Case reports

Systolic prolapse of the mitral valve in

Noonan’s syndrome

William 1~. Towne, M.D.* (‘hicagu. II/. John S. Fabian, M.D.“‘* (‘le~~rlnnd. Ohm Kenneth M. Rosen, M.D.*** ( ‘hicngv:o, Iii. Shahbudin H. Rahimtoola, M.D., F.R.C.P.**** I+wtlntlcl. ow.

Turner’s syndrome has been frequently asso- ciated with cardiovascular malformations, most commonly coarctation of the aorta.’ Noonan’s syndrome shares many features with the Turner syndrome but differs in that chromosome studies reveal a normal genotype. The cardiac lesion most frequently encountered has been pulmonic stenosisz- The purpose of this communication is to report a patient who presented with the signs of Noonan’s syndrome and was found to have sys- tolic prolapse of the mitral valve with mitral regurgitation.

Case report A thirty-five-year-old Negro woman was admitted for eval-

uation of cardiovascular disease. She had been born prema- turely with a hirth weight estimated to be four pounds. Multiple skin and pulmonary infections were noted in child- hood. At the c,onclusion of her only pregnancy at age 25, she gave premature birth to a four-pound male infant. Cesarean

section was performed for obstetric indications and revealed grossly normal internal genitalia.

The patient denied all cardiac symptoms. There was no history of rheumatic fever. There was no family history of congenital malformation or mental retardation.

Physical examination revealed a poorly developed Negro woman appearing older than her stated age (height 59 inches, wkight 85 pounds). Slight frontal bossing, ocular hypertelor- ism (intercanthal diameter 4.5 cm.), bilateral ptosis, ptery- gium colli, micrognathia. and posteriorly rotated pinnar were apparent on inspection (Fig. 1). Also noted were a broad nose with wide ala nasi, a low-set posterior hairline, and a some- what low-pitched voice. The skin was soft and rather hyper- elastic. The lungs were clear and the liver and spleen were not palpable. Pelvic examination revealed no abnormalities. Neurologic examination was entirely negative except for mild mental retardation.

Examination of the cardiovascular system revealed the pulse to be 84 per minute and regular. The blood pressure was 110/W mm. Hg in both arms and 130/X0 in the lower extremi- ties. Jugular venous pulse was normal. A slightly hyperactive apex beat was palpable in the fifth left intercostal space at the anterior axillary line. On auscultation the first and second heart sounds were normal. A loud, snapping midsystolic click was heard at the apex and radiated widely. A grade III/VI, late systolic murmur was heard at the apex. It radiated well to the axilla and to the base. The click could be moved earlier in systole by standing the patient upright or 1~ inhalation of amyl nitrite.‘?

Hoentgenographic skeletal survey revealed Prrthr’s disease of the left hip. Riomicroscopy and skin biopsy were normal. A buccal smear showed 26 per cent sex chromatin p&rive. Chromosome analysis of 50 hlood lympho<,ytrs showed a 46XX pattern.

Special studies. A phonocardiogram confirmed the auscul- tatory findings described above. Four roentgenographic views of the heart with barium swallow revealed moderate c,ardio- megaly with enlargement of the left ventricle. Left atria1 enlargement could not be detected. An electrocardiogram (Fig. 2) revealed right-axis deviation (mean ()RS axis in the

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Towne et al.

Fig. 2. Electrocardiogram showing right-axis deviation.

Fig. 1. Photograph of patient demonstrating ptosis, hyper- telorism, and broad ala nasae.

frontal plane of plus 120°) and clock-wise rotation in the horizontal plane. Cardiac catheterization revealed a normal resting cardiac index with normal intracardiac and intravas- cular pressures. Selective tine (SO’ left anterior oblique projec- tion) and cut-film biplane retrograde left ventriculography de- monstrated systolic prolapse of the mitral valve (Fig. 3) with mild to moderate mitral regurgitation. In the anteroposterior projection (Fig. 4) a localized bulge in the superolateral aspect of the left ventricular wall was seen to project into the cavity of the left ventricle both in systole and in diastole. Retrograde ascending aortography revealed a competent aortic valve and a normal thoracic aorta. On a subsequent occasion, a selective cineangiogram of the right ventricle in the anteroposterior projection showed the outflow tract and pulmonary valve were normal.

