Early Diagnosis and Follow-Up of a Novel Homozygous Mutation in SOST Gene in a Child with Recurrent Facial Palsy: A Case Report and Review of the Literature

Abstract

Recurrent facial palsy is a rare event in the pediatric population, mostly idiopathic or associated with common comorbidities or, rarely, observed in syndromic conditions. However, some cases are difficult to explain and need more accurate diagnostic approaches. In this work, we describe a pediatric case of recurrent facial palsy secondary to hyperostosis of the skull and narrowing of the neural foramina related to a SOST-related sclerosing bone dysplasia. To our knowledge, this is the first Italian case that is also related to a novel loss-of-function variant in the SOST gene. We highlight the clinical relevance of a proper early diagnosis and the need for correct monitoring of the clinical evolution, considering the natural history of the disease, to prevent/reduce severe neurological complications.

Keywords: SOST; SOST-related sclerosing bone dysplasia; recurrent facial palsy.

Figure 1

Proband at 3 (upper panel) and 4 years (lower panel). See also Supplementary Table S1.

Figure 2

(A). Three-generation pedigree. Filled black symbols indicate the individuals affected with Sclerosteosis, and the shapes partially filled indicate the carriers with heterozygous mutation. The proband is marked with the arrow. (B). Schematic representation of Sclerosteosis-relevant mutations reported ClinVar pathogenic mutations in SOST gene (see also Supplementary Table S2). The new mutations are boxed in the rectangle. (C). Sanger sequencing results of SOST gene variant c.71delA (p.Gln24ArgfsTer33) in the proband (homozygous) and her heterozygous parents. The arrow indicates the position of mutation. (D). SOST model (AF-Q9BQB4-F1-model_v4, SWISS Model Repository) and focus on Gln24 substitution, in bold.

Figure 3

(A). Brain CT (a,b) and MRI (c,d) show sclerosis and hyperostosis with thickening of the cranial theca and basicranium. Arrows indicate the reduction in the caliber of optic foramina and internal acoustic canals (e,f). Spine MRI (g,h) reveals diffuse and mild sclerosis of vertebra both in T1W and T2W. (B). X-ray bone survey shows generalized increase in bone density with diffuse cortical thickening, showed in different sections (a,b,c,d). (C) Five-year follow-up coronal MRI with 3D-DRIVE sequences shows severe stenosis of internal acoustic canals (b) compared to baseline MRI (a). (D). Five-year follow-up CT (a,b) compared to baseline study (c,d) demonstrates progressive increase of hyperostosis and thickening of the cranial theca and temporal bones with severe stenosis of internal acoustic canals (arrows).