Postgrad Med J (1992) 68, 37 - 40 D The Fellowship of Postgraduate Medicine, 1992

Cerebral arteriovenous malformation in Noonan'ssyndrome

F. Schon, J. Bowler and M. Baraitserl

Department ofNeurology, Atkinson Morley's Hospital, Copse Hill, London, SW20 ONE and 'Institute ofNeurology, National Hospitalfor Nervous Diseases, Queen Square, London, WCIN 3BG, UK

Summary: Noonan's syndrome involves the association ofmultiple congenital abnormalities includingneck webbing, pectus excavatum, facial anomalies with a variety of cardiac defects. In this paper theassociation of Noonan's syndrome with a large cerebral arteriovenous malformation is reported.Congenital cerebrovascular abnormalities are not a recognized feature of the syndrome. The paper alsoreviews previous reports of neurological associations with Noonan's syndrome, the commonest being mildintellectual impairment and ptosis.

Introduction

Noonan and Ehmke' first described a syndrome ofmultiple congenital abnormalities in 1963 which isnow thought to be a genetically determined condi-tion with autosomal dominant inheritance. Thecardinal features of the syndrome involve shortstature, congenital heart disease, webbed neck,pectus excavatum and facial anomalies.2 Mostreview articles are agreed that the syndromeinvolves in addition to abnormalities of growth,cranio-facial development and cardiovascular de-fects, changes in the genitourinary, skeletal,ectoderm and lymphatic systems.3 However, thequestion of whether neurological changes occurany more often than chance is unresolved. Num-erous individual case reports exist linking Noo-nan's syndrome (NS) with a variety of neurologicaldisorders. In this paper a case ofNS associated witha cerebral arteriovenous malformation is describedand the neurological associations of NS arereviewed.

Case report

A 35 year old Caucasian male electrician presentedwith a 5 year history of increasing right sidedptosis, mild ptosis on the left and minor left armweakness. His past history included bilateral con-genital inguinal herniorrhaphy and surgery for lefttalipes equinovarus. His parents (who were non-consanguinous) and his 5 siblings were unaffected.On examination he was of short stature (5 ft 1 in)

with short curly black (woolly) hair. He had noeyebrows, his ears were posteriorly rotated, hisneck webbed, his skin unusually lax and his chestshowed pectus carinatum superiorly and pectusexcavatum inferiorly (Figure 1). There was a mildscoliosis. The main neurological findings werebilateral ptosis most prominent on the right, extra-ocular movements in the right eye were limitedwith elevation, abduction and adduction beingmarkedly impaired. There was a mild left spastichemiparesis with brisk left-sided reflexes andbilateral extensor plantar responses. Higher mentalfunction was normal. There was a loud cranialbruit and arterialized conjunctival vessels. Cardiacexamination revealed a prominent right ventricularimpulse and a pulmonary systolic murmur.A computerized tomographic (CT) brain scan

with contrast enhancement revealed an extensivebasal arteriovenous malformation, with largedraining veins in the region of the right cavernoussinus. Deep within the right hemisphere was apresumed porencephalic cyst (Figure 2). Cerebralangiography was not carried out. His partial thirdnerve palsy may well have been due to pressurefrom the enlarged veins in the region of thecavernous sinus.Echocardiography showed right ventricular

hypertrophy and mild tricuspid regurgitation.Doppler studies suggested slightly raised pul-monary arterial systolic pressure but arterialoxygen saturation was 97% implying any pul-monary arteriovenous shunt must be small.The patient had no cardiovascular symptoms or

signs and his chest X-ray, electrocardiograms andechocardiogram were unremarkable.

Correspondence: F. Schon, Ph.D., M.R.C.P.Accepted: 8 May 1991

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Figure 1 Patient showing tightly curled hair, absent eyebrow hair, prominent ptosis most marked on the right,webbing of the neck. (Reproduced with the consent of the patient.)

Discussion

The cardiovascular abnormalities associated withNS are interesting in that they not only involve theheart itself (such as pulmonary stenosis, atrialseptal defects, hypertrophic cardiomyopathy andventricular septal defects) but also a wide variety ofabnormalities ofthe major arteries and veins withinthe chest such as coarctation, patent ductus art-erosis, anomalous venous drainage, and brachio-cephalic vessel abnormalities.4'5 Changes in theveins and lymphatics extending beyond the thoraxhave also been described.4'5 It is therefore opento speculation whether cerebrovascular changesmight be expected in NS. The present case involvesa very extensive cerebral arteriovenous malforma-tion. As with all isolated case reports the questionarises of whether the association is purely due tochance. There are no similar cases in the literature.However, McAnena et al.6 described a case ofsubarachnoid haemorrhage arising from a leftposterior communicating artery aneurysm in asso-ciation with NS. There are no systematic studies ofthe cerebral vasculature in NS which would be hardto carry out during life.A variety of other neurological conditions have

been described in association with NS. The com-monest is developmental delay and mild mentalretardation.7'8 Ptosis is also recorded in many

studies9 without evidence of a generalized myo-pathy, although an association between NS andmalignant hyperpyrexia has been suggested.'0 Twocases of NS in association with cerebellar ectopiahave been reported.""2 It is not clear whether this isrelated to their short and webbed neck. A possibleoverlap between NS and neurofibromatosis hasalso been suggested in some families.'3"'4 There arenumerous reports of NS being associated with awide variety of isolated neurological conditions,these include a temporal lobe anomaly,'5 hydro-cephalus,2 cerebral abscess'6 and malignant Sch-wannoma. 17

In 1988 Reynolds et al.'8 described 8 patientswith multiple congenital anomalies and mentalretardation which they called the cardio-facial-cutaneous or CFC syndrome. These authorspointed out that there are some shared featureswith Noonan's syndrome. However, severe mentalretardation and abnormal neurological findingsare clearly much commoner in the CFC syndromethan in Noonan's syndrome.

In view ofthe wide range ofmanifestations ofNSinvolving many systems it would perhaps be sur-prising if the nervous system was spared. Largestudies are needed to define any involvementpossibly involving computerized tomographic ormagnetic resonance imaging brain screening.

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Figure 2 Computerized tomographic brain scan showing an extensive basal arteriovenous malformation with largedraining veins (arrowheads) in the region of the right cavernous sinus and a cyst deep within the right hemisphere.

References

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2. Noonan, J.A. Hypertelorism with Turner phenotype. A newsyndrome with associated congenital heart disease. Am J DisChild 1968, 116: 373-380.

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4. Pearl, W. Cardiovascular anomalies in Noonan's syndrome.Chest 1977, 71: 677-697.

5. Lam, J., Corno, A., Oorthuys, H.W.E. & Marcellettic, E.Unusual combination of congenital heart lesions in a childwith Noonan's syndrome. Ped Cardiol 1982, 3: 23-26.

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6. McAnena, O., Buckley, T. F. & Padilla, J.R. Intracranialaneurysm in association with Noonan's syndrome. Irish MedJ 1984, 71: 140-141.

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9. Schwartz, D.E. Noonan's syndrome associated with ocularabnormalities. Am J Ophthalmol 1970, 73: 955.

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11. Ball, M.J. & Peiris, A. Chiari (type 1) malformation andsyringomyelia in a patient with Noonan's syndrome. J NeurolNeurosurg Psychiat 1982, 45: 753-754.

12. Kobayashil, I., Aikawa, T., Titakemiya, T., Maruyama, S. &Takaho, K. Noonan's syndrome with syringomyelia. Jap JPsych Neurol 1986, 40: 101-104.

13. Meineoke, P. Evidence that the neurofibromatosis-Noonansyndrome is a variant of Von Recklinghausenneurofibromatosis. Am J Med Genet 1987, 26: 741-745.

14. Allanson, J.E., Hall, J.G. & Van Allen, M.I. Noonanphenotype associated with neurofibromatosis. Am J MedGenet 1985, 21: 457-462.

15. Gorke, W. Zerebrale anomalien bei Noonan syndrome.Clinik Pediatr 1980, 192: 577-581.

16. Unnithan, R.R., Bahnleyant, C.G. & Matnewroy, V.C.Noonan syndrome. Assoc Physic India 1985, 33: 177-179.

17. Kaplan, M.S., Optiz, J.M. & Gosset, F.R. Noonan's syn-drome. A case with elevated serum alkaline phosphataselevels and malignant schwannoma of the left forearm. Am JDis Child 1968, 116: 359-366.

18. Reynolds, J.F., Neri, G., Jermann, J.P. et al. New multiplecongenital anomalies/mental retardation syndrome withcardio-facio-cutaneous involvement-The CFC syndrome.Am J Med Genet 1986, 25: 413-427.

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