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Case Reports
. 2019 Dec 22:2019:1398250.
doi: 10.1155/2019/1398250. eCollection 2019.

Familial Russell-Silver Syndrome like Phenotype in the PCNA Domain of the CDKN1C Gene, a Further Case

A H Sabir  1 , G Ryan  1 , Z Mohammed  1 , J Kirk  1 , N Kiely  2 , M Thyagarajan  1 , T Cole  1
Affiliations
Case Reports

Familial Russell-Silver Syndrome like Phenotype in the PCNA Domain of the CDKN1C Gene, a Further Case

A H Sabir et al. Case Rep Genet. .

Abstract

We present two half siblings with significant short stature who proved a diagnostic challenge for several years. Radiological findings included subtle epiphyseal changes. The diagnosis was made through whole genome sequencing via the 100,000 genome project. A maternally inherited pathogenic heterozygous CDKN1C variant was found in the PCNA (proliferating cell nuclear antigen) domain. Mutations of the PCNA domain of the CDKN1C gene are known to be associated with IMAGe syndrome thus with adrenal disease, although neither affected patient in our case had evidence of adrenal dysfunction. This report supports the previously reported findings of Russell-Silver syndrome (RSS) like phenotype caused by this unusual mechanism (CDKN1C mutations in the PCNA domain), highlights subtle radiological features not described previously and the phenotypic variability between two affected siblings. Additionally it reminds clinicians of the importance of considering associated adrenal disease/diabetes mellitus for variants within the PCNA domain. Finally it confirms RSS-like disorders should be considered in patients who have epiphyseal or metaphyseal changes and short stature, since CDKN1C PCNA domain mutations can result in this phenotype.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
(a and b) A1 aged 15 years. Facial profile demonstrating prominent forehead, high anterior hairline, and pointed chin.
Figure 2
Figure 2
(a and b) A1 with her maternal half-brother, B1. Note significant short stature (both <0.4th centile). A1 has lumbar lordosis.
Figure 3
Figure 3
(a and b) B1 (aged 21 years) facial front view and profile. Note prominent forehead and high anterior hairline.
Figure 4
Figure 4
(a and b) Radiographs of A1's left hand and left forearm with changes described in the text.
Figure 5
Figure 5
(a and b) B1 radiograph of right hand aged 15 years (a). B1 radiograph of right hand aged 3 years (b).
Figure 6
Figure 6
B1 radiograph of right lower limb (lateral and AP) aged 5 years.
Figure 7
Figure 7
Sanger sequence analysis for A1, B1, and their mother showing nucleotide change C>A, heterozygous.
Figure 8
Figure 8
Focussed pedigree showing CDKN1C gene change; c.836G>T; p.(Arg279Leu) in A1, B1, and their mother.
See this image and copyright information in PMC

References

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