Embryology History - Norman Gregg

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Introduction

Norman Gregg
Norman McAlister Gregg (1892-1966)

Norman McAlister Gregg (1892-1966) was a Sydney ophthalmologist who in 1941[1] identified the link between maternal rubella infection and developmental abnormalities (atypical congenital cataracts, congenital heart defects, infants small-for-gestational age) initially in his own practice. This had coincided with a rubella epidemic that occurred between 1940 to 1941.

"In the first half of the year, 1941, an unusual number of cases of congenital cataract made their appearance in Sydney. Cases of similar type, which appeared during the same period, have since been reported from widely separated parts of Australia. Their frequency, unusual characteristics and wide distribution warranted closer investigation, and this report is an attempt to bring to notice some of the more important features of what might almost be regarded as a mild epidemic.
I am indebted to many of my colleagues in New South Wales, Victoria and Queensland for particuars of very many of the cases reviewed. These, for the most part, conform very closely to the general features noted in my own series of cases on which the following description is based. The total number of cases included in this review is seventy-eight. My own cases total thirteen, and in addition I have seen seven others included in my colleagues’ lists."


Abnormal Development - Rubella Virus


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Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects


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Congenital cataract following German measles in the mother

Partial transcript of 1941 paper[1]


In the first half of the year, 1941, an unusual number of cases of congenital cataract made their appearance in Sydney. Cases of similar type, which appeared during the same period, have since been reported from widely separated parts of Australia. Their frequency, unusual characteristics and wide distribution warranted closer investigation, and this report is an attempt to bring to notice some of the more important features of what might almost be regarded as a mild epidemic.

I am indebted to many of my colleagues in New South Wales, Victoria and Queensland for particuars of very many of the cases reviewed. These, for the most part, conform very closely to the general features noted in my own series of cases on which the following description is based. The total number of cases included in this review is seventy-eight. My own cases total thirteen, and in addition I have seen seven others included in my colleagues’ lists.


General Description and Special Features

The first striking factor is that the cataracts, usually bilateral, were obvious from birth as dense white opacities completely occupying the pupillary area. Most of the babies were of small size, ill nourished and difficult to feed, with the result that many of them came under the care of the paediatrician before being seen by the ophthalmic surgeon. Many of them were found to be suffering from a congenital defect of the heart -a fact which, as will be explained later, has adversely affected full investigation of the condition of the lens and in some cases the treatment. The pupillary reaction to light was weak and sluggish; in some cases the irides had a somewhat atrophic appearance. This was more noticeable after mydriasis when the pupillary border appeared as a flat dark band seemingly devoid of any iris stroma.

Full mydriasis was difficult to obtain; in my experience it varied from one-half to three-quarters of the normal; moreover, an unusual number of the patients showed intolerance to atropine. In a large proportion of the cases one was forced to rely upon repeated instillations of homatropine to maintain the mydriasis.

Cataract

In the undilated condition of the pupil time opacities filled the entire area. After dilatation the opacities appeared densely white - sometimes quite pearly - in the central area with a small, apparently clear, zone between this and the pupillary border of the iris. Closer examination revealed in this zone a less dense opacity of smoky appearance, and outside this only a narrow ring through which a red reflex could be obtained.

The cataractous process seemed to have involved all but the outermost layers of the lens, and was considered to have begun early in time life of the embryo. Generally the cataract was symmetrically situated, but in a few cases it was somewhat excentric - in these there was some sparing of more of the fibres in the lower portion of the peripheral zone. Although the general appearance was such the same in all cases, two main types were noticed in the character of the cataract. In one the contrast between the larger dense white central area and the smaller cloudy more peripheral zone was very marked. In the other the density of the cataract was more uniform throughout and occupied an intermediate stage between that of the two portions of the other type. This distinction has been confirmed by the immediate results of operation. When needling was undertaken in cases of the first group, the dense white central portion was difficult to divide and sometimes separated off as a firm white disk. In others the whole lens seemed to be pushed away by the needle. Subsequent absorption in this group was delayed.

In the second type discussion was easier to per-form and absorption regular and uniformly progressive. In one case under my care both these types were present, the first type in the right eye and the second type in the left eye. In my opinion these variation is and those described by other observers are not essentially different from each other, and the apparent differences are due merely to a variation in intensity and duration of action of the same noxious factor.

The appearance of time cataract does not, in my opinion, exactly correspond to any of the large number of morphological types of congenital and developmental lenticular opacities that have been described. I do not wish to add to what Duke Elder (ref 1) has described as "time confusion which has arisen from the enthusiasm of various observers in the multiplication of types which differ but little in their essential pathology and vary only in their shape and position". I shall, therefore, merely describe the cataract as subtotal. Other descriptions by my colleagues in notes on their cases have been: central nuclear, complete, discoid, nuclear plus, anterior polar, dense central with riders,complete pearly, mature, and total lamellar. In sixteen cases of the whole series reviewed the cataract was unilateral.

Vision

In all cases the response to light was good; the babies appeared to follow readily any movement of the light stimulus.

Nystagmus

In time very young patients nystagmus was not noted, but in older babies or in cases in which treatment had to be delayed it was present. The movements were of a coarse, jerky, purposeless nature rather than a true nystagmus. It was a searching movement of the eyeballs and indicated the absence of any development of fixation. In my own cases it was always present if treatment had been delayed beyond the age of three months. In one case, in which time parents deferred operation in order to try some other form of treatment of which they had been informed, it developed before they consented to operation. In another case it developed after operation during the process of absorption. This development during the waiting period before operation has been noticed by other observers.

Variations

One case in my series was particularly interesting. The baby was referred to me at the age of three weeks with a diagnosis of bilateral keratitis. The cornea were quite white at birth and both parents had been subjected to a Wassermann test with negative results. At examination I noted a peculiar corneal haze, denser in the centre than in the periphery. The iris was just visible through this haze in the peripheral zone. The tension was normal and there was no inflammation. I advised reexamination under anaesthesia. This was done two weeks later. By this time the cornea had cleared and the typical white cataracts were seen in the pupillary areas. This baby subsequently became very il and it was only a few weeks ago that I was able to operate. At operation mydriasis was fuller than usual in these cases and the cataracts were the largest observed in this series.

Two other cases with similar corneal involvement have been noted- namely, by A. Odillo Maher and H.E.Robinson. Involvement was unilateral in Maher's and bilateral in Robinson's case. In these cases there had apparently been some temporary interference with the nutrition of the cornea. Maher's case is also interesting in that the mother developed cataract during pregnancy at the age of twenty-seven. This is the only instance throughout the series of any familial history of cataract.

In another case, reported by S. R. Gerstmain, there was "bilateral subluxation of the lenses, mature cataracts, accompanied by arachnodactyly and large fontanelle. Hip regions appeared normal."

Other complications reported have been cleft palate, one; congenital stenosis of naso-lachrymal (duct, three; calcaneus varus, one; although it is not certain whether these are above the average incidence in any group of infants of similar numbers.

Monocular Cases

The monocular cases merit special consideration. Sixteen of these have been reported, and in ten of them definite microphthalmia has been described.

In one of my cases-there were three in all-tlhe cataract was noted by the motlher only when the child was seven weeks old, though she stated that it may have been present before that date. The affected eye was definitely microplhthalmic, and examination of the other eye under mydriasis reve.lled a large pale area witlh some scattered pigmentation in the lower half of the fundus suggestive of a coloboma.

In another case the mother gave a history that both eyes were said to have had conjunctivitis at birth. This inflammation, she stated, cleared up under treatment in three weeks, and then two weeks later she noticed a white mass in the left pupil. Conceding the accuracy of these histories, I haven no doubt that the cataracts were present at birth in the central portion of the lens and that it was the final opacification of the more peripheral fibres. which in ad1e them apparent. In all other cases the cataracts have been apparent from birth.


Reporting her case of left-sided monocular cataract, Dr. Aileen Mitchell wrote:

No difference was noticed in the size of the eyes when the child was seveln weeks old; when the child was aged four months there was microphthalmia of the left eye. The mother said the eye had got small. Diameter of the right cornea was about 11 millimetres, of the left cornea 85 millimetres. Nystagmus, which was not present at the first examination, had developed and was coarse in nature with roving movement of the eyeballs. The fundus of the right eye appeared pale, and some scattered irregular shaped spots of pigment were observed.


L. Stanton Cook described one case, monocular central opacity of the lens, and writes: "It wouild appear that this cataract is a developmental defect rather than a toxic type."' As the baby also had the typical congenital defect of the heart, I feel that this is open to question.

Aetiology

Incidence of German Measles in this Series

In all but ten cases in this series the history of "Germanl measles" infection is present. In two of these ten cases the report is negative for measles; in one there was "history of kidney trouble"; in two others the report is definitely "history not asked for"; in the remaining five cases the report is"no history of measles"or"not known". It is interesting to note that the majority of these were cases occurring in 1940 or early in 1941 before the theory of a possible association between "Germaii measles" and the congenital cataracts was promulgated.

Geographical Distribution

Nature of Epidemic

Management

Operation

Prognosis

In the present state of our knowledge the only sure treatment available is that of prophylaxis. We must recognize and teach the potential dangers of such an epidemic or, I think, any other exanthem, and do all in our power to prevent its spread and particularly to guard the young married woman from the risk of infection.

If we agree that these cases are the result of infection of the mother by "German measles", what can we do to prevent a repetition of the tragedy in any future epidemic? Is the mass;of modern research into the causation of senile cataract going to be helpful by the discovery of some remedy which could be given to the mother to inhibit the formation of opacity in the developing lens of the embryo?


References

  1. 1.0 1.1 <pubmed>1879476</pubmed>| PMC2272051 | PDF

Reviews

Articles

GREGG NM. (1947). Congenital defects associated with maternal rubella. Aust Hosp , 14, 7-9. PMID: 18914301

Gregg NM. (1991). Congenital cataract following German measles in the mother. 1941. Aust N Z J Ophthalmol , 19, 267-76. PMID: 1789963

GREGG N. (1956). Congenital anomalies due to maternal infections especially in the early months of pregnancy. Trans Am Acad Ophthalmol Otolaryngol , 60, 199-205. PMID: 13324886

Hertzberg R. (1985). Congenital cataract following German measles in the mother. Abstracts from the publications of the late Sir Norman McAlister Gregg. Aust N Z J Ophthalmol , 13, 303-9. PMID: 3907670

Dunn PM. (2007). Perinatal lessons from the past: Sir Norman Gregg, ChM, MC, of Sydney (1892-1966) and rubella embryopathy. Arch. Dis. Child. Fetal Neonatal Ed. , 92, F513-4. PMID: 17951553 DOI.

Mackey DA. (2006). 2005 Gregg Lecture: Congenital cataract--from rubella to genetics. Clin. Experiment. Ophthalmol. , 34, 199-207. PMID: 16671898 DOI.

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Cite this page: Hill, M.A. (2019, September 23) Embryology Embryology History - Norman Gregg. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Embryology_History_-_Norman_Gregg

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