Comments

In 1963, Noonan and Ehmke” reported the com- bination of Turner phenotype, normal genotype, and congenital heart disease in nine children. In 1965, Summitt and Opitz* proposed that the term Noonan’s syndrome be used to designate such patients and that as a group they were separate and distinct from subjects with the Turner syndrome.

The more common features of Noonan’s syn-

drome include short stature, hypertelorism, ptosis, micrognathia, pterygium colli, chest de- formities, congential heart disease, and mental retardation. Pulmonic stenosis has been the car- diovascular anomaly found in the majority of cases including those originally reported by Noonan.‘-“, *-I” However, atrial-septal defect,’ patent ductus arteriosus,” and Ebstein’s anoma- ly,‘” as well as coarctation of the aorta and aortic stenosis” have also been reported with Noonan’s syndrome.

Until 1961, midsystolic clicks and late systolic murmurs were felt to be extracardiac in origin.” In the past decade, intracardiac phonocardiog- raphy has shown convincingly that these auscul- tatory phenomena arise from the mitral valve ap- paratus.‘“-‘” Angiocardiography has, in every reported case, revealed systolic prolapse of one or both mitral valve leaflets into the left atrium usually with mild to moderate mitral regurgita- tion 6. 7. 12. 13. 16. 17

In most instances, patients with mitral valve prolapse have no symptoms of cardiac disability and are without other physical abnormalities.‘“, *‘J This condition has, however, been encountered in patients with Marfan’s syndrome.‘” The patho-

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Prolapse of mitral ualve in Noomrrr ‘s syndrome

Fig. 3. Lateral view of systolic frame from selective retrograde left ventriculogram revealing systolic prolapse of a portion of the mitral valve. Dye is seen entering the superior portion of the left atrium.

logic findings of mitral valve disease in Marfan’s syndrome as well as in the few patients with iso- lated mitral valve prolapse that have been described include enlargement of the mitral an- nulus, o&sized leaflets, and thinning and elonga- tion of the chordae tendineae. Myxomatous degeneration of the valve substance has been seen on microscopic examination.“,, Ii

The angiographic appearance of the bulge in the left ventricular wall of our patient is similar to that described by Ehlers and co-workers” in 10 patients with the Turner phenotype who had normal chromosome analyses and represents ec- centric hypertrophy of the left ventricle. The angiograms in their patients also revealed a bulge in the postero-inferior surface of the left ventricle which was not seen in our patient. With one ex- ception, their patients with this left ventricular anomaly had marked superior shift of the QRS axis in the frontal plane (-60’ to +- 180’). This

Fig. 4. Anteroposterior view showing opacrlic ation of left atrium, dilation of the mitral valve annulus. and a ioc,alizrd bulge in the superolateral aspect of the Left T ~~ntric~ular wall.

finding was also not present in our patient. None of their subjects were said to have any features of the midsystolic click-late systolic murmur syn- drome.

We have been able to find four c.aseP’: in the literature where either clinical or pathologic evi- dence of mitral valve prolapse was described in association with the classic Turner syndrome (proved X0 genotype and/or gonadal agenesis). The present patient appears to be the first re- ported instance where mitral valve prolapse has been found in association with Noonan’s syn- drome.

Summary

A thirty-five-year-old woman with Noonan’s syndrome (Turner phenotype with normal chro- mosome pattern) had mitral valve prolapse and mitral insufficiency associated with the ausculta- tory findings of a midsystolic click and late systolic murmur. Selective left-ventricular angio- cardiography also showed eccentric hypertrophy of the left ventricle. To our knowledge, this is the

American Heart Journal 501

Towne et al.

first reported instance of mitral valve prolapse occurring in association with Noonan’s syn- drome.

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