medwireNews: Researchers advise annual screening for tumours in children with mutations in the SDHB gene, starting from the age of 5 years.
These mutations are associated with around a quarter of all phaeochromocytomas and paragangliomas detected in children and nearly three-quarters of metastatic cases, highlighting the value of screening in mutation carriers, say Helen Storr (Barts and the London School of Medicine and Dentistry, UK) and study co-authors.
The team’s recommendations are based on an analysis of 38 patients seen in a joint dedicated paediatric and adult family outpatient clinic and treated at their centre, plus the results of a literature search.
From the latter, they found that although patients develop tumours at an average age of 29 years, the youngest reported patient with a tumour was 6 years old and the youngest with metastatic disease was aged 9 years, hence they advise beginning screening at age 5 years.
However, they stress that this cutoff is “arbitrary” and should “be regularly reviewed as more data become available”.
The 38 children treated at their centre included eight index cases with phaeochromocytomas or paragangliomas, diagnosed at a median age of 15 years, and 30 mutation carriers without symptoms, who underwent genetic testing at a median age of 6.8 years.
All the index cases underwent successful surgical resection, although three developed further tumours in adulthood, with two dying from metastatic disease. Twenty-seven of the asymptomatic carriers remained free of tumours during a median 5 years of follow-up, but five tumours were detected in three patients at intervals ranging (for first tumours) from the very first screening exam to 6 years after joining the screening programme.
“The risk of a child with an SDHB mutation developing disease during childhood is very low, but if tumours arise they are potentially more aggressive than adult-onset lesions, although the reason for this is unknown”, comment the researchers in Endocrine Connections.
They add that “early disease detection and intervention has the potential to cure a condition for which there are currently no satisfactory medical options once metastatic disease is established.”
For the surveillance protocol, Storr and colleagues suggest annual 24-hour urine metanephrines, or plasma metanephrines for older children (>10 years), along with abdominal scanning, because “the vast majority” of tumours in children with SDHB mutations are abdominal.
They note that magnetic resonance imaging (MRI) is the preferred imaging method, for its high accuracy and avoidance of radiation exposure in young children. However, they concede that young children may not tolerate long periods in a scanner and suggest abdominal ultrasound as an alternative in those aged 10 years or younger with normal metanephrines, although they stress that MRI should be introduced as soon as tolerated.
From the age of 10 years, the team recommends alternating abdominal MRI with MRI of the neck, thorax, abdomen, and pelvis.
“The rationale for this is that the earliest reported SDH-related disease at body sites other than the abdomen is aged 9 years”, they explain.
By Eleanor McDermid
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
Endocr Connect 2019; doi:10.1530/EC-18-0522