Diagnostic Criteria

Where no specific reference is cited, data came from the Primordial Dwarfism Registry (NCT04569149).—ED. No consensus clinical diagnostic criteria for RNU4atac-opathy have been published.

Suggestive Findings

RNU4atac-opathy should be suspected in individuals with a combination of the following clinical and radiographic findings and family history.

Clinical findings

Source: GeneReviews — "RNU4atac-opathy"

Differential Diagnosis

The differential diagnosis of RNU4atac-opathy depends on presenting features and the severity of the findings on the phenotype spectrum. While the differential diagnosis can be narrowed for individuals with a severe phenotype, the differential diagnosis for individuals with milder growth restriction and skeletal dysplasia is extensive; thus, all genes known to be associated with the primary clinical finding (e.g., microcephaly/ skeletal dysplasia/ retinal dystrophy/ immunodeficiency) should be considered. Growth Restriction When growth restriction is extreme (occipitofrontal circumference and height 4 SD below the mean), the differential diagnosis is the same as for other forms of microcephalic dwarfism (see Microcephalic Osteodysplastic Primordial Dwarfism Type II, Differential Diagnosis). Brain malformations and skeletal features are significant discriminants in individuals with extreme growth restriction and may allow for a clinical/syndromic diagnosis of RNU4atac-opathy. Milder growth restriction has a wider differential, in which either skeletal dysplasia, retinal dystrophy, and/or immunodeficiency may provide diagnostic prompts. Skeletal Dysplasia Epiphyseal dysplasia (with or without spondylo/metaphyseal involvement) alongside microcephaly should be strongly discriminant for RNU4atac-opathy with a limited differential diagnosis, particularly if immunodeficiency and/or retinal dystrophy is also present . Individuals with RNU4atac-opathy do not always have microcephaly; therefore, absence of this clinical feature does not exclude the diagnosis. Table 7. Skeletal Dysplasias Associated with Microcephaly in the Differential Diagnosis of RNU4atac-opathy

Management Guidelines

No clinical practice guidelines for RNU4atac-opathy have been published. The recommendations in this section are based on the authors' experience in caring for 20 individuals over almost 20 years. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with RNU4atac-opathy, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 8. RNU4atac-opathy: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "RNU4atac-opathy"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations listed in are recommended. Table 10. RNU4atac-opathy: Recommended Surveillance

Source: GeneReviews — "RNU4atac-opathy"