IMAGe syndrome
IMAGe syndrome is a rare genetic disorder characterized by a specific combination of growth, skeletal, adrenal, and genital abnormalities.
Overview
The acronym IMAGe stands for the combination of intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies. This rare syndrome affects multiple systems throughout the body.
Symptoms
- Intrauterine growth restriction: Affected individuals typically grow slowly before birth and remain small during infancy.
- Skeletal abnormalities: Common findings include metaphyseal dysplasia and epiphyseal dysplasia (malformations of the ends of long bones). Some individuals also experience abnormal side-to-side curvature of the spine or thinning of the bones.
- Adrenal hypoplasia congenita: This is the most severe feature. Underdevelopment of the adrenal glands leads to adrenal insufficiency, which can cause vomiting, feeding difficulties, dehydration, hypoglycemia, and shock shortly after birth.
- Genital anomalies: Occurring only in males, these include an unusually small penis (micropenis), undescended testes (cryptorchidism), and hypospadias.
- Additional features: Some individuals exhibit distinctive facial features, premature fusion of skull bones (craniosynostosis), a split in the soft tissue at the back of the mouth, high levels of calcium in the blood or urine, and short stature due to growth hormone deficiency.
Causes
IMAGe syndrome is caused by mutations in the CDKN1C gene, which provides instructions for a protein that regulates growth before birth. These mutations alter the protein's structure and function, inhibiting normal development. The condition is influenced by genomic imprinting, a process where the activity of a gene depends on which parent it was inherited from. The CDKN1C gene is primarily active when inherited from the mother.
Inheritance
The condition follows an autosomal dominant inheritance pattern, meaning one altered copy of the gene is sufficient to cause the disorder. However, because the gene is paternally imprinted (the copy from the father is normally inactive), the syndrome only manifests when the mutation is present on the maternally inherited copy. Consequently, IMAGe syndrome is passed only from mothers to their children.