O02 A case for diagnosis: ectodermal dysplasia and severe myelodysplasia

Abstract

Abstract A 13-year-old girl was referred to us by our paediatric colleagues due to vulval dermatitis. She had a history of congenital hypotrichosis, microcephaly, abnormal dentition, dyshidrosis manifest as recurrent febrile seizures in infancy, recurrent infections, neutropaenia and macrocytosis. Her father and younger brother have a similarly striking phenotype, with complete absence of scalp and body hair, abnormal teeth, abnormal sweating, but normal nails. In addition, the father has required a stem cell transplant for myelodysplastic syndrome. None of the family have keratoderma, cleft palate, ectrodactyly or cardiomyopathy. DNA from our index patient was sent to Cardiff for the ectodermal dysplasia (ED) plus 70 gene panel for next-generation sequencing, but no mutation was found. Our paediatric haematology colleagues sequentially arranged dyskeratosis congenita panel, myeloid panel, and whole-exome sequencing for the younger brother, which did not identify a causative mutation. Unusually, all three were found to have mosaic trisomy 18. The transmission of trisomy 18 from parent to child as a mosaic trait in both generations is extremely unusual, and mosaic trisomy 18 has not been previously reported to cause ED. We would appreciate any input on a genetic diagnosis for this family with a distinctive phenotype consistent with hypohidrotic ED associated with myelodysplasia, with extensive genetic testing revealing a potentially spurious or coincidental mosaic trisomy 18 in all three affected family members.