Clinical features and treatment of 12 cases with incontinentia pigmenti-associated retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Qiong , Ding Xiaoyan , Huang Sijian , Li Xiaoyu , Sun Limei , Li Songshan , Zhang Ting ,  Huang Li , Li Jiaqing

State Key Lab of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China;

Corresponding author：

Huang Li, Email: huangli@gzzoc.com

Keywords：

Incontinentia pigmenti; Retinal diseases; Disease attributes; IKBKG gene

DOI：

10.3760/cma.j.cn511434-20200826-00407

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Objective To observe and analyze the clinical features, treatment methods and efficacy of patients with retinopathy associated with incontinentia pigmenti (IP).Methods A retrospective case study. Twelve clinical confirmed IP patients (24 eyes) in Zhongshan Ophthalmic Center of Sun Yat-sen University from January 2015 to December 2018 were included in this study. The best corrected visual acuity and intraocular pressure examination were performed in patients (＞4 years old). All patients were examined on the anterior segment, vitreous body, and fundus under topical anesthesia or general anesthesia. Eight cases underwent genetic testing. Patients with active disease should be given anti-vascular endothelial growth factor (VEGF) drug treatment, retinal laser photocoagulation or vitrectomy, those without active disease should be observed. All patients were followed up for 1 to 3 months, with an average follow-up time of 18.7 months.Results All patients were all female, with an average age of 6.3±9.8 years old at the first ophthalmology visit. According to the recommendations of the pediatrician, 3 cases were actively screened for ophthalmology (referrals), with an average age of 0.4±0.5 years (median age: 2 months). A total of 9 cases were not recommended for referrals (non-referrals), including 3 cases of ophthalmology who were diagnosed for the first time due to visual impairment, and 6 cases of undiagnosed IP before the ophthalmology visit, the average age of their first visit was 8.2±10.8 years (medium age: 3 years old). The age of the first visit for non-referred patients was larger than that of referrals, and the difference was statistically significant (Z=−2.141, P=0.036). Among the 24 eyes of 12 cases, there were no obvious fundus abnormalities in 1 case or 2 eyes, 11 cases of IP-related retinopathy in 22 eyes (91.7%, 22/24), 8 cases of binocular asymmetry (66.7%, 8/12). There were active lesions on the fundus in 7 eyes (29.2%, 7/24). Patients underwent simple retinal laser photocoagulation and/or anti-VEGF drug therapy. During the follow-up, retinal neovascularization recurred in 1 eye. Among the 8 cases that underwent genetic testing, 3 cases (37.5%, 3/8) were deleted in exons 4-10 of the IKBKG gene.Conclusions IP is more common in women. IP-associated retinopathy is noted with early-onset, asymmetrical retinopathy, which is identified with retinal neovascularization and vitreous proliferation. Early detection and timely treatment are essential.

Citation： Wang Qiong, Ding Xiaoyan, Huang Sijian, Li Xiaoyu, Sun Limei, Li Songshan, Zhang Ting, Huang Li, Li Jiaqing. Clinical features and treatment of 12 cases with incontinentia pigmenti-associated retinopathy. Chinese Journal of Ocular Fundus Diseases, 2021, 37(4): 277-283. doi: 10.3760/cma.j.cn511434-20200826-00407 Copy

