Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects.
This finding underscores the relevance of sequencing ARHGAP31 in similar cases of isolated limb defects, irrespective of the presence of a complete AOS phenotype.
We have generated knockout mice in which only the entire coding region of Fingerin was deleted, and indeed found that most null mice display some limb defects.
Duplication of 5p with breakpoints proximal to band p14 is generally associated with distinct craniofacial malformations, cardiac, renal, intestinal, and limb defects, and mental retardation, whereas duplications with breakpoints distal to 5p14 result in a milder phenotype characterized by minor facial anomalies, developmental delay, and seizures.
Duplication of 5p with breakpoints proximal to band p14 is generally associated with distinct craniofacial malformations, cardiac, renal, intestinal, and limb defects, and mental retardation, whereas duplications with breakpoints distal to 5p14 result in a milder phenotype characterized by minor facial anomalies, developmental delay, and seizures.
Given the expression of the CHD7 gene in the developing limb bud, it was anticipated that limb defects would belong to the spectrum of manifestations of CHARGE syndrome.
Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is a rare autosomal dominant disease caused by heterozygous mutations in the p63 gene and characterized by limb defects, orofacial clefting, ectodermal dysplasia, and ocular defects.
The p63 transcription factor, homolog to the p53 tumor suppressor gene, plays a crucial role in epidermal and limb development, as its mutations are associated to human congenital syndromes characterized by skin, craniofacial and limb defects.
More widespread Dkk1 expression (driven by the Col1A1 3.6 kb promoter) yielded osteopenia with forelimb deformities and hairlessness, while expression restricted to osteoblasts (driven by the Col1A1 2.3 kb promoter) induced severe osteopenia without limb defects or alopecia.
Depending on the type of limb defects, two major groups have been delineated: (1) with predominantly pre-axial anomalies, Nager type AFD, and (2) with predominantly post-axial involvement, Genee-Wiedemann form of AFD, also known as POADS, respectively.
More widespread Dkk1 expression (driven by the Col1A1 3.6 kb promoter) yielded osteopenia with forelimb deformities and hairlessness, while expression restricted to osteoblasts (driven by the Col1A1 2.3 kb promoter) induced severe osteopenia without limb defects or alopecia.
While double knockout of Dlx5 and Dlx6 resulted in limb defects in mice, the majority of patients with SHFM1 had only heterozygous chromosomal abnormalities.
While double knockout of Dlx5 and Dlx6 resulted in limb defects in mice, the majority of patients with SHFM1 had only heterozygous chromosomal abnormalities.
There is no reported instance of a malformed child born to a woman who ingested pure LSD; there are six cases of malformation associated with exposure to illicit LSD, four of which have similar limb defects.
We compared these findings to the differentiation of osteoblasts isolated from a mouse model of ODDD that harbors a germ line Cx43 mutation and exhibits craniofacial and limb defects mimicking human ODDD.