Costello syndrome with severe cutis laxa and mosaic HRAS G12S mutation

Katta M. Girisha, Leslie E. Lewis, Shubha R. Phadke, Kerstin Kutsche

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Costello syndrome is a rare developmental disorder characterized by coarse face, postnatal growth retardation, skin and musculoskeletal anomalies, cardiovascular abnormalities, mental retardation, and tumor predisposition. Dermatological manifestations usually include redundant, soft and thickened skin. Loose skin is especially present over the neck, hands, and feet. Heterozygous missense mutations in HRAS are causative for Costello syndrome, with the c.34G > A (p.G12S) mutation as the most commonly found alteration. In the majority of affected individuals pathogenic sequence changes appeared de novo, however, two individuals with somatic mosaicism for the HRAS mutation have been reported. Here, we describe a boy with somatic mosaicism for the c.34G > A mutation in HRAS. Allelic quantitation revealed the mutation in approximately 58% of his lymphocytes; however, in DNA derived from buccal cells we could not detect the sequence change. The patient presented with the typical clinical findings of Costello syndrome such as increased birth weight, severe failure to thrive, characteristic facial appearance, and skin abnormalities. The dermatological anomalies were remarkable as he showed severe skin laxity with wrinkling of skin on all parts of the body due to loss of subcutaneous fat that decreased significantly by age 13 months. This case further adds to the phenotypic variability seen in patients with somatic mosaicism for an HRAS mutation and highlights the awareness of mosaic mutations in Costello syndrome when molecular testing is performed.

Original languageEnglish
Pages (from-to)2861-2864
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number11
DOIs
Publication statusPublished - 11-2010

Fingerprint

Costello Syndrome
Cutis Laxa
Mutation
Mosaicism
Skin
Skin Abnormalities
Cardiovascular Abnormalities
Skin Aging
Failure to Thrive
Cheek
Subcutaneous Fat
Missense Mutation
Human Body
Birth Weight
Intellectual Disability
Foot
Neck
Hand
Lymphocytes
DNA

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Genetics

Cite this

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abstract = "Costello syndrome is a rare developmental disorder characterized by coarse face, postnatal growth retardation, skin and musculoskeletal anomalies, cardiovascular abnormalities, mental retardation, and tumor predisposition. Dermatological manifestations usually include redundant, soft and thickened skin. Loose skin is especially present over the neck, hands, and feet. Heterozygous missense mutations in HRAS are causative for Costello syndrome, with the c.34G > A (p.G12S) mutation as the most commonly found alteration. In the majority of affected individuals pathogenic sequence changes appeared de novo, however, two individuals with somatic mosaicism for the HRAS mutation have been reported. Here, we describe a boy with somatic mosaicism for the c.34G > A mutation in HRAS. Allelic quantitation revealed the mutation in approximately 58{\%} of his lymphocytes; however, in DNA derived from buccal cells we could not detect the sequence change. The patient presented with the typical clinical findings of Costello syndrome such as increased birth weight, severe failure to thrive, characteristic facial appearance, and skin abnormalities. The dermatological anomalies were remarkable as he showed severe skin laxity with wrinkling of skin on all parts of the body due to loss of subcutaneous fat that decreased significantly by age 13 months. This case further adds to the phenotypic variability seen in patients with somatic mosaicism for an HRAS mutation and highlights the awareness of mosaic mutations in Costello syndrome when molecular testing is performed.",
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Costello syndrome with severe cutis laxa and mosaic HRAS G12S mutation. / Girisha, Katta M.; Lewis, Leslie E.; Phadke, Shubha R.; Kutsche, Kerstin.

In: American Journal of Medical Genetics, Part A, Vol. 152, No. 11, 11.2010, p. 2861-2864.

Research output: Contribution to journalArticle

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