Diagnosis implications of the whole genome sequencing in a large Lebanese family with hyaline fibromatosis syndrome.

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions. METHODS: We describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents. RESULTS: A mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted. CONCLUSIONS: The main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases.

A second family with autosomal recessive spondylometaphyseal dysplasia and early death.

We report on a consanguineous Lebanese family in which two sibs had pre- and post-natal growth retardation, developmental delay, large anterior fontanel, prominent forehead, low-set ears, depressed nasal bridge, short nose, anteverted nares, increased nasal width, prominent abdomen, and short limbs. Radiographs disclosed the presence of wormian bones, platyspondyly, decreased interpedicular distance at the lumbar vertebrae, square iliac bones, horizontal acetabula, trident acetabula, hypoplastic ischia, partial agenesis of the sacrum, ribs with cupped ends, short long bones with abnormal modeling, slight widening of the distal femoral metaphyses, and delayed epiphyseal ossification. Both sibs had a severe cardiomegaly and died at around 24 months from a heart failure. Differential diagnosis suggests that this is a second family presenting a newly described early lethal chondrodysplasia first reported by [Mégarbané et al. (2008); Am J Med Genet Part A 146A:2916-2919].

An unusual case of bilateral primitive obstructed megaureters due to ureteral valves presenting with anuria at the age of 1 month.

Ureteric valves represent a very rare etiology of ureteral obstruction. We experienced an unusual case of bilateral distal ureteric valves that presented as bilateral primitive obstructed megaureters with anuria at the age of 40 days. To our knowledge, this is the second case of bilateral involvement of distal ureteric valves reported in the literature. Bilateral ureteral valves should be included in the differential diagnosis of bladder outlet obstruction, as well as bilateral primitive obstructed megaureters in children. Excision and ureteral reimplantation is curative.