Roifman syndrome
A rare recessive disorder of short stature, antibody deficiency, retinal disease and developmental delay, caused by a gene that makes RNA, not protein.
What it is
An autosomal recessive disorder caused by variants in RNU4ATAC, a gene for a small RNA of the minor spliceosome; it belongs to the RNU4ATAC spectrum with microcephalic osteodysplastic primordial dwarfism type I and Lowry–Wood syndrome.
Who gets it
Very rare; a few dozen people have been reported worldwide.
Causes
- Biallelic variants in RNU4ATAC, which encodes the U4atac small nuclear RNA
- Autosomal recessive inheritance
Pathophysiology
About 1 in 200 human introns is removed by a separate «minor» spliceosome. U4atac RNA is part of it; when it is faulty, minor introns are spliced poorly in many genes, which disturbs bone growth, B-cell function and retinal and brain development.
Symptoms and signs
- Short stature with a spondyloepiphyseal dysplasia (spine and growth-plate changes)
- Recurrent infections from antibody deficiency
- Retinal dystrophy
- Developmental delay or learning difficulty
- Distinctive facial features
Diagnosis
- Clinical
- Suspected when short stature with skeletal dysplasia combines with antibody deficiency and retinal disease.
- Tests
- Immunoglobulin levels and vaccine responses; sequencing of RNU4ATAC. Because RNU4ATAC is a non-coding gene, standard exome capture can miss it, so it must be included specifically or found by genome sequencing.
- Imaging
- Skeletal X-rays show the spondyloepiphyseal changes.
Treatment
- Medical
- Immunoglobulin replacement to prevent infections.
- Follow-up
- Eye, growth, immune and developmental follow-up.
- Rehabilitation
- Educational and therapy support for developmental needs.
Complications
- Recurrent infections
- Progressive visual loss from retinal dystrophy
Prognosis
Depends mostly on control of infections and on the degree of developmental and visual involvement.
Test yourself
Think of the answer, then tap the question to see it.
What is unusual about the gene behind Roifman syndrome?
RNU4ATAC makes a small RNA of the minor spliceosome, not a protein.
Why can a standard exome miss Roifman syndrome?
RNU4ATAC is non-coding, so exome capture designed for protein-coding exons may not include it.
Which treatment prevents the main complication?
Immunoglobulin replacement, which prevents infections from the antibody deficiency.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: RNU4atac-opathy (GeneReviews (NCBI Bookshelf), 2023); Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing (Nature Communications (Merico D et al.), PubMed 26522830, 2015).
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Representative model, for educational purposes only.