La tunisie Medicale - 2021 ; Vol 99 ( n°02 ) : 302-305
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Nous rapportons l’observation d’une fille ayant un syndrome de Turner avec une dystrophie rétinienne de type cônes-bâtonnets liée à une mutation dans le gène ABCA4.
Il s’agit d’une fille de 12 ans adressée pour baisse progressive de l’acuité visuelle associée à une héméralopie et à un retard statural. Nous avons effectué une étude clinique, un caryotype du sang périphérique et une analyse moléculaire. L’ADN a été adressé pour séquençage haut débit et les variants localisés dans les régions homozygotes ont été validées par séquençage Sanger.
L’examen du fond d’oeil a révélé une dystrophie rétinienne de type cônes-bâtonnets. L’examen général a montré une coarctation de l’aorte et un utérus infantile. Le caryotype du sang périphérique a révélé une monosomie 45X. le séquençage moléculaire a montré une mutation homozygote c.[885delC];[885delC] dans le gène ABCA4 et a exclu les mutations dans RPGR et dans ODF15.
Conclusions :
Le syndrome de Turner peut s’associer à diverses manifestations oculaires. Cependant, dans ce cas nous postulons l’hypothèse d’une association rare entre une monosomie X ayant occasionné un syndrome de Turner et d’une dystrophie rétinienne par mutation dans ABCA4.

Mots Clés

Turner syndrome results from chromosomal aberration that consists of the absence of the X chromosome. Its incidence is estimated to be 1/2000 to 1/3000 among live births in females [1,2]. Clinically, this syndrome is characterized by a female phenotype with short stature and ovarian dysgenesis. Several ocular disorders are associated with Turner syndrome including amblyopia, strabismus, ametropia, ptosis, nystagmus, hypertelorism, antimongoloid palpebral fissures, red-green deficiency, congenital glaucoma and blue sclera [3–6].
We report the phenotypic characteristics and genetic results in a 12-year-old female with Turner syndrome.
Case presentation:
We report the case of a 12-year-old female who was admitted to the B Department Hédi Raies institut of Ophtalmology in Tunis, Tunisia suffering from progressive visual loss and poor night vision. She did not report any pathological or ophthalmological history in the family, nor parental consanguinity. The general examination was normal, except for a short stature (-3 SD).  A complete ophthalmological evaluation was performed as well as fundus photography; fundus autofluorescence (FAF) (Heidelberg Spectralis; Heidelberg-Engineering, Heidelberg, Germany); optical coherence tomography (OCT) (Swept source DRI OCT-A Triton®, Topcon, Tokyo, Japan) and full-field electroretinogram (ERG) (Métrovision, France).  The best corrected visual acuity was 1/20 in both eyes. Anterior segment and intraocular pressure were normal. The eye fundus examination showed pallor of the optic disc, attenuated retinal vessels, paravascular bone spiculed pigmentations and an epimacular membrane (Figure 1 A and B). FAF showed paravascular and macular heterogeneous hypoautofluorescence (Figure 1 C and D). The OCT confirmed the presence of membrane and showed diffuse alteration of ellipsoid zone (Figure 1 E and F ). Additionally, full-field ERG showed decreased photopic and scotopic responses, attesting the damage of both cones and rods (Figure 2). In light of this clinical presentation, CRD was suspected and the patient was referred to Charles Nicolle hospital hereditary diseases department for genetic analysis.
The karyotype of peripheral blood showed monosomy 45,X confirming the diagnosis of Turner syndrome (Figure 3). Cardiovascular examination revealed aortic coarctation. Pelvic ultrasound showed an infantile uterus and the ovaries were not visible.  
Whole exome sequencing analysis identified a known ABCA4 deletion (c.885delC), resulting in a frameshift followed by a premature stop codon at position p.L296Cfs*4. This mutation was homozygous in the affected child and heterozygous in the unaffected mother. In addition, we excluded the presence of mutations in RPGR and ORF15 .
Turner syndrome is one of the most frequent sex chromosome aberrations [7] and  it is caused by the only viable monosomy, that of X chromosome.  To our knowledge, four cases of Turner syndrome with retinitis pigmentosa have been previously reported in the literature, however, three of these were presented without molecular genetic confirmation [8]. The fourth case was that of a 28-year-old patient in which the genetic analysis showed a novel mutation in the RPGR [8].
Our patient is a 12-year-old female diagnosed with CRD whose karyotype analysis revealed a homogeneous X monosomy. The identification of X-linked mutation was expected, however, the molecular genetic analysis uncovered a rare variant in ABCA4 (c.885delC, p.L296Cfs*4). The deletion (c.885delC) discovered in our patient is predicted to cause a frameshift at p.296 followed by a premature stop at p.299, generating a truncated ABCA4 protein [9]. This rare variant has been previously described in a patient with autosomal recessive Stargardt disease. However, the phenotype of our patient was different as ERG revealed severe cone and rod involvement. To our knowledge, this is the first reported case of CRD due to ABCA4 mutation in a patient with Turner syndrome.

Figure 1. Fundus photo, autofluorescence and OCT. CRD (A, B) with heterogeneous diffuse hypo autofluorescence (C, D). Alteration of ellipsoid zone and diffuse retinal atrophy (E, F).
Figure 2. Full field ERG.  Decreased scotopic (A), photopic (B) and flicker (C) responses
Figure 3. Karyotype. monosomy 45,X

  1. References 1. Jacobs PA, Browne C, Gregson N, Joyce C, White H. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet. 1992;29(2):103‑8. 2. Stochholm K, Juul S, Juel K, Naeraa RW, Hojbjerg Gravholt C. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006;91(10):3897‑902. 3. Chrousos GA, Ross JL, Chrousos G, et al. Ocular findings in Turner syndrome: a prospective study. Ophthalmology. 1984;91(8):926‑8. 4. Raab EL. Discussion on Turner’s syndrome. Am Orthopt J. 1971;21:56‑7. 5. Masters MC. Eyes and the Turner syndrome: a nationwide survey. Br Orthopt J. 1990;47:6‑17. 6. Denniston AKO, Butler L. Ophthalmic features of Turner’s syndrome. Eye. 2004;18(7):680. 7. Zhou Q, Yao F, Wang F, Li H, Chen R, Sui R. A heterozygous mutation in rpgr associated with X‐linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45, x/46, xx). Am J Med Genet A. 2018;176(1):214‑8. 8. Cordier J, Tridon P, Reny A. Turner’s syndrome and retinitis pigmentose. J Genet Hum. 1966;15:Suppl: 105-8. 9. Lin B, Cai X-B, Zheng Z-L, et al. Clinical and genetic analyses reveal novel pathogenic ABCA4 mutations in Stargardt disease families. Sci Rep. 2016;6:35414.
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