A novel NSDHL variant in CHILD syndrome with gastrointestinal manifestations and localized skin involvement

Mol Genet Genomic Med. 2022 Jan;10(1):e1848. doi: 10.1002/mgg3.1848. Epub 2021 Dec 26.

Abstract

Background: CHILD syndrome is an X-linked dominant disorder associated with pathogenic mutations in the NSDHL gene. The condition is predominantly found in females as it is lethal in males. Most cases present at birth with extensive unilateral ichthyosiform erythroderma involving the trunk and limbs. Milder and less extensive presentations have been reported, leading to misdiagnosis especially during early childhood.

Methods and results: We report an adult female of Malay ancestry who presented with minimal skin and limb involvement. She was only diagnosed in adulthood when she presented with gastrointestinal symptoms and worsening of skin manifestations. The clinical diagnosis was suspected after a combination of clinical, pathological and immunohistochemistry correlation, and molecularly confirmed with the discovery of a frameshift variant in NSDHL. The novel variant was inherited from her mother who had some linear hypopigmented patches over the medial aspects of both her arms and right forearm.

Conclusion: We uncovered a novel frameshift variant associated with presentations that cast a new light on the clinical features of CHILD syndrome.

Keywords: NSDHL; CHILD syndrome; X-linked dominant disorder; ichthyosis; xanthoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases* / genetics
  • Abnormalities, Multiple
  • Adult
  • Female
  • Genetic Diseases, X-Linked* / diagnosis
  • Genetic Diseases, X-Linked* / genetics
  • Genetic Diseases, X-Linked* / pathology
  • Humans
  • Ichthyosiform Erythroderma, Congenital* / genetics
  • Limb Deformities, Congenital* / diagnosis
  • Limb Deformities, Congenital* / genetics
  • Limb Deformities, Congenital* / pathology

Substances

  • 3-Hydroxysteroid Dehydrogenases
  • Nsdhl protein, human

Supplementary concepts

  • Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects