Embolic stroke, left atrial myxoma and gigantism in a patient with Carney complex with additional features suggestive of Marfan syndrome

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Case report

Embolic stroke, left atrial myxoma and gigantism in a patient with Carney complex with additional features suggestive of Marfan syndrome

Carlo Micelli,

¹

Wienta Diarsvitri,

¹

Dian Maria pia,

²

Hindarto Luhur

³

To cite: Micelli C, Diarsvitri W, pia DM, et al.

BMJ Case Rep published online First: [please include Day Month Year].

doi:10.1136/bcr-2018- 225093

1Department of Community Health, Faculty of Medicine, Hang tuah University, surabaya, east Java, Indonesia

2Department of Neurology, Dr. ramelan Naval Hospital, surabaya, east Java, Indonesia

3Department of radiology, Gotong royong Hospital, surabaya, east Java, Indonesia Correspondence to Dr Wienta Diarsvitri, diarsvitriw@ gmail. com accepted 9 July 2018

Summary

a 16-year-old boy presented to the emergency

department with a sudden weakness on the right side of the body and was diagnosed as having embolic stroke.

Later on, the patient was diagnosed as having Carney complex (CNC). the neurological complication might be caused by left atrial myxoma as a feature of CNC.

surprisingly, the patient showed some additional features such as positive wrist and thumb signs, pectus carinatum deformity and plain flat feet, suggestive of Marfan syndrome. this case demonstrated that both of these syndromes might coexist in the same patient, suggesting that proper diagnostic and management were key factors that affected prognosis. He showed an improved condition after he had received medical treatments, undergone tumour excision and physiotherapy. Further evaluation was needed to improve patient outcomes.

BaCkground

Carney complex (CNC) is an autosomal-dominant syndrome characterised by pigmented lesions of the skin and mucosa, cardiac, cutaneous and other myxomas and multiple endocrine tumours. CNC is a rare disease with an unknown prevalence.¹ The most common non-cutaneous lesions found in CNC are cardiac myxomas.² However, they may release detached tumour fragments or thrombi into the systemic circulation, leading to embolisation.

The cardiac disorders associated with CNC appear to be the most common causes for neurovascular complications in the patient.^{3 4}

The CNC features sometimes resemble to Marfan syndrome, because of embryological and genetic overlap between the cardiac and cutaneous systems. Marfan syndrome is an autosomal-dominant multisystem connective tissue disorder. It is interesting that both of these syndromes might coexist in the same patient because it is a rare condition that patient diagnosed as having a syndrome in combination with another different syndrome.

We reported a case of embolic stroke, left atrial myxoma and gigantism presenting in a patient with CNC with additional features suggestive of Marfan syndrome.

CaSe preSenTaTion

On 25 June 2016, a 16-year-old single boy of Java origin presented to the emergency department with a sudden weakness of his right arm and leg after

taking a predawn meal early in the morning. He also had difficulty talking and walking. He denied any headache, nausea, vomiting, fever, photo- phobia, double vision or recent trauma. No seizure had been witnessed. He never felt like this before.

He was an ex-smoker, but did not have any vascular risk factors such as hypertension, diabetes or dyslip- idaemia. He denied taking any drugs including cocaine, amphetamines and alcohol. There was no family history of similar complaints. The patient’s height, weight and body mass index were 185 cm, 70 kg and 20.45 kg/m², respectively. His blood pres- sure was 110/75 mm Hg. Other vital signs were within normal limit. Lungs were clear to ausculta- tion. Heart sounds were regular with no murmur.

There was no palpable lymphadenopathy, hepato- megaly or splenomegaly. Physical examination was limited by the patient’s reduced conscious state (GCS score 3-2-5), but the patient demonstrated motor lateralisation to the right side of the body.

Both pupils were isocoric. Neurological examination revealed paralysis of the right central facial nerve. He had neither evidence of nuchal rigidity nor tongue deviation.

Laboratory investigations including complete blood counts, blood glucose, liver functions, renal functions and electrolytes were within normal limits. On 25 June 2016, his chest X-ray showed normal appearance of the lung and no signs of pulmonary embolism or cardiomegaly. Three days later, a non-contrast-enhanced MRI showed large lesions on the left hemisphere, which showed a hyperintense appearance on T2-FLAIR image, but hypointense on T1-weighted image, and restricted lesion area on DWI with central area representing haemorrhage. Radiological findings were suggestive of an acute cerebral infarction with haemor- rhagic transformation on the left hemisphere from internal capsule and basal ganglia to corona radiata.

Magnetic resonance angiogram (MRA) showed left internal carotid artery occlusion with no aneurysm or arteriovenous malformation. The patient was diagnosed as having embolic stroke (figure 1).

TreaTmenT

The medicines used for his early treatment of embolic stroke were intravenous injection of 500 mg citicoline, 3 g piracetam and 250 mg tranexamic acid three times a day and vitamin K two times a day. On 6 July 2016, oral vitamin B complex and

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folic acid once a day were added to the medications to prevent endothelial dysfunction and accelerated atherosclerosis.⁵ He was discharged from the hospital on 9 July 2016. He was subse- quently referred for rehabilitation due to residual right-sided weakness and unsteadiness. The patient was also instructed to have a follow-up visit at neurology outpatient clinic in 2 weeks and continued once a month. His maintenance therapy consisted of citicoline 250 mg, piracetam 1200 mg two times a day; aspirin 80 mg, warfarin 2 mg, pentoxifylline 400 mg, methylcobalamin and folic acid once a day. His international normalised ratio (INR) was monitored every month to prevent recurrent stroke.⁶ The patient showed an improvement from his right-sided weakness each time he had a follow-up visit.

After a few consultations, the doctor realised the patient looked slender, thin and much taller than his parents. He also had spotty skin pigmentation on his face. On further examination, he had pectus carinatum deformity, plain flat feet and long

fingers. His thumb and wrist signs (Steinberg sign and Walk- er-Murdoch sign) were positive. Because the patient seemed to have had an abnormal linear growth of the body, he was referred to an internist. On 3 January 2017, his growth hormone (GH) result showed an increase to 20.6 ng/mL. He was diagnosed as having gigantism. On 5 January 2017, a second brain MRI was performed to evaluate the pituitary gland. The T2 coronal image revealed there was erosion on the floor of the pituitary fossa on the right aspect of the pituitary gland, suspicious for a pituitary microadenoma (figure 2). He received a half dosage of 2.5 mg bromocriptine, a dopamine-agonist for medical therapy of pituitary tumour,⁷ three times a day for 2 weeks, full dosage two times a day for 2 weeks and three times a day for maintenance.

On 18 January 2017, the patient came to the cardiology outpatient clinic due to chest tightness when he was tired.

Transthoracic echocardiogram (TTE) was performed to evaluate the aortic root. He was given oral spironolactone 25 mg Figure 1 Embolic stroke as depicted in MRI and MRA. Left: Diffusion weighted imaging (DWI) image. Middle: FLAIR image. Right: MRA AP view;

yellow arrow showed left ICA occlusion. ICA, internal carotid artery; MRA, magnetic resonance angiogram.

Figure 2 Erosion on the floor of the pituitary fossa on the right aspect of the pituitary gland. Left: T2-weighted sagittal image. Right: T2-weighted coronal image.

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and phenoxymethylpenicillin 500 mg once a day. On 14 March 2017, the TTE showed a mobile mass in his left atrium. A mass of 3.30 cm × 2.68 cm was discovered attached to the interatrial septum (IAS). The preoperative diagnosis was aortal myxoma.

He was scheduled for the tumour excision on 30 March 2017.

On 21 March 2017, the patient was admitted to the hospital

because of dyspnoea on exertion. He felt an unusual breath- lessness with chest discomfort during an activity. Warfarin and pentoxifylline medications were stopped. On 23 March 2017, TTE was performed to monitor the aortic root again. The first measurement of aortic valve was 23.7 mm. There was a white dotted line on the image added to improve the accuracy of measuring aortic valve. The additional line showed 98.0 pix, which equals to 25.9 mm. Sometimes the result might be slightly different because of the movement of the heart wall and blood flowing through the heart and large vessels (figure 3).

On 30 March 2017, the left atrial myxoma was successfully taken, along with the IAS. The defect made in the septum was closed using an appropriately sized patch harvested from the pericardium. After the excision, the patient was given intravenous injection of 1 g cefazolin and 1 g paracetamol (drip) three times a day; 50 mg ranitidine and 20 mg furosemide two times a day. On 3 April 2017, cefazolin was changed to intravenous injection of 200 mg cefixime two times a day. On 7 April 2017, the patient was discharged from the hospital.

ouTCome and Follow-up

The patient received maintenance therapy and his INR was monitored every month to prevent recurrent stroke. He had no complaint about his condition after he had undergone left atrial myxoma excision along with the IAS. A regular physiotherapy succeeded in increasing his condition from right-sided weakness. Moreover, his GH decreased to normal values by taking bromocriptine. He had a regular check-up schedule at outpatient clinics.

diSCuSSion

The patient was diagnosed as having CNC. To make the diagnosis of CNC, a patient must either exhibit two of the major criteria confirmed by histology, imaging or biochemical testing or meet one major and one additional criteria.¹ In this case, the patient had cardiac myxoma, gigantism and spotty skin pigmentation on his face, that were included in the major criteria of CNC. The aetiology of the gigantism was more likely due to pituitary microadenoma, which was less than 10 mm in size. In order to ensure the diagnosis of pituitary microadenoma in this patient, postcontrast and especially thin-section dynamic contrast-enhanced imaging in the coronal and sagittal planes needed to be performed. Contrast-enhanced MRIs have a sensitivity of 90% and significantly improved diagnostic accuracy.⁸

The patient came to the hospital with embolic stroke, which might be the complication of embolisation from detached cardiac tumour fragments.^{9 10} Embolic stroke may occur any time with progression of the tumour. This is why early detection and regular screening with echocardiography are essential.¹¹ Immediate management of stroke could save lives and reduce the long-term effects of stroke.¹² The effects of a stroke depend on several factors, including the location of the obstruction and how much brain tissue is affected.

However, because one side of the brain controls the opposite side of the body, a stroke affecting one side will result in neurological complications on the other side of the body. If the stroke occurs in the left side of the brain, the right side of the body will be affected, producing some or all of the following: paralysis on the right side of the body, speech/

language problems, cautious behavioural style or memory loss.

Figure 3 Aortic root and mass as depicted in TTE. Top: TTE on 14 March 2017 showed a mass. Middle and Bottom: TTE on 18 January 2017 and 23 March 2017 showed aortic root progression. TTE, transthoracic echocardiogram.

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In contrast, some additional features of the patient were suggestive of Marfan syndrome, which is currently diagnosed using the Ghent criteria. In the absence of family history, a patient is diagnosed as having Marfan syndrome if aortic root diameter (Z-score ≥2) and systemic scores≥7 points.¹³ The Z-score of this patient was calculated by using aortic root Z-score calculator from Halifax.¹⁴ All of the patient’s latest Z-score was ≥2, except sinus of valsava (Z-score=1.92). But according to Wessex, the patient’s Z-score of sinus of valsava was 2.06.¹⁵ The scores were increased in 2 months from January to March (table 1). The patient exhibited pectus carinatum deformity (two points), plain flat feet (one point) and also his wrist and thumb signs were positive (three points).

The total systemic scores of the patient were six.

Despite physical and radiological findings, genetic testing was not possible to perform due to limited setting. Although it is known that mutations in the FBN1 gene is the predominant cause of classic Marfan syndrome, there is no rapid and efficient molecular diagnostic test that showed high sensitivity and spec- ificity.^{16 17}

This case showed that imaging modalities such as MRI, MRA and echocardiography are essential to diagnose cases like this.

A patient with both CNC and Marfan syndrome is a very rare case with multiorgan involvement that requires optimal multidisciplinary care to improve both patient’s prognosis and quality of life.

learning points

► A patient having both Carney complex (CNC) and Marfan syndromes is a very rare case with multiorgan involvement that should be considered if the established criteria are met.

► Imaging modalities such as MRI, magnetic resonance angiogram and echocardiography are essential in early detection, screening and diagnosis of CNC and Marfan syndrome.

► If a genetic testing was not possible to perform, established diagnostic criteria can be used to rule out other possibilities.

► It requires an optimal multidisciplinary care to improve both patient’s prognosis and quality of life.

Contributors Conception and design of study: CM, WD. acquisition of data: CM, DMp. analysis and interpretation of data: CM, DMp, HL. Drafting the article: CM, WD.

Critical revision of the article: CM, WD. Final approval of the version to be published:

CM, WD, DMp, HL.

Funding this research was funded by the Faculty of Medicine, Hang tuah University, surabaya, east Java, Indonesia

disclaimer all persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing or revision of the manuscript. Furthermore, each author certifies that this material or similar material has not been and will not be submitted to or published in any other publication before its appearance in the BMJ Case report.

Competing interests None declared.

patient consent obtained.

provenance and peer review Not commissioned; externally peer reviewed.

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Table 1 Aortic root data on 18 January 2017 Site

18 January 2017 23 march 2017

measured (mm) Z-score measured (mm) Z-score

Aortic valve 25.4 2.25 25.9 2.43

Sinus of valsava 32.2 1.68 33.0 1.92

Sinotubular junction

25.5 1.33 28.8 2.44

Ascending aorta 26.0 1.03 29.1 2.27

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