1.	Aradhya S, Woffendin H, Jakins T, et al. A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations[J]. Hum Mol Genet, 2001, 10(19): 2171-2179. DOI: 10.1093/hmg/10.19.2171.
2.	Minic S, Obradovic M, Kovacevic I, et al. Ocular anomalies in incontinentia pigmenti: literature review and meta-analysis[J]. Srp Arh Celok Lek, 2010, 138(7-8): 408-413. DOI: 10.2298/sarh1008408m.
3.	Fusco F, Bardaro T, Fimiani G, et al. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation[J]. Hum Mol Genet, 2004, 13(16): 1763-1773. DOI: 10.1093/hmg/ddh192.
4.	Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome)[J]. J Med Genet, 1993, 30(1): 53-59. DOI: 10.1136/jmg.30.1.53.
5.	Holmstrfm G, Thoren K. Ocular manifestations of incontinentia pigmenti[J]. Acta Ophthalmol Scand, 2000, 78(3): 348-353. DOI: 10.1034/j.1600-0420.2000.078003348.x.
6.	Peng J, Zhang Q, Long X, et al. Incontinentia pigmenti-associated ocular anomalies of paediatric incontinentia pigmenti patients in China[J]. Acta Ophthalmol, 2019, 97(3): 265-272. DOI: 10.1111/aos.13781.
7.	Song MJ, Chae JH, Park EA, et al. The common NF-kappaB essential modulator (NEMO) gene rearrangement in Korean patients with incontinentia pigmenti[J]. J Korean Med Sci, 2010, 25(10): 1513-1517. DOI: 10.3346/jkms.2010.25.10.1513.
8.	Hsiao PF, Lin SP, Chiang SS, et al. NEMO gene mutations in Chinese patients with incontinentia pigmenti[J]. J Formos Med Assoc, 2010, 109(3): 192-200. DOI: 10.1016/S0929-6646(10)60042-3.
9.	Phan TA, Wargon O, Turner AM. Incontinentia pigmenti case series: clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives[J]. Clin Exp Dermatol, 2005, 30(5): 474-480. DOI: 10.1111/j.1365-2230.2005.01848.x.
10.	Rahi J, Hungerford J. Early diagnosis of the retinopathy of incontinentia pigmenti: successful treatment by cryotherapy[J]. Br J Ophthalmol, 1990, 74(6): 377-379. DOI: 10.1136/bjo.74.6.377.
11.	Goldberg MF, Custis PH. Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome)[J]. Ophthalmology, 1993, 100(11): 1645-1654. DOI: 10.1016/s0161-6420(93)31422-3.
12.	Meuwissen ME, Mancini GM. Neurological findings in incontinentia pigmenti; a review[J]. Eur J Med Genet, 2012, 55(5): 323-331. DOI: 10.1016/j.ejmg.2012.04.007.
13.	Fusco F, Paciolla M, Conte MI, et al. Incontinentia pigmenti: report on data from 2000 to 2013[J/OL]. Orphanet J Rare Dis, 2014, 9: 93[2014-06-24]. https://pubmed.ncbi.nlm.nih.gov/24961275/. DOI: 10.1186/1750-1172-9-93.
14.	Carney RG. Incontinentia pigmenti. A world statistical analysis[J]. Arch Dermatol, 1976, 112(4): 535-542. DOI: 10.1001/archderm.1976.01630280059017.
15.	Francois J. Incontinentia pigmenti (Bloch-Sulzberger syndrome) and retinal changes[J]. Br J Ophthalmol, 1984, 68(1): 19-25. DOI: 10.1136/bjo.68.1.19.
16.	Yang Y, Guo Y, Ping Y, et al. Neonatal incontinentia pigmenti: six cases and a literature review[J]. Exp Ther Med, 2014, 8(6): 1797-1806. DOI: 10.3892/etm.2014.2011.
17.	O'Doherty M, Mc Creery K, Green AJ, et al. Incontinentia pigmenti--ophthalmological observation of a series of cases and review of the literature[J]. Br J Ophthalmol, 2011, 95(1): 11-16. DOI: 10.1136/bjo.2009.164434.
18.	Scheuerle AE, Ursini MV. Incontinentia pigmenti[DB/OL]. Seattle (WA): University of Washington, 2017[2017-12-21]. https://www.ncbi.nlm.nih.gov/books/NBK1472/.
19.	Schmitz ML, Mattioli I, Buss H, et al. NF-kappaB: a multifaceted transcription factor regulated at several levels[J]. Chembiochem, 2004, 5(10): 1348-1358. DOI: 10.1002/cbic.200400144.
20.	Greene-Roethke C. Incontinentia pigmenti: a summary review of this rare ectodermal dysplasia with neurologic manifestations, including treatment protocols[J/OL]. J Pediatr Health Care, 2017, 31(6): e45-e52[2017-09-01]. https://pubmed.ncbi.nlm.nih.gov/28870493/. DOI: 10.1016/j.pedhc.2017.07.003.
21.	Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti[J]. Am J Ophthalmol, 1990, 110(6): 701-702. DOI: 10.1016/s0002-9394(14)77071-0.
22.	Nguyen JK, Brady-Mccreery KM. Laser photocoagulation in preproliferative retinopathy of incontinentia pigmenti[J]. J AAPOS, 2001, 5(4): 258-259. DOI: 10.1067/mpa.2001.117098.
23.	Kychenthal A, Dorta P, Katz X. Zone Ⅰ retinopathy of prematurity: clinical characteristics and treatment outcomes[J]. Retina, 2006, 26(7 Suppl): S11-15. DOI: 10.1097/01.iae.0000244285.79004.e6.
24.	Ni Y, Huang X, Ruan L, et al. Intravitreal injection of ranibizumab in severe retinopathy of incontinentia pigmenti[J]. J AAPOS, 2018, 22(4): 325-327. DOI: 10.1016/j.jaapos.2018.01.008.
25.	Wald KJ, Mehta MC, Katsumi O, et al. Retinal detachments in incontinentia pigmenti[J]. Arch Ophthalmol, 1993, 111(5): 614-617. DOI: 10.1001/archopht.1993.01090050048026.

