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ciliopathy and that a happy demeanor may be a presentingfeature of the phenotype.

References

1. Schmidts M, Frank V, Eisenberger T, et al. Combined NGSapproaches identify mutations in the intraflagellar transport geneIFT140 in skeletal ciliopathies with early progressive kidney. DiseaseHum Mutat 2013;34:714-24.

2. Perrault I, Saunier S, Hanein S, et al. Mainzer-Saldino syndrome is aciliopathy caused by IFT140 mutations. Am J Hum Genet 2012;90:864-70.

3. Mockel A, Perdomo Y, Stutzmann F, Letsch J, Marion V, Dollfus H.Retinal dystrophy in Bardet-Biedl syndrome and related syndromicciliopathies. Prog Retin Eye Res 2011;30:258-74.

4. Dagoneau N, Goulet M, Genevieve D, et al. DYNC2H1 mutationscause asphyxiating thoracic dystrophy and short rib-polydactyly syn-drome, type III. Am J Hum Genet 2009;84:706-11.

5. Merrill AE, Merriman B, Farrington-Rock C, et al. Ciliary abnor-malities due to defects in the retrograde transport proteinDYNC2H1 in short-rib polydactyly syndrome. Am J Hum Genet2009;84:542-9.

6. Beales PL, Bland E, Tobin JL, et al. IFT80, which encodes a conservedintraflagellar transport protein, is mutated in Jeune asphyxiatingthoracic dystrophy. Nat Genet 2007;39:727-9.

7. DavisEE,ZhangQ,LiuQ,etal.TTC21Bcontributesbothcausal andmodi-fying alleles across the ciliopathy spectrum. Nat Genet 2011;43:189-96.

8. Bredrup C, Saunier S, OudMM, et al. Ciliopathies with skeletal anom-alies and renal insufficiency due to mutations in the IFT-A geneWDR19. Am J Hum Genet 2011;89:634-43.

9. Khan AO, Oystreck DT, SeidahmedMZ, et al. Ophthalmic features ofJoubert syndrome. Ophthalmology 2008;115:2286-9.

Ophthalmologic findings in an18-month-old boy with focaldermal hypoplasiaMarielle P. Young, MD, Briana L. Sawyer, MS,and M. Elizabeth Hartnett, MD

Focal dermal hypoplasia is a rare X-linked dominant disorder within utero lethality in males. Affected patients have been reported tohave several different mutations in the PORCN gene on chromo-some Xp11.23. Dysplastic mesodermal and ectodermal tissuecauses clinical findings in the skin, skeleton, teeth, central nervoussystem, and eyes of affected patients. We describe the ophthalmo-logic findings in an 18-month-old boy with mosaicism of a novel mu-tation in PORCN.

Author affiliations: John A. Moran Eye Center, University of Utah, Salt Lake City, UtahSubmitted September 4, 2013.Revision accepted November 6, 2013.Correspondence: Marielle P. Young, MD, Moran Eye Center, University of Utah, 65

Mario Capecchi Drive, Salt Lake City, Utah 84132 (email: marielle.young@hsc.utah.edu).J AAPOS 2014;18:205-207.Copyright � 2014 by the American Association for Pediatric Ophthalmology and

Strabismus.1091-8531/$36.00http://dx.doi.org/10.1016/j.jaapos.2013.11.015

Journal of AAPOS

Case Report

An 18-month-old boy presented to John A. MoranEye Center, Salt Lake City, for evaluation of bilat-eral iris colobomas and left esotropia. He was previ-

ously seen by the Division of Medical Genetics anddiagnosed with Goltz-Gorlin syndrome (GGS), or focaldermal hypoplasia (FDH, MIM 305600), with clinical find-ings of syndactyly, split foot malformation, possible osteo-pathia striatum, nail dystrophy, cutis aplasia, dermalhypoplasia, simplified ears with underdevelopment of thesuperior helices, and ocular colobomas. He was also exam-ined by a cardiologist for pulmonary hypertension and atrialseptal defect.

DNA extracted from a peripheral blood sample wasamplified with polymerase chain reaction (PCR) forgenetic analysis. Exons 1-14 and flanking splice sites ofthe PORCN gene were amplified and sequenced bidirec-tionally with the published gene sequence until the muta-tion was found. Duplication of a single A nucleotide inexon 10 (c.956dupA) of the PORCN (PORCUPINE,DROSOPHILA, HOMOLOG OF) gene was identifiedin some, but not all, cells. This mutation causes a frame-shift and creates a premature stop codon at position 99 ofthe new reading frame and is predicted to cause loss ofnormal protein function through protein truncation ornonsense-mediated mRNA decay.

On ophthalmological examination, the patient was ableto fix and follow with each eye, although he would notmaintain fixation with the left eye. Binocular Teller visualacuity was 4.8 cy/cm. Pupils were minimally reactivesecondary to sizeable inferonasal iris colobomas. Assess-ment of his ocular alignment revealed a left esotropia of40D and a small amplitude, moderate frequency manifestnystagmus. Large, bilateral chorioretinal colobomas wereseen on dilated fundus examination.

