Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.

BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.

Fumarase deficiency in dichorionic diamniotic twins.

Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.

Language skills in a child with Leber hereditary optic neuropathy following intrathecal chemotherapy for acute lymphoblastic leukemia.

The language skills of a male child with Leber hereditary optic neuropathy (LHON) and coincidentally treated for acute lymphoblastic leukemia (ALL) with intrathecal chemotherapy at the age of 3 years 8 months were comprehensively evaluated twice over a 6-month period approximately 5½ years after diagnosis of ALL. Despite marked chemotherapy-related leukoencephalopathic changes documented on magnetic resonance imaging, the child presented with stable language skills, which were generally average to above-average based on the normative data from a comprehensive language test battery. In light of the coincidental presentation in the child of a diagnosis of LHON, which may lead to serious vision impairment and increased vulnerability to drug neurotoxicity, coupled with a history of central nervous system (CNS)-directed treatment for ALL resulting in progressive white matter pathology, the study highlights the importance of ongoing monitoring of the child's language development throughout his adolescent years.