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Simultaneous Presence of Macular Corneal Dystrophy and Retinitis Pigmentosa in Three Members of a Family.


Corneal dystrophies are a group of diverse bilateral genetic and non-inflammatory diseases limited to the cornea. Clinically, it is categorized into three groups; superficial corneal dystrophy, corneal stromal dystrophy, and posterior corneal dystrophy which are further subcategorized into other classes. Macular corneal dystrophy (MCD) is a subcategory of corneal stromal dystrophies. (1) Mutation in carbohydrate (N-acetylglucosamine6-O) sulfotransferase 6 (CHST6) gene is usually responsible for MCD. However, all MCD cases cannot be explained by mutations in CHST6 coding region, deletion or replacement in the upstream region, or mutations in splice sites resulting in loss of splicing signal. (2)

Retinitis pigmentosa (RP) is a disease with a variety of disorders. Some patients show symptoms of vision loss during childhood while some others live without any symptoms until their middle age. (3) Most cases present classical symptoms of difficulties with adapting to darkness and night blindness (nyctalopia) in old age and loss of vision in early adolescence. Following the disease progression, they lose their distant peripheral vision, tunnel vision, and finally central vision which usually occurs at the age of sixty. The reduction of ROD and CONE is similar in other types. Sometimes the decrease in CONE is greater than that in ROD which is then called cone-rod degeneration, a form of RP in which the loss of vision and defects in color vision are the predominant initial symptoms. (4)

Here, we present a case report study of a family with three children suffering from both MCD and RP diseases simultaneously. According to our search of databases, there has been no report regarding the co-occurrence of these diseases; hence, the present article is the first reported case on this topic.

Case Presentation

We present the case of a 9-member family that includes the parents (consanguineous marriage) and 7 children (2 girls and 5 boys). The parents had healthy eyes and among the children, only two had healthy vision. One male descendant had keratoconus while the other had MCD. Three children (two boys: 30 and 36-year-old man, one girl: 41 years old) showed the co-occurrence of both MCD and RP (figure 1). One of the patients, 36 years male, referred to the clinic with the complaint of difficulties in undertaking tasks at night or in dark places. His vision impairment had started from childhood but deteriorated over the past 10 years. Visual acuity of the patient was finger counting (CF) at 1.5 m and 1 m on the right and left eye, respectively. The use of eyeglasses had no effect on his vision. Written informed consent was obtained from all patients enrolled in this report.

MCD can be easily identified by clinical examination. Using a photoslit device, the patient's cornea with MCD is shown in figure 2. Multiple gray-white patches are distributed over the cornea and all layers involved with peripheral expansion can be observed with the same pattern in both eyes. Histopathological evaluation confirmed MCD in this patient (figure 3). The diagnosis of RP is also clinical. Dilated fundus examination clearly showed blood vessels attenuation, boney spicules, and waxy disc pallor; all of which confirmed RP in this patient (figure 4). Conventional treatments were employed for these patients. Keratoplasty was performed for MCD due to the intensity of the disease. Serological analysis was performed before surgery and the results demonstrated that all patients were negative for infectious diseases such as syphilis. Since there is no effective treatment, supplementary drugs were used for RP.


The present case report describes a 9-member family in which 3 out of 5 children suffered from MCD and RP. Although Crawford (5) had reported a case of concurrent granular corneal dystrophy (GCD) and RP with autosomal dominant inheritance in a 58-year-old Korean woman, we present the first report of simultaneous MCD and RP. MCD is inherited as recessive autosomal and it appears to be caused by abnormal structures of creatinine sulfate, which is triggered by a mutation in CHST6 gene. (6) The most common disorder is mediated by missense or nonsense single nucleotide polymorphisms (SNPs) in CHST6, which causes a change in a protected amino acid. Heterozygous mutation in the exon 3 of CHST6 gene has been detected in most families, almost all of them are associated with another heterozygous mutation in the CHST6 coding region on the other chromosome. (7) Other mutations causing MCD relate to the insertion or deletion of nucleotides in the CHST6 coding region, which alters frame-shift and also a few upstream deletion or substitution between CHST5 and CHST6. (8)

RP is a non-age-related disease and the symptoms can manifest in all ages. (9) The inheritance of the disease has so far been reported as autosomal recessive and dominant, and X-linked forms. Studies have shown that there are at least 85 loci in mutagens that cause the disorder (mutation in 56 genes causes non-syndromic RP, mutation in 12 genes causes Usher syndrome, and mutation in 17 genes cause Bardet-Biedl syndrome). In general, mutations in RHO (rhodopsin), USH2A, and RPGR genes lead to 30% of all cases of RP. Of other genes that can cause autosomal dominant RP include RP1 [8q12.1], PRPF3 (pre-MRNA processing factor 3) [1q21.2], PRPF8 [17p13.3], and PRPF31 [19q13.42] have been identified to contribute 5.5%, 4%, 2%, and 5%, respectively. Mutations in genes such as RP1L1 [8q23.1], RLBP1 (retinaldehyde binding protein 1) [15q26.1], CRB1 (crumbs family member 1) [1q31.3], ABCA4 (ATP-binding cassette subfamily A member 4) [1p22.1], RPE65 (retinal pigment epithelium-specific protein 65kDa) [1p31.2], and CNGB1 (cyclic nucleotide gated channel beta 1) [16q21] also share 1%, 1%, 6.5%, 2%, and 4%, respectively, in autosomal recessive inheritance. (9)

