Gracile bones, periostal appositions, hypomineralization of the cranial vault, and mental retardation in brothers: Milder variant of osteocraniostenosis or new syndrome?

Abstract

We report on two brothers with ossification anomalies of membranous and cranial bones, remodeling defect of long bones leading to dense, overtubulated, narrow diaphyses, metaphyseal flare, periostal hyperosotosis that increased during the first months of life, thoracic dystrophy and severe hypotonia. One boy had hypospadias and cleft palate. Follow-up of the surviving boy documented progressive osteopenia, slow healing of the periostal anomalies, liver angiomatosis, mental and motor delay, thoracic deformity, delay in tooth eruption, and progressive microcephaly with enlargement of the cerebral ventricles. This disorder shares some traits with osteocraniostenosis, but lacks the cranial deformity and acromelic micromelia of the latter, in which periostal anomalies are not described. The syndrome reported here may represent a milder form of osteocraniostenosis, or a new entity belonging to the same "family." Genealogical data are consistent with AR or XLR inheritance. No mutations were found in the coding sequence of filamin A.

Clinical and Molecular Diagnosis of Osteocraniostenosis in Fetuses and Newborns: Prenatal Ultrasound, Clinical, Radiological and Pathological Features

“…Overall, whenever prenatal ultrasound was performed, the most prominent clinical features detected were a cloverleaf-shaped skull (11 out of 17 cases with at least one sonography reported), IUGR (15/17 cases), limb undergrowth (16/17 cases) and occasionally intrauterine bone fractures (7/17 cases) [ 3 , 4 , 22 , 23 , 24 , 25 , 26 , 28 , 29 ]. Most of these features were already apparent at 20 weeks of gestation (cfr.…”

Osteocraniostenosis–hypomineralized skull with gracile long bones and splenic hypoplasia. Four new cases with distinctive chondro‐osseous morphology

“…Patients 3 and 4 likely represent much milder cases of osteocraniostenosis but could represent a distinct disorder. Recently, Verloes et al 2005 reported two brothers with radiologic anomalies that included overtubulated long bones with metaphyseal flare and diaphyseal thinning as well as ossification anomalies of membranous and cranial bones and discussed some of the similar findings of these siblings to patients with osteocraniostenosis. The authors suggested autosomal recessive or X‐linked inheritance.…”

Report of a novel variant in the FAM111A gene in a fetus with multiple anomalies including gracile bones, hypoplastic spleen, and hypomineralized skull

“…OCS (OMIM #602361) presents with a more severe, perinatal lethal phenotype characterized by hypomineralized skull frequently resulting in cloverleaf shape, large anterior fontanelle, hypoplastic or absent spleen, and gracile ribs and long bones with wide metaphyses (Costa et al, 1998; Elliott et al, 2006; Puvabanditsin et al, 2016; Spear, 2006; Unger et al, 2013; Verloes et al, 2005). Facial features include prominent forehead, short philtrum and nose, depressed nasal bridge, low‐set ears, midface hypoplasia and small, inverted V‐shape mouth, an ophthalmological abnormalities such as microphthalmia (Beluffi, 2013; Elliott et al, 2006; Puvabanditsin et al, 2016).…”