds  JE, Marazita  ML, Meyer  JM,  et al.  Major-locus contributions to variability of the craniofacial feature dystopia canthorum in Waardenburg syndrome. Am J Hum Genet. 1996;58(2):384-392.
PubMed
Digeorge  AM, Olmsted  RW, Harley  RD.  Waardenburg’s syndrome: a syndrome of heterochromia of the iridies, lateral displacement of the medial canthi and lacrimal puncta, congenital deafness, and other characteristic associated defects. Trans Am Acad Ophthalmol Otolaryngol. 1960;64:816-839.
PubMed
Goldberg  MF.  Waardenburg’s syndrome with fundus and other anomalies. Arch Ophthalmol. 1966;76(6):797-810.
PubMed   |  Link to Article
Delleman  JW, Hageman  MJ.  Ophthalmological findings in 34 patients with Waardenburg syndrome. J Pediatr Ophthalmol Strabismus. 1978;15(6):341-345.
PubMed
Müllner-Eidenböck  A, Moser  E, Frisch  H, Read  AP.  Waardenburg syndrome type 2 in a Turkish family: implications for the importance of the pattern of fundus pigmentation. Br J Ophthalmol. 2001;85(11):1384-1386.
PubMed   |  Link to Article
Farrer  LA, Grundfast  KM, Amos  J,  et al.  Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: first report of the WS consortium. Am J Hum Genet. 1992;50(5):902-913.
PubMed
Arias  S.  Genetic heterogeneity in the Waardenburg syndrome. Birth Defects Orig Artic Ser. 1971;7(4):87-101.
Farrer  LA, Arnos  KS, Asher  JH  Jr,  et al.  Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes. Am J Hum Genet. 1994;55(4):728-737.
PubMed
Bondurand  N, Pingault  V, Goerich  DE,  et al.  Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Mol Genet. 2000;9(13):1907-1917.
PubMed   |  Link to Article
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