|Year : 1953 | Volume
| Issue : 1 | Page : 3-14
Tulsi Das, GC Gulati, MR Chaddah, RP Malhotra
Department of Ophthalmology, Medical College, Amritsar and Cardiology Clinic, V.J.. Hospital, Amritsar, India
|Date of Web Publication||15-May-2008|
Department of Ophthalmology, Medical College, Amritsar and Cardiology Clinic, V.J.. Hospital, Amritsar
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Das T, Gulati G C, Chaddah M R, Malhotra R P. Marfan's syndrome. Indian J Ophthalmol 1953;1:3-14
The idea which prompted us in presenting this study of two related families with several members suffering from Marfan's Syndrome is the association of ectopia lentil with all mesodermal defects and with no ectodermal abnormality. This aroused a strong suspicion that this anomaly was mesodermal and not ectodermal as stressed by Dr. Ida Mann.
Herein we include a study of two closely related families of 28 members 16 living and 12 dead. Out of the 16 living members 14 were examined and 8 of them had all the manifestations of Marfan's Syndrome. Four of the dead were described as tall and slim with defective vision and were said to have died at young ages, of heart failure: possibly they were cases belonging to this syndrome. Ectopia lentis as an isolated phenomenon was not seen in this group, although sporadic cases of ectopia lentis are seen now and then in our hospital. Two members of these families reported to the hospital for refractive errors. On routine examination they were found to be typical " Marfan's '' and were persuaded to bring all the members thus affected.
This present group of 8 cases with ectopia lentis as the main ocular manifestation had the following features in addition:-
(1) Arachnodactyly - long, thin and spidery fingers. (2) Unusually tall stature with slim bodies. (3) Cardio-vascular lesions, although only three complained of symptoms referable to the heart. (4) Abnormal spinal curvatures. (5) Prominent ears. (6) Decreased subcutaneous fat. (7) Underdeveloped musculature. (7) Relaxation of ligaments.
Other important features noticed in some of them but not in all were:
1. Divergent Squint 3 ( 37½,%)
2. Funnel-shaped chest 3 ( 37½% )
3. Dolicocephalic head 1(12½%)
4. Scoliosis 1(12½%)
5. Renal colic 2 (25 %)
6. Mental retardation 1 (12½)%
It is quite clear from the above facts that the families reported by us are rare as they represent the almost complete development of the features mentioned under Marfan's Syndrome. Marfan described this Syndrome in 1896,but his original description contained no reference to ocular anomalies.It was for Ormond; and Williams and Ormond14] to point out the frequent association of ectopia lentis and other ocular abnormalities with arachnodactyly while Archard was the first to describe familial incidence of the syndrome.
The following examinations were conducted:-
(1) External examination of the eye. (2) Complete fundus examination. (3) Measurement of the error of refraction. (4) Slit Lamp examination - in five cases only. (5) General physical examination. (6) Detailed cardiovascular examination (7) X-ray of the heart (8) Electro-cardiography. (9) Examination of blood for kahn's test.
Age and sex incidence :-- The youngest case examined was 5 years old While the eldest was 38. The cases were equally distributed among males and females. Transmitters were one brother and one sister. Each family has contributed four. The brother's family actually, consisted of eight (5 males and 3 females) out of whom four had this condition (2 females and 2 males ). "The sister had one son who had Marfan's syndrome and his family consisted of six children ( 4 males and 2 females ) out of whom three ( 2 females and 1 male ) had this condition. This suggests a proportionate preponderance in the females. The geneological tree is given in [Table - 1].
Heredity and Familial Incidence :-- It is generally agreed that Marfan's syndrome follows the Mendalian law and that it has a dominant character. In literature the incidence of Marfan's syndrome in the siblings is 30%, and in our series it is 28.6% . Considering the doubtful cases in addition, the percentage works out at 46.4%.
