Neurofibromatosis 1 in the setting of dual diagnosis: Diagnostic and management conundrums

Karthik Muthusamy, Aseel El-Jabali, Laura J. Ongie, Radhika Dhamija, Dusica Babovic-Vuksanovic

Research output: Contribution to journalArticlepeer-review


Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder characterized by development of pigmentary skin changes, neurogenic tumors, and other manifestations involving multiple organ systems. Penetrance is complete, though expressivity is quite variable even among the family members. Given that NF1 is a common hereditary condition, existence of a second genetic disorder in NF1 patients is not unexpected. During comprehensive evaluations of individuals with NF1, we encountered 11 patients with dual diagnosis who contributed to phenotypic complexity and challenges for long-term management. Examples include Prader–Willi Syndrome, Autosomal Dominant Polycystic Kidney Disease, Down syndrome, infantile myofibromatosis, Craniosynostosis, cleft lip and palate, 47,XYY, 22q11.2 duplication, 15q13.3 deletion syndrome, and BRCA2- and ATM- related cancer predisposition syndromes. Presence of dysmorphism, developmental delay, atypical tumors, and family history of other genetic disorders including cancers appears as determinants to consider a second genetic etiology and helps to differentiate from an extreme phenotypic spectrum of NF1. Clinicians should have high index of suspicion to exclude coexisting disorders, as apart from providing comprehensive medical care. This also has potential implications in genetic counseling. Long-term effects of the synergistic mechanisms leading to phenotypic complexity and patient outcomes are yet to be characterized, with follow-up needed.

Original languageEnglish (US)
Pages (from-to)911-918
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number3
StatePublished - Mar 2022


  • Down syndrome
  • Prader–Willi syndrome
  • dual diagnosis
  • microdeletion syndrome
  • neurofibromatosis 1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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