Clinical Guidance

Currently, no genotype-phenotype correlations are known.

Source: GeneReviews — "IMAGe Syndrome"

Penetrance

Although few large pedigrees with IMAGe syndrome have been reported to date, it is clear that the mode of inheritance is autosomal dominant in which only maternal transmission of the imprinted pathogenic variant results in IMAGe syndrome . In one large family of 24 individuals, all seven individuals with IMAGe syndrome inherited the CDKN1C pathogenic variant from their mother. Consistent with the imprinted expression of CDKN1C, unaffected individuals either inherited the pathogenic variant from their father (n=9) or did not have the pathogenic variant (n=8) .

Source: GeneReviews — "IMAGe Syndrome"

Diagnostic Criteria

IMAGe syndrome is an acronym for the major findings in this disorder: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary abnormalities (in males) . No formal clinical diagnostic criteria for IMAGe syndrome have been defined.

Suggestive Findings

IMAGe syndrome should be suspected in individuals with the following clinical, imaging, and suggestive laboratory findings.

Clinical findings

Source: GeneReviews — "IMAGe Syndrome"

Differential Diagnosis

Adrenal Insufficiency

Table 2.

Disorders with Adrenal Insufficiency in the Differential Diagnosis of IMAGe Syndrome

Gene(s) / Genetic Mechanism | DiffDx Disorder | MOI | Clinical Features of DiffDx Disorder

Overlapping w/IMAGe Syndrome | Distinguishing from IMAGe Syndrome

CYP11B1

CYP17A1

CYP21A2

HSD3B2

| Congenital adrenal hyperplasia resulting from: 11-beta hydroxylase deficiency (OMIM 202010); 17-alpha hydroxylase deficiency (OMIM 202110); 21-hydroxylase-deficiency; or 3-beta hydroxysteroid dehydrogenase deficiency (OMIM 201810) | AR | Ambiguous genitalia at birth, adrenal crisis in infancy or childhood | • Infants w/CAH rarely have IUGR.

Source: GeneReviews — "IMAGe Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with IMAGe syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with IMAGe Syndrome

Source: GeneReviews — "IMAGe Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "IMAGe Syndrome"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with IMAGe Syndrome

Source: GeneReviews — "IMAGe Syndrome"