Local Examination : - The eyes appeared normal. Anterior chamber was deeper in the aphakic paint. In all cases the iris appeared lighter in colour and crypts were absent although radial streaks could he seen in some of them. Iris was tremulous opposite the aphakic part. The pupils were easily dilated although it was difficult to dilate these pupils fully. In six of them, in the pupillary area the lower margin of the lens could he seen easily through the undilated pupil. The two younger ones could he diagnosed as ectopia lentis only oil dilatation of the pupil. The dislocation was up and inwards in one and up and outwards in seven. Tension was normal in all. Fundus examination revealed no abnormality in any.
Refraction : - All of them had myopic astigmatism in the phakic amid hypermetropia in the aphakic part. Although myopia is supposed to be very high, almost 30D in some cases. in our series myopia was found to be not more than 10D except in one case which accepted -22D sph. The aphakic portion was comparatively larger and was retracted. The improvement though small in three cases. was appreciated by the patients . The distant vision varied between 6/36 and 6/24, and after correction of the aphakic part could he improved to 6/1 2. Four did not improve much. One could not be retracted due to want of co-operation ( mentally defective).
Slit-lamp examination: was carried out in five cases. AII of them had light brown irides which were tremulous in the lower half. The anterior surface was smooth and it did not show any crypts. [Figure - 2].In two cases there were two clefts in the outer two-third running concentric with tile pupillary margin. These clefts were deep and dark separating the collarette from the rest of the iris and dividing the portion peripheral to the collarette into two parts. The iris did not appear in one plane but showed terracing, the collarette being at the lowest plane. Radial streaks were present in a number of them. A lighter brown nodule could be seen in one case.
Anterior chamber was slightly deeper in the aphakic part in all the cases.
The lens was tremulous in all the cases. In one case its outer convex border could be seat with 5 to 6 shreds of zonular fibres. when the pupil was dilated. There was true light blown pigment on the broken shreds. In another case line, light brown pigment was present on the anterior surface of the lens. One case (D.D ) showed denser and rather opalescent nucleus with as clear zone of cortex which could be easily differentiated from the aphakic area by a thin and delicate line of demarcation.
General physical examination :-- All of them were tall, slim, frail with oblong faces. the vertical diameter being longer. They had typical long and spidery fingers. In all of them the distance between the extended upper extremities (as measured from the tip of one middle finger to that of the opposite one) was more than the height. In grown up adults the difference was as much as nine incites.
Cardiovascular aspects: Nine patients were examined by one of us (R.P.M.) it the cardiology Clinic of the V. J. Hospital.Amritsar.
They include the eight cases of complete Marfan's syndrome whose case historic, are given later, and the father of the B. L. family whose case history is not reported being an incomplete Marfan's.
All of them were examined radiologically and had their electro-cardiograms taken. One of them i.e. the head and the father of the B. L. Family had grossly damaged heart. He was tall and thin with arachnodactyly but he was free from the ocular Manifestations. He was a frank case of congestive cardiac failure. with auricular fibrillation, confirmed by the E.C.G.
The clinical cardio-vascular findings in our nine cases are tabulated as under:
Four out of nine patients had obvious cardiac symptoms and were already aware of the fact that their hearts were involved. Two patients had obvious enlargement of the size of the heart. In five cases auscultatory signs of the heart revealed a parasternal ,systolic murmur in the 2 nd , 3 rd , and 4 th , left intercostal spaces. One case showed a well marked systolic murmur in the mitral area which was well conducted and one case Showed triple rhythm in the mitral area. No case showed septal defect. patent ductus arteriosus or any other well classified congenital cardiac defect. History of a articular rheumatism was absent in all the cases and no clinical evidence of rheumatic heart disease i. e mitral or other involvement was found in any case. Elect rocardiographic investigations showed auricular fibrillation in one case. but the rest of of the cases showed normal tracings.
