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• Letter to the Editor: “Biallelic variants in BRCA1 gene cause a recognizable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency”
  Bruna Lucheze Freire, Thais Kataoka Homma and Alexander Augusto de Lima Jorge
  Published on: 20 August 2021

• Published on: 20 August 2021

  Letter to the Editor: “Biallelic variants in BRCA1 gene cause a recognizable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency”

  • Bruna Lucheze Freire, Research fellow Unidade de Endocrinologia Genética (LIM25), Disciplina de da Faculdade de Medicina da Universidade de São Paulo (FMUSP), Brazil
  • Other Contributors:
    • Thais Kataoka Homma, MD
    • Alexander Augusto de Lima Jorge, Associate Professor

  We appreciate the article by Chirita-Emandi at al (1).
  The authors showed the phenotype of nine patients with biallelic variants at BRCA1 gene associated with Fanconi anemia-like complementation group-S (MIM 617883). As it is a rare syndrome, the publication of articles describing the clinical characteristics and follow-up data are important to improve the knowledge and disseminate evidence-based information.
  In Chirita-Emandi’s article, one patient is first reported and eight are from previous studies. All patients had prenatal and postnatal growth failure, microcephaly, skin pigmentation lesions, facial dysmorphism and cancer family history. Eight presented mild developmental delay, and six had cancer. None presented bone marrow failure or immunodeficiency (1).
  In this letter, we would like to update the clinical case of one of these patients. In a previous article we reported a homozygous loss-of-function BRCA1 mutation in a 2.5-year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features (2). At 6 years-old, she evaluated with neurological symptoms and her skull tomography detected an expansive and infiltrative lesion in the encephalic trunk, compressing and displacing the IV ventricle and obliterating the prepontine cistern and the cerebellar angles. The lesion characteristics were suggestive of diffuse astrocytoma. Soon after a decompressive neurological surgery, this child died....

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  We appreciate the article by Chirita-Emandi at al (1).
  The authors showed the phenotype of nine patients with biallelic variants at BRCA1 gene associated with Fanconi anemia-like complementation group-S (MIM 617883). As it is a rare syndrome, the publication of articles describing the clinical characteristics and follow-up data are important to improve the knowledge and disseminate evidence-based information.
  In Chirita-Emandi’s article, one patient is first reported and eight are from previous studies. All patients had prenatal and postnatal growth failure, microcephaly, skin pigmentation lesions, facial dysmorphism and cancer family history. Eight presented mild developmental delay, and six had cancer. None presented bone marrow failure or immunodeficiency (1).
  In this letter, we would like to update the clinical case of one of these patients. In a previous article we reported a homozygous loss-of-function BRCA1 mutation in a 2.5-year-old girl with severe short stature, microcephaly, neurodevelopmental delay, congenital heart disease and dysmorphic features (2). At 6 years-old, she evaluated with neurological symptoms and her skull tomography detected an expansive and infiltrative lesion in the encephalic trunk, compressing and displacing the IV ventricle and obliterating the prepontine cistern and the cerebellar angles. The lesion characteristics were suggestive of diffuse astrocytoma. Soon after a decompressive neurological surgery, this child died.
  Due to its rarity, we still do not have sufficient data to provide accurate medical management and guidelines protocols related to patients with biallelic BRCA1 variants. However, taking together, seven in eight patients had cancer up to 30 years-old and two of them had solid tumors other than breast or ovarian cancer, indicating the necessity of a closely follow-up and actively searching for malignancy. Nonetheless, further studies and international collaboration are fundamental to understanding the natural history of this disease and to propose appropriate medical recommendations.

  References:

  1. Chirita-Emandi A, Andreescu N, Popa C, Mihailescu A, Riza AL, Plesea R, et al. Biallelic variants in BRCA1 gene cause a recognizable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency. J Med Genet. 2020.

  2. Freire BL, Homma TK, Funari MFA, Lerario AM, Leal AM, Velloso EDRP, et al. Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like phenotype, a clinical report and review of previous patients. Eur J Med Genet. 2018;61(3):130-3.

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  Conflict of Interest:
  None declared.

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