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. 2018 Feb;176(2):465-469.
doi: 10.1002/ajmg.a.38581. Epub 2017 Dec 19.

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

Laura S Farach  1 , Mary E Little  2 , Angela L Duker  2 , Clare V Logan  3 , Andrew Jackson  3 , Jaqueline T Hecht  4 , Michael Bober  2
Affiliations

The expanding phenotype of RNU4ATAC pathogenic variants to Lowry Wood syndrome

Laura S Farach et al. Am J Med Genet A. 2018 Feb.

Abstract

RNU4ATAC pathogenic variants to date have been associated with microcephalic osteodysplastic primordial dwarfism, type 1 and Roifman syndrome. Both conditions are clinically distinct skeletal dysplasias with microcephalic osteodysplastic primordial dwarfism, type 1 having a more severe phenotype than Roifman syndrome. Some of the overlapping features of the two conditions include developmental delay, microcephaly, and immune deficiency. The features also overlap with Lowry Wood syndrome, another rare but well-defined skeletal dysplasia for which the genetic etiology has not been identified. Characteristic features include multiple epiphyseal dysplasia and microcephaly. Here, we describe three patients with Lowry Wood syndrome with biallelic RNU4ATAC pathogenic variants. This report expands the phenotypic spectrum for biallelic RNU4ATAC disorder causing variants and is the first to establish the genetic cause for Lowry Wood syndrome.

Keywords: Lowry Wood syndrome; RNU4ATAC; epiphyseal dysplasia; microcephaly; skeletal dysplasia.

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Figures

FIGURE 1
FIGURE 1
Sloping forehead, prominent nose, and full lips are present in all patients: patient 1 (a and b), patient 2 (c), and patient 3 (d). Representative X-rays demonstrate generalized epiphyseal dysplasia and normal vertebrae, consistent with MED. Findings include mild epiphyseal dysplasia and brachyclinodactyly V (f); epiphyseal dysplasia of the femoral heads, distal femur, and proximal and distal tibia (g); epiphysealdysplasia, shallow acetabula, dislocated femoral heads, and coxa valga (h); and normal vertebrae (e).
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