Growth failure

Gene: CDKN1C

Green List (high evidence)

IMAGe syndrome is a rare multisystem disorder characterized by intrauterine growth restriction, metaphyseal dysplasia, congenital adrenal hypoplasia, and genital anomalies. Patients with this condition may present shortly after birth with severe adrenal insufficiency, which can be life-threatening if not recognized early and steroid replacement therapy commenced. Other reported features in this condition include hypercalciuria and/or hypocalcemia, craniosynostosis, cleft palate, and scoliosis.

Reported variants are gain-of-function missense on the maternal allele, and are located in a highly-conserved "hot-spot" within the PCNA-binding domain of CDKN1C between codons 272-279. Note 3 families reported with RSS phenotype without other IMAGE features, all with missense changes at amino acid positions 279 and 281.

Note LoF variants in this gene cause overgrowth and BWS.

Created: 6 Aug 2021, 12:26 a.m. | Last Modified: 6 Aug 2021, 12:26 a.m.

Panel Version: 0.16

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)

Phenotypes
IMAGe syndrome, MIM# 614732; Silver-Russell syndrome

Publications

• 22634751
• 33076988
• 31976094
• 31497289

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments