Noonan syndrome

(CHEST 2001; 120.1368-1371)

Key words: earliest illustration; historical article; hypoplastic left heart syndrome

The term hypoplastic left-heart syndrome was first proposed by Noonan and Nadas (1) in 1958 and comprises a continuum of congenital cardiac anomalies characterized by underdevelopment of the aorta, aortic valve, left ventricle, mitral valve, and left atrium. The first published cases of aortic atresia were reported by Romberg (2) in 1846 and Canton (3) in 1849, and are more or less restricted to brief pathologic and anatomic descriptions. Neither pathophysiologic nor pathogenetic aspects were discussed. The account of Dr. Bardeleben, (4) written in 1851, was probably the first complete description of the clinical features, the pathologic-anatomic characteristics, and the pathophysiology of the hypoplastic left-heart syndrome. It includes an illustration of this malformation, a hypothesis on the etiology, and reflections on the symptoms. This historical publication documents the correct understanding of the circulation in this disorder, realizing that survival depends on a patent ductus arteriosus. Also, a differentiated theory on the development of cyanosis is provided. Pathogenetically, Dr. Bardeleben attributed aortic atresia not to a simple arrest of normal development, but to a pathologic process developing during intrauterine life. The precision and the clarity of the description and figures is striking. This account given by Dr. Bardeleben remains entirely valid even today. The following literal translation of the original manuscript gives the reader a sense of the original and gives credit to this early, superb, as yet unknown description (in the international literature) of a congenital heart disease.

OBLITERATION OF THE LEFT OSTIUM ARTERIOSUM IN THE HEART OF A HALF-YEAR OLD INFANT

Examined and Described by Professor Bardeleben

By the kindness of Professor Wernher, I have had the opportunity of examining a heart specimen cum annexis that had been sent to him as the director of the pathological collection at Giessen by a general practitioner and that deserves particular description because of its extremely peculiar malformation. At the beginning, I mention the writing of the practitioner containing the postmortem account, as far as it is of interest here, and also the account of the observations made on the infant during life in order to refer to them later. Unfortunately, a lot can be missed.

ACCOUNT OF THE PRACTITIONER'S POSTMORTEM FINDINGS

On opening the abdomen, the liver occupied the largest part of the abdominal cavity and was filled with dark blood. Otherwise, nothing abnormal was found in the abdominal cavity. After opening the thoracic cavity, the heart was found to be greatly enlarged. The lungs were very bloodless. I cut the art. aorta there where it appears as the descending aorta, but I could not find the great ascending vessels that have their origin in this interspace. At the descending aorta, I noticed some "ascending vessels."

LIFE HISTORY AND CASE HISTORY OF THE INFANT

Before birth, even in the last days, the infant only made very weak, hardly palpable movements. After birth, it showed a weak life, lying half-days nearly without any movement, without uttering a tone. When it was supposed to take the breast, it was sucking two to three times and then started crying and coughing, as if it was so lacking vigor and respiratory power that it could only be nourished with the greatest difficulty. When it was 3 weeks old, a rash developed over the entire body and the skin was peeled almost completely, so that it was almost impossible to touch it. From that time on, the skin, the mouth, and the nails turned blue, and they remained so until the infant's death. Rarely did the infant sleep for > 2 h continuously, suddenly starting to cry loudly, struggling with its hands, and moving its feet convulsively backward; then the mouth, the tongue, and the nails became almost dark blue, and the infant could be calmed only by being turned oil its left side and being rocked vehemently. Convulsions of this kind occurred repeatedly, in particular when bowel movements were not regular. However, these usually occurred four to five times a day. In this manner, the infant lived for almost 27 weeks, as (4 days before its death) it seemed to recover, getting more lively and smiling more often. Two days later, during the night it suddenly started to cry heavily, the above-mentioned attacks increased in frequency and severity, and at noon of the fourth day it finally passed away peacefully.