The main feature that strikes us in the cardiovascular aspects of these cases is the abnormality of the aorta in 8 out of 9 patients investigated. [Figure - 3],[Figure - 4]. This fact has been recently emphasised by Marvel and Genovese in their review of this subject Where they have reported the autopsy findings of 28 cases published till then. They report the medionecrosis of aorta in 39% of the cases. Incidence of Various necropsy findings in 28 cases arc reproduced in [Table - 3] for comparison.
Baer and Associates (1943) first reported cystic medionecrosis or congenital malformation of tunica media of the aorta in this disease. Erdheim called it Medionecrosis aortae-idiopathica cystica Baer and Taussig have reported cystic medionecrosis in the pulmonary artery in one of the 28 cases reported and Lindeboon and Westerveld-Bradon have reported similar changes in the external carotid artery.
it is significant to mention that out of 28 post-mortems reported by Marvel and Genovese fifteen showed aortic aneurysm. In our series eight of our nine cases showed abnormally shaped aorta and with the exception of one case all of them were below the age of 40. Only a further follow-up and autopsy will show as to how many of these will develop aneurysm of the aorta. Our main conclusion in the study of cardiovascular aspect of these cases is that the involvement of aorta is the most common significant finding in Marfan's syndrome.
| Case Histories|| |
1. B. L. aged 25, male. 6 ft. tall, thin, with oblong face and funnel shaped chest, long lingers. Bilateral ectopia lentis. observed through undilated pupil, dislocation up and out.
Vision R.E. 6/36; with +13D sph 1.5D cyl at 120 o 6/12.
L.F.. 6/36: with + 12D sph 6/12.
Fundus showed no abnormality. Tension 20 mm. ( Schiotz ) B. E.
Cardiovascular System : pulse 76, regular; B.P. 150/100.
Auscultation: systolic murmur over 2nd and 3rd left inter-costal spaces, disappearing on sitting up.
X-ray chest: tall aorta. A healed tubecular lesion seen in the supraclavicular part of the left lung.
2. R. L. aged 28, male, tall, thin, with oblong face and spidery lingers, funnel shaped chest: height 6 feet; distance between extended Upper extremities 6 feet 9 inches. Iris: light coloured and without crypts. Bilateral ectopia lentis, observable through undilated pupil, dislocation up and out.
Slit lamp examination revealed a lot of pigment on the anterior surface of the lens. Radial streaks on the iris could be seen but there were no crypts.
Vision 6 36 B.E. could not be improved.
Tension R. E. 22 mm.
L. E. 24 mm.
Cardio-vascular System: pulse 104, regular: B.P. 138/86.
Ausculatation: localised systolic murmur in 4th and 5th left intercostal spaces which persists on sitting up.
X-ray chest : tall aorta.
E.C.G. : rate 100, voltage normal. rhythm regular. Ventricular extra systoles in lead III. P wave normal; PR interval 0.16 second. QRS slurring in lead III. ST iso-electric. T wave normal.
3. S. D. aged 22, female, tall, long fingers and thin built. Bilateral ectopia lends, dislocation up and in, seen through undilated pupil. Divergent squint of 10°.
Vision R.E. (6/24: with + 10D sph 6/12.
L.E. 6/36: with + 11D sph 6/18.
Fundus: no abnormality.
Tension 20 mm. B.E.
Cardio-vascular system pulse 100. irregular. B. P. 170/100.
Auscultation: triple rhythm present, i.e. Systolic gallop rhythm. X-ray chest: tall aorta with some cardiac enlargement.
E.C.G.: rate 91, rhythm regular; voltage normal. P-wave normal P-R 0.15
second QRS slurring in L I, II and III. T wave positive in L I and IV, flat in L II. iso-electric in L III. Indicates myocardial damage.
4. S. K. aged 18, female, tall, with oblong face, long, thin and spidery fingers. Height 5 feet 2 inches. Distance between extended upper extremities 5 feet 6 ½ inches. Iris: light coloured and without crypts. Bilateral ectopia lentis, dislocation up and out seen through undilated pupil.
