© Borgis - New Medicine 3/1999, s. 46-47
Teresa Oleniacz1, Hanna Dmeńska2
Upper and lower chronic respiratory tract infections in patients with retinitis pigmentosa (RP)
1 Audiology, Phoniatry and Laryngology Dept.
Head: Barbara Bułat, M.D.
2 Lung Physiology Dept. of The Memorial Institute of Child Health Centre, Warsaw
Head: Prof. Piotr Gutkowski, M.D.
Summary
Retinitis pigmentosa (RP) is a term for a heterogeneous group of hereditary retinal disorders characterised by progressive night blindness, loss of peripheral visual field and often by complete functional blindness by 40 to 50 years of age. Photoreceptor ultrastuctural studies of retinas in RP patients suggest that a defect of the connecting cilium of rods and cones could lead to the degeneration of these cells. It has been suggested that in RP patients motile cilia are also structurally defective. In this paper the cases of three brothers with X chromosome-linked RP and chronic upper and lower respiratory tract infections due to motile cilia structure disorders are presented.
RP defines a clinically and genetically heterogeneous group of congenital retinal diseases characterised by progressive photoreceptor and pigmentary retina epithelium degeneration. RP symptoms are night blindness, accommodation disorders, loss of the peripheral visual field, reduction of visual sharpness and even complete blindness by 4050 years of age. The disorders are always bilateral and of a progressive character. Ophthalmology examination shows the visual field reduced to 10°, reduction in visual sharpness, characteristic pigmentary changes on the eyeground, and electroretinography changes (lack or essential reduction of scotop and photop retinal response).
RP is inherited autosomally - in arecessive or dominant way or Xchromosome linked. Its incidence depends on the ethnic group and is 1:3500 to 1:4000. RP might be observed as an isolated form or as an element of syndromes including Usher, Laurence-Moon-Biedl, and Cockayene.
Photoreceptor ultrastructure studies in RP patients show that the basis of retinal degeneration is a disorder of the rods and cones connecting cilium (2, 6). The cilium connects the external segment containing the photosensitive pigment and the internal segment with cell organelles. The cilium structure is similar to the basal part of motile cilia; it is composed of nine microtubular doublets without central microtubules. There is also a lack of dynein arms and radial spokes (2). There is evidence that in RP cases there are ultrastructure disorders of both respiratory cilia and spermatozoon axoneme (1, 5, 7). Genetic studies show that RP depends on mutations of at least 7 genes; four of them are responsible for phototransduction protein cascade, two for the structure proteins of the external photoreceptor segment, and one for myosin VII formation (the deficit is observed in Usher´s syndrome type I). X-linked RP is clinically the most severe form and its incidence is 6 - 22% of all RP patients.
On the X chromosome are two specific loci for RP: RP2 located in the Xp 11.2 - p11.4 region and RP3 in the Xp 11.4 - p21.1 region. The loci are recessively expressed (4, 9). Recent publications describe new X chromosome RP loci expressed dominantly (7).
Case report
Three brothers - twins BU and D.U. born 31.07.81 and P.U. born 26.06.85 suffer from RP and chronic upper and lower respiratory tract infections. Similar symptoms are present in their uncle (mother´s brother). Females in the family (patient´s mother, her mother and her brother´s daughter) suffer from RP with a bilateral lack of eye pigment, visual field limitation to 10 -40o, decrease by 30-40% in photop and scotop responses in electroretinogrammes, and a lack of pigmentary changes on the eyeground.
A pedigree analysis performed by Dr M. Krawczyński from the Dept. of Medical Genetics in the Medical University in Poznań, suggests that there is in that family an X chromosome linked, dominant inheritance with mild expression in heterozygotic women.
In the three brothers´ RP was diagnosed in 1992, and in 1995 they underwent right lung middle lobe resection due to lung fibrosis and bronchiectasis. Now, they present perennial symptoms as a productive cough, and decreased nasal patency with muco-purulent secretion. The youngest brother suffers from ahearing loss.
A chest X-ray of P.U. has shown supradiaphragmatic fibrotic changes suggesting bronchiectasis, for BU and D.U. It was a normal chest x-ray. Pulmonary function testing in all of them showed increased airway resistance and reduced flow within peripheral airways.
Computed tomography showed great polypoid mucosal thickening in the paranasal sinuses with malformation of one (PU) or both (BU) frontal sinuses. Hearing loss due to otitis media with effusion was observed in one brother (PU). After 60 min. in the saccharine test no taste was noticed.
Respiratory epithelium histopathology (from lower nasal concha) showed no cilia but only microvilli. BU and DU showed asthenozoospermia. The observations are in accordance with other authors´ descriptions (3).
It has been decided to analyse the spermatozoon axoneme ultrastructure (the result is not available yet) and to repeat respiratory epithelium histopathology in order to define the axoneme structure defect.
Discussion
The RP family is one of the first described in the literature with an X-linke dominant inheritance (12). Further genetic studies might discover a new RP locus for the X chromosome. Chronic respiratory infection due to cilia dysfunction in RP patients is an unusual clinical manifestation of the syndrome.
Piśmiennictwo
1. Arden G.B., Fox B.: Increased incidence of abnormal nasal cilia in patients with retinitis pigmentosa. Nature 1979, 279:534-536. 2. Barrong S.D. et al.: Ultrastucture of connecting cilia in different forms of retinitis pigmentosa. Arch. Ophtalmol., 1992, 110:706-710. 3.Connor W.E. et al.: Sperm abnormalities in retinitis pigmentosa. Invest. Ophtalmol. Vis. Sci., 1997, 38:2619-28. 4. Fishman G.A. et al.: X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60. Ophtalmology 1998, 105:2286-96. 5.Fox B. et al.: Variations in the ultrastructure of human nasal cilia including abnormalities found in retinitis pigmentosa. J. Clin. Pathol., 1980, 33:327-335. 6. Hunter D.G. et al.: Abnormal axonemes in X-linked retinitis pigmentosa. Arch. Ophtalmol., 1988, 106:362-368. 7.Souied E. et al.: Severe manifestations in carrier females in x-linked retinitis pigmentosa. J. Med. Genetics 1997, 34:793-797. 8.Svedbergh B. et al.: Immotile cilia syndrome and the cilia of the eye. Albrecht von Graefes Arch. Klin. Ophtalmol., 1981, 215:265-272. 9. Welber R.G. et al.: X-linked retinitis pigmentosa associated with a 2-base pair insertion in codon 99 of the RP 3 gene RPGR. Arch. Ophtalmol., 1997, 115:1429-35.
