Disease relevance of Dysostoses

• Mutations in genes encoding Notch pathway components underlie three inherited human diseases: Alagille syndrome, spondylocostal dysostosis, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [1].
• The similarity in the phenotypes we describe here and that of some human birth defects, such as spondylocostal dysostosis, raises the possibility that mutations in Tbx6 or components of this pathway may be responsible for these defects [2].
• The disorder is characterized by frontonasal dysostosis, coronal craniostenosis, and the variable presence of other skeletal defects, including short webbed neck, sloping shoulders, polydactyly, syndactyly, and broad first toes [3].
• Conditions treated were facial cleft (n = 5), frontonasal dysplasia (n = 7) and facial dysostosis (n = 8).Intra-operative complications included major haemorrhage (n = 4), bradycardia (n = 3) and unintentional tracheal extubation (n = 1) [4].
• A particular middle phalangeal type of ASPs is found in a distinct variety of multiple epiphyseal dysplasia with marked retardation of bone age and severe coxarthrosis in adult life, previously reported as "hereditary peripheral dysostosis" [Bachman, 1967: Proc R Soc Med 60:21-22; Giedion, 1969: Fortschr Rontgenstr 110:507-524] [5].

Psychiatry related information on Dysostoses

• Biemond syndrome type 2 (BS2) is classically regarded as a recessively inherited condition (MIM 210350) comprising mental retardation, coloboma, obesity, polydactyly, hypogonadism, hydrocephalus, and facial dysostosis [6].

High impact information on Dysostoses

• Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis [7].
• Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis [8].
• Spondylocostal dysostosis (SD, MIM 277300) is a group of vertebral malsegmentation syndromes with reduced stature resulting from axial skeletal defects [7].
• Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis [9].
• Mutated MESP2 causes spondylocostal dysostosis in humans [10].

Chemical compound and disease context of Dysostoses

• The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1 [11].
• Finally, although the facial anomalies produced by retinoic acid resemble the human mandibulo-facial dysostosis syndrome, no correlation was found between hemicraniofacial microsomia and the administration of methyl-triazene [12].
• In children, occlusal problems and orofacial dysfunctions caused by maxillonasal dysostosis should be treated as soon as possible with an orthodontic mask [13].
• The metaphyseal dysostosis matrix is uniformly alcian blue positive at all molarities of MgCl2 up to 1.0 M [14].
• Carbohydrate-deficient glycoprotein syndrome type I: a new cause of dysostosis multiplex [15].

Biological context of Dysostoses

• Cartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity [16].
• Prenatal sonographic features of spondylocostal dysostosis and diaphragmatic hernia in the first trimester [17].
• The administration of 400 mg/kg 13 cis-retinoic acid (RA) to pregnant C57BL mice on day 9 of gestation produced anomalies of the cephalic extremity in the embryos resembling human mandibulo-facial dysostosis [12].

Anatomical context of Dysostoses

• Campomelic syndrome (or campomelic dysostosis, CD; MIM *114290) is an autosomal dominant skeletal malformation syndrome characterized by shortness and bowing of long bones, especially of the lower limbs [18].
• The metaphyseal dysostosis growth plate matrix was examined by alcian blue-magnesium chloride histochemistry and electron microscopy [14].

Gene context of Dysostoses

• Dynamic expression patterns of the pudgy/spondylocostal dysostosis gene Dll3 in the developing nervous system [19].
• This examination suggested that mutations at the PRRX1 and/or PRRX2 loci could result in Nager Acrofacial Dysostosis (NAFD) syndrome [20].
• Acrofacial dysostosis in a patient with the TSC2-PKD1 contiguous gene syndrome [21].
• A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis [22].
• The map location and expression pattern suggest ZFP-37 as a candidate gene for a craniofacial-limb malformation, Nager syndrome (acrofacial dysostosis) [23].

Analytical, diagnostic and therapeutic context of Dysostoses

• The whole clinical picture of the present patient suggests a 'new' type of frontonasal dysplasia and main differential diagnosis includes the acrofrontofacionasal dysostosis 2 syndrome (MIM 201181) [24].
• Animal models of hemifacial microsomia and thalidomide-induced otomandibular dysostosis are described; the causal mechanism of malformation appeared to be closely related to the formation of a hematoma at the time of development of the stapedial arterial systems [25].

References