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Review
. 2021 Jun;9(6):e1690.
doi: 10.1002/mgg3.1690. Epub 2021 May 1.

Costello syndrome with special cutaneous manifestations and HRAS G12D mutation: A case report and literature review

Wen Qian  1 , Meijie Zhang  2 , Hequn Huang  3 , Yihe Chen  1 , Gajin Park  1 , Ni Zeng  1 , Yueyue Li  1 , Qian Lu  1 , Dan Luo  1
Affiliations
Review

Costello syndrome with special cutaneous manifestations and HRAS G12D mutation: A case report and literature review

Wen Qian et al. Mol Genet Genomic Med. 2021 Jun.

Abstract

Background: Costello syndrome (CS, OMIM 218040) is a rare congenital disorder caused by mutations in HRAS. Previous studies reported that approximately 80% of patients with CS share the same pathogenic variant in HRAS gene in c.34G> A (p.G12S). Here, we report a CS patient with c.34G> A (p.G12D) variant in HRAS gene and she presented with special manifestation.

Methods and results: We describe a 31-year-old female patient who presented with distinctive facial appearance, intellectual disability, dental abnormalities, hyperkeratosis of palmer and planter, loose skin at birth, papillomata on the face and nipples. The whole-exome sequencing (WES) technology provided by Haotian Biotechnology (China) confirmed p.G12D variant in HRAS gene. To elucidate the typical features of CS with p.G12D variant, we further reviewed these previously reported cases and found that patients with G12D variant died within three months after birth due to multiple organ failure. They had the typical facial characteristics, failure to thrive, skin and cardiac abnormalities, and gene testing confirmed the diagnosis of CS.

Conclusion: To the best of our knowledge, this is the first article to report a patient with a p.G12D variant that had special but mild manifestation. Moreover, this report and literature review casts new light on the clinical features of p.G12D variant.

Keywords: Costello syndrome; HRAS variant; heterozygous variants; p.G12D.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Clinical appearance of patient. (a) She had papillomata on the face and teeth dysplasia. (b,c) Mottled pigmentation was observed all over the body with clear boundaries. (d,e,f) Palmoplantar keratosis was also seen
FIGURE 2
FIGURE 2
An oral panoramic CT showed that the alveolar bone was absorbed and damaged in different degrees
FIGURE 3
FIGURE 3
The results of the whole‐exome sequencing. The whole‐exome sequencing confirmed the variant of exon2: c.35G>A: p.G12D in the patient but not in her parents and sister, confirming the heterozygous mutation
See this image and copyright information in PMC

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