Paraganglioma syndrome type 4 presenting as hypertensive encephalopathy in an 8-year-old boy


Hippokratia 2020, 24(3): 143

Kousta E1, Sdogou T2, Papathanasiou A1
1Department of Pediatric Endocrinology, 2Second Department of Pediatrics, University of Athens, “P & A Kyriakou” Children’s Hospital, Athens, Greece

Keywords: Paraganglioma, succinate dehydrogenase B mutation, child, catecholamines

Corresponding author: Dr Asteroula Papathanasiou, MD, PhD, 8 M.Botsari str., 15239 Nea Pendeli, Athens, Greece, tel: +306945463393, e-mail:

Dear Editor,

Paragangliomas (PGL) are rare catecholamine-secreting tumors deriving from the paravertebral ganglia1,2. Τhey are often associated with genetic mutations in the succinate dehydrogenase (SDH) complex (SDHB> SDHD> SDHC genes)3. There are only a few SDHB mutation-related cases described in children. We report the case of an 8-year-old boy with PGL type 4 syndrome presenting as an emergency with status epilepticus due to hypertensive encephalopathy, which is an unusual presentation of catecholamine excess. The disease progress was typical with recurring tumors and metastases. This case contributes to physicians’ awareness of the non-specific symptoms of catecholamine secreting tumors and points out the severity of the disease in patients with SDHB mutations and the importance of genetic screening.

The boy presented with generalized seizures and hypertension and, on admission, went over to status epilepticus. His symptoms had started ten months before; he developed mild headaches, dizziness, and lately nocturnal enuresis. Symptoms of a catecholamine-producing tumor in children can occasionally be non-specific (such as blurred vision, polyuria, polydipsia, and behavioral problems).  No information regarding family history was available, as the patient was adopted.

Laboratory investigations showed massively elevated 24-hour urine normetanephrine and dopamine. A magnetic resonance imaging of the abdomen revealed a 4.0 x 4.5 x 3.0 cm extra-adrenal paraganglioma, which was laparoscopically excised. Eighteen months later, symptoms recurred, and three new paragangliomas were excised laparοscopically. DNA analysis showed that the patient was heterozygote of the P254fsX255 germline mutation of the SDHB, a previously described mutation1,3. Because of the high incidence of hereditary PGL, genetic counseling and screening for mutations are mandatory to improve the follow-up of the patients and detect asymptomatic mutation carriers among relatives.

Three years after the second operation, a tumor on the left adrenal was excised by open abdominal surgery, showing malignant transformation and metastatic lesions in two thoracic vertebrae. It is typical for SDHB-related PGL to recur often2,3 and have a high malignant potential (35-70 %)1-3. Size of the primary tumor more than 4.5 cm is related to earlier development of metastases, whereas patients diagnosed at a younger age seem to have improved survival3. The patient showed a mild disease progression over the next nine years following the diagnosis of metastatic paraganglioma.

In conclusion, this is a case report of a boy with PGL type 4 carrying an SDHB gene mutation. The patient presented with signs of hypertensive encephalopathy, which is unusual and should be included in the differential diagnosis of children presenting with seizures. Early diagnosis in children is important, as catecholamine hypersecretion in these tumors is related to high cardiovascular morbidity and mortality. Furthermore, patients have an increased risk for recurrence and malignant transformation and require lifelong monitoring. Genetic counseling and testing of family members to detect early asymptomatic disease carriers among relatives are mandatory.

Conflict of interest

Authors declared no conflict of interest.


1. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. Pheochromocytoma and Paragan-glioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99: 1915-1942.
2. de Tersant M, Généré L, Freyçon C, Villebasse S, Abbas R, Barlier A, et al. Pheochromocytoma and Paraganglioma in Chil-dren and Adolescents: Experience of the French Society of Pediatric Oncology (SFCE). J Endocr Soc. 2020; 4: bvaa039.
3. Jochmanova I, Abcede AMT, Guerrero RJS, Malong CLP, Wesley R, Huynh T, et al. Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. J Cancer Res Clin Oncol. 2020; 146: 1051-1063.