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To date less than 20 cases have been reported worldwide in the scientific and medical literature.

Roifman syndrome is characterized by pre- and post-natal growth retardation, hypotonia, borderline to moderate intellectual disability, retinal dystrophy, spondyloepiphyseal dysplasia (epiphyseal dysplasia, epiphyses ossification delay, vertebral changes) and skeletal anomalies (brachydactyly, fifth finger clinodactyly), as well as humoral immunodeficiency, characterized by inability to generate specific antibodies and low circulating B-cells, suggestive of a partial block of B-cell proliferation and maturation. Craniofacial dysmorphism typically includes microcephaly, narrow palpebral fissures, prominent and long eyelashes, a narrow, tubular, upturned nose with hypoplastic alae nasi, long philtrum and thin upper lip. Eczema and mild limitation in hip flexion may be observed. One instance of hypogonadotrophic-hypogonadism and one instance of myocardial noncompaction were reported.

Roifman syndrome is caused by bi-allelic mutations of RNU4ATAC (2q14.2), a gene encoding a small nuclear RNA involved in minor (U12) splicing. At least one mutation locates in the stem II region of RNU4ATAC. Mutations in the same gene also cause Taybi-Linder syndrome, a more severe disorder in which there are many overlapping features.

Diagnosis is suggested based on the clinical, immune and radiological phenotype and confirmed by RNU4ATAC sequencing.

Other syndromes that combine immunodeficiency and skeletal aberrations may be considered and include cartilage hair hypoplasia, primary bone dysplasias with micromelia, severe combined immunodeficiency due to adenosine deaminase deficiency, and Schimke immune-osseous dysplasia.

There have been no reports of prenatal diagnosis to date.

Roifman syndrome is transmitted as an autosomal recessive trait. Genetic counseling should be offered to at risk families (where each parent is an unaffected carrier) informing them that there is a 25% risk of having an affected child at each pregnancy.

Treatment is supportive only. Particular attention should be given to susceptibility to infections, growth and psychomotor development. Medical care and management should be provided according to recurrent infections and intellectual disability.

Prognosis appears to be good with no reported limitation of life expectancy. Infections can be severe and recurrent (pneumonia, septicemia, recurrent herpes reactivation, etc.).