SNP Shot: Genomic Insights

IMAGe syndrome, a rare condition impacting multiple body systems, is an acronym for a combination of symptoms: intrauterine growth restriction (IUGR), metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies.

Individuals with IMAGe syndrome typically experience slow growth before birth (IUGR) and are small as infants. Skeletal abnormalities, often mild and difficult to detect on x-rays, become noticeable in early childhood. Common bone changes include metaphyseal and epiphyseal dysplasias, which are malformations affecting the ends of long bones in the arms and legs. Some individuals may also develop scoliosis (an abnormal curvature of the spine) or osteoporosis (thinning of the bones).

Adrenal hypoplasia congenita is the most serious aspect of IMAGe syndrome. The adrenal glands, located atop the kidneys, produce vital hormones. Underdevelopment (hypoplasia) of these glands leads to adrenal insufficiency, where insufficient hormone production causes symptoms like vomiting, feeding difficulties, dehydration, hypoglycemia (extremely low blood sugar), and shock, appearing shortly after birth. Without treatment, these complications can be life-threatening.

Genital abnormalities in IMAGe syndrome are exclusively observed in affected males. These include micropenis (an unusually small penis), cryptorchidism (undescended testes), and hypospadias (urethral opening on the underside of the penis).

Additional signs and symptoms can occur in individuals with IMAGe syndrome. Some may have distinctive facial features such as a prominent forehead, low-set ears, and a short nose with a flat nasal bridge. Less frequently, craniosynostosis (premature fusion of skull bones), cleft or bifid uvula (a split in the tissue hanging from the back of the mouth), a high-arched palate, and micrognathia (a small chin) may be present. Other possible features include hypercalcemia (high blood calcium levels), hypercalcuria (high urine calcium levels), and growth hormone deficiency leading to short stature in childhood.

Inheritance:

IMAGe syndrome has a complex inheritance pattern described as autosomal dominant. This means that only one copy of the mutated *CDKN1C* gene in each cell is enough to cause the disorder. However, due to paternal imprinting, IMAGe syndrome only manifests when the mutation is on the copy of the gene inherited from the mother. Mutations on the copy inherited from the father do not cause health issues. Therefore, IMAGe syndrome is only passed down from mothers to their children.