Precocious puberty and anal stenosis in an African patient with Rothmund-Thomson syndrome

Am J Med Genet A. 2023 Jan;191(1):280-283. doi: 10.1002/ajmg.a.62980. Epub 2022 Sep 26.

Abstract

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a rash that progresses to poikiloderma. Other common features include sparse hair, eyelashes and eyebrows, short stature, variable skeletal abnormalities, dental defects, cataracts, hypogonadism, and an increased risk for cancer, especially osteosarcoma and skin cancer. RTS is caused by biallelic pathogenic variants in ANAPC1 (Type 1 RTS) or RECQL4 (Type 2 RTS). We present an African girl with Type 2 RTS caused by a nonsense variant and an intronic variant in RECQL4. The patient presented precocious puberty, which has not been previously reported in RTS and that was treated with a GnRH analog, and anal stenosis, which has only been reported once. This case highlights the need to consider deep intronic variants in patients with RTS when pathogenic variants in the coding regions and exon/intron boundaries are not identified and expands the phenotypic spectrum of this disorder.

Keywords: RECQL4; Rothmund-Thomson syndrome; anal stenosis; intronic variant; poikiloderma; precocious puberty.

Publication types

  • Case Reports

MeSH terms

  • Bone Neoplasms*
  • Constriction, Pathologic
  • Female
  • Humans
  • Mutation
  • Osteosarcoma*
  • Puberty, Precocious* / genetics
  • RecQ Helicases / genetics
  • Rothmund-Thomson Syndrome* / pathology
  • Rothmund-Thomson Syndrome* / therapy

Substances

  • RecQ Helicases