Slit lamp examination of the iris surface showed fine pits and it was demarcated into 3 zones on the lateral side: a few crypts could be seen, medial to the collarette.
Vision: B. E. 6/18 no improvement.
Tension : B.E. 20 min. ( Schiotz ).
Cardio-Vascular system: pulse 96. irregularly irregular, B.P. 150/100.
Auscultation: Very accentuated first sound in the mitral area With loud systolic murmur conducted to the back: murmur over third and fourth spaces and aortic area: pulmonary second sound loud, aortic second sound just audible.
X-ray Chest: heart normal. Old pleurisy on left side. Tall aorta.
E.C.G. : rate 108, rhythm regular, voltage normal: P wage normal: PR 0.15 second. QRS shows slurring in all the leads and left axis shift. ST iso-electric. T wave flat in all leads. Conclusion: Left axis shift with myocardial damage.
| D.D. Family|| |
1. D. D. aged 38, male, 5 feet 11 inches tall, oblong face, thin and long fingers; distance between extended upper extremities 6 feet 2 inches. Iris light coloured, radial steaks present but crypts could not be easily seen. Bilateral ectopia lentis, displacement up and out seen through undilated pupils. Both lenses showed opalescent nucleus With a clear zone of transparent cortex peripherally which could easily be differentiated from the aphakic area by a thin demarcation line.
Slit lamp examination showed no concentric folds or crypts on the right side but radial streaks were present. On the left side iris was darker and pigment deposit was seen deposited on shreds of the zonule.
Vision : B.E. 6 24 partial, could not be appreciably improved.
Fundus: nothing abnormal.
Tension :R.E. 21 mm.: L.E. 19 mm. ( Schiotz ).
Cardio-vascular system: pulse 90, regular: B.P. 148/86.
Auscultation: a soft systolic. murmur in 2nd and 3rd left intercostal spaces; murmur disappeared when patient was made to sit up; loud pulmonary second sound.
X-ray chest : long diameter of heart is at the top normal limit. Some resemblance to honeycomb appearance seen in the lower part of the left lung. Ascending aorta slightly displaced outwards with a prominent knuckle.
2. D. K. aged 13, female, tall and thin, oval face, spidery fingers. Bilateral ectopia lentis, dislocation up and out seen through undilated pupils.
Vision : R. E. 6/24 with + 11.0D sph 6/12.
L.E. 6/36 with + 11.0D sph 6/12.
Fundus: nothing abnormal.
Tension :B.E 18 mm. ( Schiotz ).
Cardio-vascular system: pulse 90, well marked sinus arrhythmia.B.P 108/60.
Auscultation: Well marked systolic murmur in second, third and fourth left intercostal spaces, best heard over third: pulmonary second sound accentuated.
X-ray Chest: aortic shadow unusually tall.
E.C.G. : nothing abnormal.
2. S. K. aged 12, female, tall for her age: thin oval face: spidery fingers. Height: 5 feet , ½inch; distance between extended upper extremities 5 feet 6 inches. Iris was lighter in colour and a small nodule 1 mm in diameter was present on its surface 2 mm. from pupillary margin at 7 o'clock position. Bilateral ectopia lentis seen after dilating pupil, dislocation up and out.
Slit lamp examination: no crypts could be seen and iris surface was demarcated into 3 zones on the lateral side.
Vision : B.E. 6/24 and j 5. no appreciable improvement.
Tension : B.E. 18 mm. ( Schiotz ).
Cardio-vascular system: pulse 86. well marked sinus arhythmia, B.P. 104/60.
Auscultation: soft systolic murmur over 2nd, 3rd and 4th left intercostal spaces, disappears on sitting up.
X-ray chest; unusually tall aorta with a prominent knuckle.
E.C.G.: nothing abnormal.
