Severe malformations in males from families with osteopathia striata with cranial sclerosis

Abstract

Osteopathia striata with cranial sclerosis (OS‐CS) is a bone dysplasia characterized by longitudinal striations of the long bones and sclerosis of the craniofacial bones. Affected patients show macrocephaly, ocular hypertelorism, frontal bossing, broad nasal bridge and abnormalities of the palate. Anomalies such as hearing loss, congenital heart defect, vertebral anomalies and mental impairment have also been reported. Pedigree analysis has suggested an autosomal dominant inheritance, but a recent report of a family with significantly more affected males than females suggested the possibility of X‐linked inheritance. Here we describe a new family with OS‐CS (the twelfth in the literature) with four affected individuals (two males and two females) spanning three generations. The affected male in the third generation was stillborn with multiple congenital anomalies, whereas the other three affected individuals had mild features. This family may represent another example of X‐linked OS‐CS where the mutated gene(s) is more severe in males.

WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features

“…Facial dysmorphisms include macrocephaly (43%) [2,11-17,19,20,27-32,34,36-39], frontal and occipital bossing (32%) [2,11-15,17,19-21,30-33,36], mandible overgrowth with protuberance of the jaw and dental malocclusion (12%) [2,11,14,23] (giving a leonine appearance), ocular hypertelorism [6,8,10,14,19,20,23,27,29-31,38-40], down-slanting palpebral fissures [19,28,31], low set broad nasal bridge (29%) [1,2,6,8,12,14,15,17,18,20,23,30-32,37,38,41,42], narrow high-arched or cleft palate (Pierre Robin’s triad) (12%) [2,6,8,14-16,19,21,30,31,35] and low set dysplastic ears (9%) [6,12,19,20,29-31,33,39,42]. …”

“…Hearing loss (conductive or mixed type) is the most common neurological manifestation (46%) [1,2,6,8,11,14,16,17,19-23,27,28,30,31,33-38,40,41,43], resulting from narrowing of external auditory canal, impaired mobility of middle ear ossicles, damage to the inner ear or auditory nerve entrapment. Narrowed nerves’ canals and foramina are responsible for nerve encroachment and palsies [1,14,17,19,20,30,31,37-39,41,42].…”

“…patent ductus arteriosus, atrial and ventricular septal defects, valvular and conductive defects) (11%) [8,11,12,14,20,27,29-31,35,37,41,43], respiratory (i.e. laryngotracheomalacia, respiratory distress, nasal obstruction, recurrent bronchitis) (13.5%) [6,13,17,19-21,23,28,30,31,37-39], gastrointestinal (i.e.…”

Ostéochondrodysplasies

“…L'importance de ces déviations rachidiennes n'est pas toujours corrélée à la sévérité de la maladie mais les cyphoscolioses les plus graves se rencontrent surtout dans les formes sévères d'ostéogenèse imparfaite [31] . Les complications neurologiques sont rares [13,19] mais néanmoins possibles [40] . Sur le reste du rachis, une scoliose/ hypercyphose thoracique ou thoracolombaire, une hyperlordose lombaire ou plus rarement, une lordose thoracique peuvent survenir .…”

“…Elle est habituellement asymptomatique mais les formes associées à une ostéocondensation craniofaciale peuvent être source de rétrécissement des foramens nerveux et vasculaires de la base du crâne [40,97,99,155,205] . Elle est habituellement asymptomatique mais les formes associées à une ostéocondensation craniofaciale peuvent être source de rétrécissement des foramens nerveux et vasculaires de la base du crâne [40,97,99,155,205] .…”