1. Aradhya S, Woffendin H, Jakins T, et al. A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations[J]. Hum Mol Genet, 2001, 10(19): 2171-2179. DOI: 10.1093/hmg/10.19.2171.
2. Minic S, Obradovic M, Kovacevic I, et al. Ocular anomalies in incontinentia pigmenti: literature review and meta-analysis[J]. Srp Arh Celok Lek, 2010, 138(7-8): 408-413. DOI: 10.2298/sarh1008408m.
3. Fusco F, Bardaro T, Fimiani G, et al. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation[J]. Hum Mol Genet, 2004, 13(16): 1763-1773. DOI: 10.1093/hmg/ddh192.
4. Landy SJ, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome)[J]. J Med Genet, 1993, 30(1): 53-59. DOI: 10.1136/jmg.30.1.53.
5. Holmstrfm G, Thoren K. Ocular manifestations of incontinentia pigmenti[J]. Acta Ophthalmol Scand, 2000, 78(3): 348-353. DOI: 10.1034/j.1600-0420.2000.078003348.x.
6. Peng J, Zhang Q, Long X, et al. Incontinentia pigmenti-associated ocular anomalies of paediatric incontinentia pigmenti patients in China[J]. Acta Ophthalmol, 2019, 97(3): 265-272. DOI: 10.1111/aos.13781.
7. Song MJ, Chae JH, Park EA, et al. The common NF-kappaB essential modulator (NEMO) gene rearrangement in Korean patients with incontinentia pigmenti[J]. J Korean Med Sci, 2010, 25(10): 1513-1517. DOI: 10.3346/jkms.2010.25.10.1513.
8. Hsiao PF, Lin SP, Chiang SS, et al. NEMO gene mutations in Chinese patients with incontinentia pigmenti[J]. J Formos Med Assoc, 2010, 109(3): 192-200. DOI: 10.1016/S0929-6646(10)60042-3.
9. Phan TA, Wargon O, Turner AM. Incontinentia pigmenti case series: clinical spectrum of incontinentia pigmenti in 53 female patients and their relatives[J]. Clin Exp Dermatol, 2005, 30(5): 474-480. DOI: 10.1111/j.1365-2230.2005.01848.x.
10. Rahi J, Hungerford J. Early diagnosis of the retinopathy of incontinentia pigmenti: successful treatment by cryotherapy[J]. Br J Ophthalmol, 1990, 74(6): 377-379. DOI: 10.1136/bjo.74.6.377.
11. Goldberg MF, Custis PH. Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome)[J]. Ophthalmology, 1993, 100(11): 1645-1654. DOI: 10.1016/s0161-6420(93)31422-3.
12. Meuwissen ME, Mancini GM. Neurological findings in incontinentia pigmenti; a review[J]. Eur J Med Genet, 2012, 55(5): 323-331. DOI: 10.1016/j.ejmg.2012.04.007.
13. Fusco F, Paciolla M, Conte MI, et al. Incontinentia pigmenti: report on data from 2000 to 2013[J/OL]. Orphanet J Rare Dis, 2014, 9: 93[2014-06-24]. https://pubmed.ncbi.nlm.nih.gov/24961275/. DOI: 10.1186/1750-1172-9-93.