As can be seen in figure 1, the inheritance of both diseases is recessive (lack of parental illness) and autosomal (not X-linked due to the occurrence of the disease in one of the girls and lack of paternal illness for any of the diseases). Considering that the parents' werecousin marriage, the chance to inherit the defective gene from ancestors increases. However, in order to clarify and exclude the possibility of de novo dominant mutation in parents' germ cells, further studies are required on both parents. According to the location of CHAT6 gene and also the major role of CNGB1 gene (with the frequency of 4% in patients with RP) located in 16q21 to develop RP, this gene can be used as one of the first candidates for genetic investigation with the chance of discovering a translocation mutation in these genes. On the other hand, Davidson et al. (10) identified a homozygous frame-shifting mutation, c.601delG, p.Lys203Argfs*28, in RP1L1 in a consanguineous family with RP, while various mutations in this gene had been reported to be associated with occult macular dystrophy (OCMD). As a result of this case report, RP1L1 can be the second candidate for genetic investigations. Considering different mutations in CHST6 gene on the 16q23 region to create MCD as well as the role of different mutations (mutation in more than 40 genes) to generate RP disease, it is important to investigate both diseases genetically by molecular methods to discover the reason behind the association of these two diseases.

Conflict of Interest: None declared.


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(2.) Klintworth GK. Advances in the molecular genetics of corneal dystrophies. Am J Ophthalmol. 1999;128:747-54. doi: 10.1016/S0002-9394(99)00358-X. PubMed PMID: 10612512.

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(5.) Crawford C. Retinitis pigmentosa and granular dystrophy: A rare and unique combination in one patient. Binocul Vis Strabolog Q Simms Romano. 2013;28:36-8. PubMed PMID: 23521034.

(6.) Aldave AJ, Yellore VS, Thonar EJ, Udar N, Warren JF, Yoon MK, et al. Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. Am J Ophthalmol. 2004;137:465-73. doi: 10.1016/j.ajo.2003.09.036. PubMed PMID: 15013869.

(7.) Vance JM, Jonasson F, Lennon F, Sarrica J, Damji KF, Stauffer J, et al. Linkage of a gene for macular corneal dystrophy to chromosome 16. Am J Hum Genet. 1996;58:757-62. PubMed PMID: 8644739; PubMed Central PMCID: PMCPMC1914688.

(8.) Klintworth GK, Smith CF, Bowling BL. CHST6 mutations in North American subjects with macular corneal dystrophy: A comprehensive molecular genetic review. Mol Vis. 2006;12:159-76. PubMed PMID: 16568029.

(9.) Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795-809. doi: 10.1016/S0140-6736(06)69740-7. PubMed PMID: 17113430.

(10.) Davidson AE, Sergouniotis PI, Mackay DS, Wright GA, Waseem NH, Michaelides M, et al. RP1L1 variants are associated with a spectrum of inherited retinal diseases including retinitis pigmentosa and occult macular dystrophy. Hum Mutat. 2013;34:506-14. doi: 10.1002/humu.22264. PubMed PMID: 23281133.

Farhad Nejat (1), MD;

Hossein Aghamollaei (2), PhD;

Shiva Pirhadi (3), PhD;

Khosrow Jadidi (4), MD;

Mohammad Amin Nejat (3), MS

(1) Vision Health Research Center, Tehran, Iran;

(2) Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;

(3) Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran;

(4) Department of Ophthalmology, Baqiyatallah University of Medical Sciences, Tehran, Iran


Khosrow Jadidi, MD;

Department of Ophthalmology, Baqiyatallah University of Medical

Sciences, Molasadra St., Tehran, Iran

Tel/Fax: +98 21 88196862


Received: 01 August 2016

Revised: 05 December 2016

Accepted: 11 December 2016

What's Known

* Macular corneal dystrophy (MCD) and retinitis pigmentosa (RP) are two separate eye diseases.

* There is no report on simultaneous presence of MCD and RP in a patient.

What's New

* Using clinical investigation, we report on three familial patients suffering from both MCD and RP simultaneously.

* Based on the family tree, it seems that the inheritance of both diseases is autosomal recessive.
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Title Annotation:Case Report
Author:Nejat, Farhad; Aghamollaei, Hossein; Pirhadi, Shiva; Jadidi, Khosrow; Nejat, Mohammad Amin
Publication:Iranian Journal of Medical Sciences
Article Type:Report
Date:Mar 1, 2018
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