3. R. M. aged 5, male, thin and long lingers, oval face with dolicocephalic head: scoliosis; divergent squint of 10 o . Height: 3 feet 11½ inches; distance between extended upper extremities 4 feet 2½ inchs. Iris light coloured, normal pattern could be seen. Bilateral ectopia lentis; dislocation up and out seen after dilating the pupil. Mentally backward and non-cooperating.
Slit lamp examination: Iris surface was separated into two parts by a circular line of demarcation; radial streaks were present but no crypts could be seen.
Vision: Could not be recorded as patient was not cooperating.
Tension: B.E. 18 mm.
Fundus: nothing abnormal.
Cardio-vascular system: pulse 102, regular. B. P. 86/50.
Auscultation: no abnormality.
X-ray chest: Ascending aorta slightly pushed out with a prominent knuckle.
E. C. G. : normal.
| Comments|| |
A controversy still exists as to the genesis of ectopia lentis. The prevalent view is that it is due to a defect in the development of the suspensory ligament. It is implied therefore, that dislocation of the lens is secondary to the changes in tile Zonule of Zinn. It is an external manifestation of a hidden and unrevealed defect. The main discussion is whether the anomaly of the suspensory ligament itself is primary and therefore ectodermal or is a result of mesodermal defect which causes actual defect or delay in the development of the suspensor ligament. Considering the association of defective development of suspensory ligament with coloboma of the lens it is but natural to suppose that the suspensory ligament plays a primary role. What factors are really responsible for this is not yet clear. In coloboma of the lens persistence of the capsulo-pupillary vessels is proved, whereas in ectopia lentis they are said to have no role, as they disappear and degenerate at third month of intra-uterine life, just when suspensory ligament begins to develop. But the occasional presence of pupillary membrane, notches in the lens, corectopia. polycoria. etc., with ectopia lentis makes one feel that there is some mesodermal abnormality which hinders the proper growth of the suspensors ligament from tile ciliary body. As the anomaly is situated ill the lower half i.e. in the region of the faetal cleft along which all mesodermal tissues gain access to the interior of the eye, it is possible that this mesodermal tissue persists longer at this place. It is a known and proven fact that persistence of this mesodermal tissue produces imbalance of growth factors not only it the suspensory ligament but also it the other parts of the eye. This therefore appears to be the primary factor. With weakness of the lower paint of the suspensory ligament there may be an upward pull by the upper fibres of the ligament. This is understandable because of the stronger growth of the upper part of the zonule of zinn. The struggle of these zonule fibres gradually diminishes as one proceeds downwards towards the fetal fissure.
As the disease is hereditary and germinal. other anomalies are expected and somehow all of them are traceable to defective development of the mesodermal tissues. These deformities are spinal curvature, arachnodactyly. cardio vascular lesions, lighter colour of the iris, absence of crypts, etc. It is a very significant fact that no other ectodermal defect was noticed except for mental retardation in one case which may be just a coincidence. On the other hand in primary ectodermal defects of the lens such as lamellar cataract. the association of anomalies of brain and enamel of teeth point to the association of all ectodermal lesions. At the same time, working on the analogy of aniridia, considering it to be a primary ectodermal defect we find the association of other ectodermal anomalies in the tissues growing and differentiating at the same time i.e. at 70-80 mm . Stage. When ectoderm of the iris fails to develop, fovea and lens show defective development. Therefore association of small lens and undeveloped fovea ( nystagmus ) point to the whole defect being ectodermal which means that the biochemical factor responsible for these ectodermal defects was not localised to one particular spot. Similarly in ectopia lent is, this constant association of all mesodermal defects with it, point to its being primarily mesodermal (overgrowth or undue persistence). The persistence of abnormal mesodermal tissue in the irides of five cases on whom slit lamp examination was done (revealed through absence of crypts etc.) strongly supports our hypothesis that it is the undue persistence of mesodermal tissue which probably is responsible for ectopia lentis.
Ormond" believes that there is some hormonal toxin which produces biochemical effects but he does not try to put the blame on a primary ectodermal or mesodermal anomaly.