14. Carney RG. Incontinentia pigmenti. A world statistical analysis[J]. Arch Dermatol, 1976, 112(4): 535-542. DOI: 10.1001/archderm.1976.01630280059017.
15. Francois J. Incontinentia pigmenti (Bloch-Sulzberger syndrome) and retinal changes[J]. Br J Ophthalmol, 1984, 68(1): 19-25. DOI: 10.1136/bjo.68.1.19.
16. Yang Y, Guo Y, Ping Y, et al. Neonatal incontinentia pigmenti: six cases and a literature review[J]. Exp Ther Med, 2014, 8(6): 1797-1806. DOI: 10.3892/etm.2014.2011.
17. O'Doherty M, Mc Creery K, Green AJ, et al. Incontinentia pigmenti--ophthalmological observation of a series of cases and review of the literature[J]. Br J Ophthalmol, 2011, 95(1): 11-16. DOI: 10.1136/bjo.2009.164434.
18. Scheuerle AE, Ursini MV. Incontinentia pigmenti[DB/OL]. Seattle (WA): University of Washington, 2017[2017-12-21]. https://www.ncbi.nlm.nih.gov/books/NBK1472/.
19. Schmitz ML, Mattioli I, Buss H, et al. NF-kappaB: a multifaceted transcription factor regulated at several levels[J]. Chembiochem, 2004, 5(10): 1348-1358. DOI: 10.1002/cbic.200400144.
20. Greene-Roethke C. Incontinentia pigmenti: a summary review of this rare ectodermal dysplasia with neurologic manifestations, including treatment protocols[J/OL]. J Pediatr Health Care, 2017, 31(6): e45-e52[2017-09-01]. https://pubmed.ncbi.nlm.nih.gov/28870493/. DOI: 10.1016/j.pedhc.2017.07.003.
21. Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti[J]. Am J Ophthalmol, 1990, 110(6): 701-702. DOI: 10.1016/s0002-9394(14)77071-0.
22. Nguyen JK, Brady-Mccreery KM. Laser photocoagulation in preproliferative retinopathy of incontinentia pigmenti[J]. J AAPOS, 2001, 5(4): 258-259. DOI: 10.1067/mpa.2001.117098.
23. Kychenthal A, Dorta P, Katz X. Zone Ⅰ retinopathy of prematurity: clinical characteristics and treatment outcomes[J]. Retina, 2006, 26(7 Suppl): S11-15. DOI: 10.1097/01.iae.0000244285.79004.e6.
24. Ni Y, Huang X, Ruan L, et al. Intravitreal injection of ranibizumab in severe retinopathy of incontinentia pigmenti[J]. J AAPOS, 2018, 22(4): 325-327. DOI: 10.1016/j.jaapos.2018.01.008.
25. Wald KJ, Mehta MC, Katsumi O, et al. Retinal detachments in incontinentia pigmenti[J]. Arch Ophthalmol, 1993, 111(5): 614-617. DOI: 10.1001/archopht.1993.01090050048026.

Chinese Journal of Ocular Fundus Diseases

Clinical features and treatment of 12 cases with incontinentia pigmenti-associated retinopathy

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