Examination under anesthesia was performed. Intraoc-ular pressures were normal. Cycloplegic refraction re-vealed moderate, myopic astigmatism in each eye (righteye, �6.50 11.50 � 170; left eye, �5.00 11.00 � 170).The corneas were clear and measured 10 mm in diameterin the right eye and 9 mm in the left eye. Bilateral infero-nasal iris colobomas were present; no lens coloboma wasnoted. Dilated fundus examination of the right eye showeda large, inferior coloboma that bisected the macula and en-compassed amalformed optic disk that gave the appearanceof two optic nerve heads (Figure 1). The yellow appearancewithin the presumed fovea suggested the presence ofxanthophyll. There was a retinal flap tear near the ora ser-rata of the right eye. In the left eye, a larger, inferonasalchorioretinal coloboma involved the entire macula.Neither a central retinal artery nor a definite optic diskcould be discerned, but 3 regions of incompletely devel-oped optic disks were present (Figure 2). Small, hypopig-mented, patches were present supranasally, and areas(Figure 2) suggesting defects of the retinal pigment epithe-lium were seen temporally. A definitive ora serrata was

FIG 1. Inferonasal chorioretinal coloboma (right eye) that bisects themacula and encompasses a malformed optic nerve head appearing astwo optic disks; yellow pigmentary changes give the appearance ofxanthophyll.

FIG 2. Chorioretinal coloboma (left eye) with an abnormal optic disksuggesting 3 regions of underdeveloped optic nerve tissue without adiscernible central retinal artery; note small hypopigmented lesionssuperonasally that simulate small colobomas or areas of atrophy.

FIG 3. A, Fluorescein angiography showing an inferonasal retinal vesselfilling from the choroid at about 39 seconds. B, The choroid iscompletely filled at 43 seconds and supplies overlying retinal vessels;window defects are seen in the absence of overlying pigmented retina.

206 Young, Sawyer, and Hartnett Volume 18 Number 2 / April 2014

absent from 7 to 2 o’clock. Electroretinography wasnormal in the right eye and slighty subnormal in the lefteye. Flicker testing (30 Hz) was in the low–normal rangein each eye. Visual evoked potentials were subnormal inboth eyes and worse in the left eye.

Fundus photography and fluorescein angiography wereperformed (RetCam; Clarity Medical Systems, Pleasan-ton, CA). In the left eye a substantial delay in vascularfilling was noted; the choroidal vasculature began to fillat 26 seconds but only completely filled by 43 seconds.Three retinal vascular systems appeared to fill fromchoroidal vessels—an inferonasal vessel filling first atabout 39 seconds (Figure 3A) and the other vascular sys-tems by 43 seconds (Figure 3B). Complete filling of theretinal circulation did not occur until after 93 seconds.The right eye also appeared to have two separate vascularcomplexes associated with an abnormal divided optic disk.

Peripheral laser retinopexy was performed in the righteye around the flap tear.

Discussion

Focal dermal hypoplasia is a rare genetic disorder character-ized by a constellation of findings involving skin (atrophy andlinear pigmentation and herniation of fat through the dermaldefects occurring along the lines of Blaschko), skeletal (limbhypoplasia, syndactyly, polydactyly, oligodactyly), dental(hypoplastic teeth), central nervous system (developmentaldelay), and ophthalmologic (anophthalmia, coloboma,corneal clouding, strabismus) anomalies.1

Mutations in the PORCN have been described not onlyin FDH but also in cases of pentalogy of Cantrell andlimb-body wall complex.2 PORC proteins are thoughtto be involved in palmitoylation of Wnt signaling pro-teins, which play key roles in embryonic tissue develop-ment, particularly that of the dermis and skeleton.3 Wntsignaling involving the ligand Norrin is important in

retinal vascular development. Abnormalities in Norrincan lead to Norrie disease or X-linked familial exudativevitreoretinopathy.4

FDH is lethal in males, but males are affected in about10%-15% of FDH cases as a result of somatic mosaicismfor a post-zygotic mutation or X-chromosomal aberrations.5

Ophthalmologic pathology occurs in 40% of patientswith FDH and can include aniridia, strabismus, lens sub-luxation, microphthalmos, retinal pigment changes, opticatrophy, vitreous debris, ectropion, ptosis and nasolacrimalduct obstruction.6 There are reports of colobomatousretinal detachment and peripheral retinal nonperfusionwith subsequent neovascularization and hemorrhagerequiring retinal photocoagulation.7,8

We report a novel, somatic mutation in PORCN leadingto mosaicism in a young male patient and detail the clinicalphenotype, which suggests dramatic abnormalities in thedevelopment of the optic nerves and retinal vasculature.Such descriptions will not only provide insight intogenotype-phenotype correlations in FDH but will alsoadvance our understanding of Wnt signaling and its rolein embryogenesis.

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Volume 18 Number 2 / April 2014 Young, Sawyer, and Hartnett 207

Literature Search

PubMed was searched, most recently on August 22, 2013,for literature in English using the following search terms:Goltz syndrome, focal dermal hypoplasia, Wnt, and PORCN.

References

1. Goltz RW,Henderson RR,Hitch JM, Ott JE. Focal dermal hypoplasiasyndrome. A review of the literature and report of two cases. Arch Der-matol 1970;101:1-11.

2. Lombardi MP, Bulk S, Celli J, et al. Mutation update for the PORCNgene. Hum Mutat 2011;32:723-8.

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3. Clements SE. Importance of PORCN and Wnt signaling pathways inembryogenesis. Am J Med Genet 2009;149A:2050-51.

4. Parmalee NL, Kitajewski J. Wnt signaling in angiogenesis. Curr DrugTargets 2008;9:558-64.

5. Goltz RW. Focal dermal hypoplasia syndrome. An update. Arch Der-matol 1992;128:1108-11.

6. Thomas JV, Yoshizumi MO, Beyer CK, Craft JL, Albert DM. Ocularmanifestations of focal dermal hypoplasia syndrome. Arch Ophthalmol1977;95:1997-2001.

7. Prenner JL, Ciaccia S, Capone A Jr, Trese MT. Retinal detachment infocal dermal hypoplasia. Eur J Ophthalmol 2004;14:166-8.

8. DunlopAA,Harper JI,HamiltonAM.Retinalneovascularisation inGoltzsyndrome (focal dermal hypoplasia). Br J Ophthalmol 1999;83:1094.