Now I report the results of my anatomic examination. On external examination, the heart itself was rather well formed, only the right atrial appendage (auricula dextra) was found to be of large size, the left (sinistra), however, was of small size. Both cavae, with the superior being cut just above the right atrium, and the pulmonary veins, of which one was torn apart, did not show any abnormalities. However, an aorta seemed to be missing altogether, whereas the pulmonary artery (art. pulmonalis), which was much larger than usual, continued as the arterial duct (ductus arterios. Botalli), after having given rise to the two branch pulmonary arteries. Unfortunately, the cut was made so close to the origin of the pulmonary branches that only by conclusions from other known facts some clarity can be gained about the relation of this big ductus (Duct. Art) to the descending aorta (Aorta descend.) and to the arteries originating from the aortic arch (Arcus aortae).

A more detailed preparation of the pulmonary artery (art. pulmonalis) revealed a canal lying next to, right of, and posterior to it, with the preparation of its course leading me to the coronary arteries, which also gave rise at their posterior circumference to a pair of very thin little branches. Between the two coronary arteries, this canal continues behind the pulmonary artery as a thin solid cord toward the left side of the heart. This cord is the diseased obliterated part of the aorta, the part of the canal by which the blood from the descending aorta had to flow backward to reach the coronary arteries. What usually is the ascending aorta (aort. ascendens) and aortic arch (arcus aortae) in this case was nothing but the origin of the two coronary arteries, by which they arose from the descending aorta (aort. desc.).

The interior of the heart revealed the following. Both cardiac cavities on the right side are considerably enlarged. In the right atrium the pectinate muscles (msuculi pectinati) are developed very strongly. The orifice of the coronary sinus is normal. The Eustachian valve (valvula Eustachii) is large, the tubercule of the lower (tuberculum loweri) is indistinct. The valve of the foramen ovale (valvula foraminis ovalis) is strongly deviated to the right and by far does not close the oval foramen completely. At the anterior superior circumference of it, there is a widely patent opening of the size of a crow-quill. The tricuspid valve (valvula tricuspidalis) is thick and muscular, similar to that found in a bird's heart. The semilunar valves of the right ostium arteriosum are of unusually large size, with very prominent nodules, and they close very perfectly. The left atrium measures at most the fourth part of the right atrium and the left auriculoventricular aperture (ostium venosum) of the left ventricle is very small, so that it can hardly be seen from the opened atrium. The left ventricle itself is reduced in size to a small inferiorly two-tipped cavity only 17 mm in height and with a transverse diameter of 9 mm, measured at its largest circumference. The diameters of the muscular walls of this rudimentary ventricle at its thinnest parts measure 10 mm, at its thicker parts 20 mm, whereas the same measures 9 mm maximally within the right cardiac chamber, and at its thinnest parts only 6 mm. The mitral valve (valvula mitralis) is, in proportion to the size of the ventricle, ordinarily developed. The interior wall of the chamber is entirely smooth and normal. There, where the ostium arteriosum is supposed to be, over a small distance a thin swine-bristle can be advanced into a blind-ending canal. Any communication between the ventricle and the aorta cannot be found.

The preceding anatomic description will be illustrated by the enclosed (Figs 1-4). For these, I am indebted to the skilful hands of Dr. W. Hillebrand, my former hearer, to whom I herewith publicly express my gratitude.

[FIGURES 1-4 OMITTED]

The mechanism of the circulation in this malformed heart must have been as follows. The venous blood of the venae cavae entering the right atrium was expelled to the right ventricle by its contraction. The entry into the left atrium through the widely patent foramen ovale was impossible; on the contrary, again and again the blood coming from the lungs entering the left atrium through the pulmonary veins had to make its way to the right atrium via the foramen ovale and had to, mixed with the venae caval blood, reach the right ventricle, after having been expelled to a very little extent into the blind-ending small left ventricle and having been regurgitated from it. By their function, the left atrium and the left heart chamber, therefore, had to be considered as diverticula of the right ventricle only. Functionally, in this heart there was but one chamber, the right. From this the mixed blood streamed into the former left aorta (Art. pulmonalis), from which two branches led a part of it to the lungs, while the largest amount continued its way through the further continuation of this left aorta (Ductus art. Botall.) to the descending aorta (Aorta descendens). Undoubtedly, at that spot where normally both aortae are confluent, the common trunk of the Arteriae coronariae cordis (the degraded aorta proper) originated, in which the blood streamed backward to the heart for its nutrition. From the above-mentioned account of the dissecting physician, it is probable that the trunks for the upper part of the body did not originate from the descending aorta (Aorta descendens). If the thoracic viscera had been removed properly (lege artis), it would have been easy to receive information on this interesting point.

