Oculo-auriculo-vertebral spectrum with craniosynostosis and osteo-cartilagineous multiple defects: a diffuse chondro-membranous-osteo-dysplasia

Abstract

We report on a female with oculo-auriculo-vertebral spectrum, low height, and on X-ray lambdoid suture synostosis, cerebral cyst/mild holoprosencephalia and cholesteatoma, and multiple abnormalities of bones of chondral origin. On the right side, maxillary, mandibular bones, external auditory canal, middle ear were hypoplastic as well as semicircular canal, cranial base, bones vestibule. On the left side, coclea, timpanic cavity, mastoid antrum were hypoplastic, while stapes was misshapen. Limbs bones were slender with thin metaphyses and some carpal bones were absent. Hand second phalanx was hypoplastic and fifth finger presented clynodactily. Lambdoid synostosis expressed membranous ossification abnormality. We hypothesize that during the blastogenesis a mutation of a factor responsible for abnormal generalized endochondral and connectival ossification (possibly fibroblast growth factor receptor) occurs. IntroductionOculo-auriculo-vertebral spectrum (OAVS) 1,2 is charachterized by hemifacial hypoplasia, eye, auricular and vertebral defects, and hypoplasia of soft and bony tissues, mainly in the face widespread to many other tissues. The pathogenesis of this condition is complex due to external and genetic causes; many cases are sporadic, but familial instances are also reported. Phenotypes of OAVS are variable and incomplete formsare common.We report on a patient with OAVS, low height and weight, multiple cerebral malformations, synostosis of lambdoidal suture cartilage, and bone multiple defects demonstrated by X-ray, for which we hypothesized a congenital diffuse chondro-osteodysplasia. Case ReportThe aunt of the proposita presented hemifacial microsomia, bilateral stenosis of external auditory canal, and middle ear cholesteatoma. During gestational age, her mother suffered from anemia, gastritis and colitis, while her father was exposed to toxic agents. It was her mother's first pregnancy. The following pregnancy ended in aborted fetus with multiple anomalies and semilobar holoprosencephaly. The proposita, born at term, presented a birth weight of 1850 g, length was 36.7 cm, head circumference 27.5 cm (all below the third percentile).Physical examination showed cranio-facial asymmetry, right hemifacial microsomia, brachyplagiocephaly, right parietal bossing, micrognathia, ocular hypotelorism, upslanting palpebral fissures with epicanthus, left exotropia, bilateral malformed ears with narrow right external auditory canal, pigmentation of the retina. Feet and hands were small, with flexion and clynodactily of all fingers; muscular hypotonia and hypotrophy were present. At sonography, heart, liver, spleen, kidney, ureters and bladder were normal. Skull X-ray demonstrated craniosynostosis of coronal and (partial) lambdoid sutures. Computed tomography (CT) scan demonstrated a large area, filled with cerebrospinal fluid, communicating with lateral ventricles in the fronto-parieto-occipital region, a condition confirmed at 1 year of life, when magnetic resonance imaging (MRI) showed partial agenesis of the...