Prof. Ida Mann" however is of the opinion that the defects in the suspensory ligament may be primary and biochemical. She states that the mesodermal defect may be co-existing but stay not be the essential cause of the defect in the ectodermal tissue. She postulates that the defect of the genes may operate on both the mesodermal and ectodermal tissues growing at the time and thinks the anomaly to be genophytic.
Vogt blames the ciliary body for defective development (secretion) of the suspensory ligament. No defect could however be seen in the ciliary body and if a defect is there why should it be always localised in the lower part and secondly, the defect may be in the blood vessels which are again mesodermal.
Duke-Elder's' view, as he postulates some organic biochemical poison acting on embryonic mesoderm, lends support to our view.
| Summary|| |
1. :A report of two closely related families with almost complete Marfan's syndrome is presented.
2. The mesodermal origin of ectopia lentis is strongly supported by the association of all mesodermal defects without the association of any ectodermal anomaly, and the absence of crypts in the Iris with undue persistence of fibrous tissue.
3. Myopia was of moderate degree and not high as mentioned in literature except in one case.
4. Pupil dilated easily with mydriatic in all cases.
5. Dislocation of lens in most cases was up and out. The aphakic portion was larger than the phakic, thus all patients derived benefit from convex lenses i.e. correction of the aphakic portion.
6. Cardiovascular lesions were well advanced in must of them: aortic manifestations were the main clinical features.
| References|| |
Achard M.C "Arachnodactylie" Bull et mem Soc. Med. D'hop de paris 19, Oct 1902p.834-as quoted by Lutman & Nael".
Baer, R.W. Taussing H.B and Oppenheimer E.H."Congenital Aneurysmal Dilatation of the Aorta Associated with Arachnodactyly", Bull-Johns Hopkins Hosp.72,1943,p.309.
Bellows J.G "Cataract and Anomalies of the lens",1944,p,260. C.V.Mosby Co.St.Louis.
Duke-Elder, W.S."Text Book of Ophthalmology", 1938, Vol,2,p1351, C.V Mosby Company St.Louis.
Erdheim J."Medionecrosis Aorta Idiopathica",Virchows Arch,Path Anath,1929,p.254.
Lindeboom G.A and Westerveld Bradon E.R."Dilatation of the Aorta in Arachnodactyly", Cardiologia. 17,1950p.217.
Lloyd Ralph "Clinical Course of Ocular Complications of Arachnodactyly", Arch Ophth.40(November) 1948, p.558.
Lutman Frank C and Nael James. V"Inheritance of Arachnodactyly, Ectiopia Lentis and other Congenital Anomalies (Marfan's Syndrome) in the E.Family", Arch Ophth 419March) 1949,p.276.
Mann Ida 'Development Abnormalities of the eye", 1937, pp.353-357, Cambridge University Press, London.
Mann Ida. "The Development of the Human Eye", 1950, Grune, Strallon, New York.
Marfan A.B. " Un cas de deformation congentale des quatre members, plus prononcee aux extremities characterisee par I'allongement des os, Avec uncertain degree d'aminicissement". - Bull. Et mem Soc.Med d'hop de paris 13,feb 1896,220 'quoted by Lutman & Nael.
Marvel R.J and Genovese " CARDIOVASCULAR DISEASE IN Marfan's Syndrome" American Heart Journal 1951,p.814.
Ormond A.W."Etiology of arachnodactyly with special reference to ocular symptoms " Proc.Intern.Cong.Ophth.2,1929,645-as quoted by Lutman & Nael.
Ormond A.W. and Williams R.G "A case of arachnodactyly with special reference to ocular symptoms" Guy's Hosp.Rep.,47,Oct,1924,385-as quoted by Lutman & Nael".
Rados, R "Marfan's Syndrome", Arch.Ophth. 27, March 1942,477.
Walsh, Frank B. 'Clinical Neuro-ophthalmology", 1948, The Williams and Watkins Company Baltimore.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3]