It is very obvious to compare this heart to an amphibian heart if one considers the functional significance of its several parts, for it indeed consisted of a single atrial and a single ventricular chamber only; into the former venous and arterial blood were flowing together, and from the latter not only the whole body but also the lungs received their blood. The bloodstream to the lungs was a fraction of the bloodstream to the body, and only a small part of the blood mass was breathing. A comparison of this kind might suggest an original malformation to be the cause for this malformation. This must, however, be rejected by all means. We can well contend with certainty that the cause was an adhesive inflammation of the aortic orifice (ostium arteriosum) of the left ventricle, which developed at a time when all single parts of the heart already had been formed in a permanent manner but were of small size, perhaps during the third month. By such an assumption, all deviations from the natural condition can be explained easily and completely. Even the enormous hypertrophy of the walls of the left ventricle would have to be understood as a consequence of the almost obstructed stenosis of the aortic orifice (ostium arteriosum). Only the inferior origin of the branches for the upper body part (if it really took place) would always have to be explained as a variety that is independent from this. To say anything with certainty, however, about what caused the inflammation (local arteritis) that I assumed, probably belongs to the most difficult parts of the difficult etiology of the illnesses of the fetus. Finally, it is evident that an individual with such an amphibian heart could not live indefinitely; on the contrary, it is astonishing that it had lived for such a long time. In the interest of science, we must regret that no observations were made on the infant's temperature and that auscultation had not been performed; both would certainly have revealed interesting results. Among the symptoms listed in the above-mentioned case history, cyanosis doubtlessly is an indispensible consequence of the "amphibian heart." Did it not become apparent in the first 3 weeks of life, because at the beginning of extrauterine life the skin respiration through the thinner and more humid epidermis could take place more easily and was able to substitute for the insufficient oxygenation of the blood in the lungs? Or did the venous stasis only develop gradually? A clear answer should be impossible altogether given the hitherto investigations on cyanosis. The sluggishness and the weakness of the movements can be explained here, as in all similar cases, from the imperfect nutrition of the muscles and nerves by the almost completely venous blood. The occurrence of respiratory distress while sucking can be, apart from this, also substantiated by the fact that the qualitatively little efficacious function of the lungs could not be interrupted even for a short moment without instantaneously causing the danger of complete asphyxia.

REFERENCES

(1) Noonan AJ, Nadas AS. The hypoplastic left heart syndrome: an analysis of 101 cases. Pediatr Clin North Am 1958; 5:1029-1058

(2) Romberg ELR. On arctation and closure of the arteries in disease. Edinburgh Med Surg J 1846; 65:149

(3) Canton. Congenital obliteration of origin of the aorta. Transactions of the Pathological Society of London 1848-1849/ 1849-1850; 2:38

(4) Bardeleben K. Obliteration of the left ostium arteriosum in the heart of a half-year old infant. In: Virchow R, Reinhardt B, eds. Archiv fur pathologische anatomie und physiologie und fur klinische medicin (vol III). Berlin, Germany: G. Reimer, 1851; 305-312

* From the Children's Hospital, Department of Pediatric Cardiology, Westfaelische Wilhelms-Universitaet Muenster, Muenster, Germany.

Manuscript received December 1, 2000; revision accepted March 21, 2001.

Correspondence to: Josef Gehrmann, MD, Children's Hospital Department of Pediatric Cardiology, Westfaelische Wilhelms-Universitaet Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, Germany; e-mail: JGehrman@uni-muenster.de

COPYRIGHT 2001 American College of Chest Physicians
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