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Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Other conditions with mesoaxial polydactyly : oral-facial-digital syndrome type 6: autosomal recessive condition, with hypertelorism, median cleft lip and palate, lingual cleft with nodules, teeth abnormalities, multiple frenula, midline brain malformation (absence of olfactory bulbs and tracts, semilobar holoprosencephaly, absence or dysgenesis of the cerebellar vermis, corpus callosum, hypothalamus and pituitary gland), retinal dystrophy, congenital heart defects, renal agenesis, short stature, mental retardation. McKusick-Kaufman syndrome: triad of hydrometrocolpos or male genital malformations, postaxial or mesoaxial polydactyly, and cardiac malformations. Caused by recessive mutations in the gene MKKS; more frequent in the Amish population. Some overlap with Bardet-Biedl syndrome. Chondroectodermal dysplasia (Ellis-van Creveld) (p. 167).
The Human Genome Project and Its Impact on Understanding Developmental Disabilities
Published in Merlin G. Butler, F. John Meaney, Genetics of Developmental Disabilities, 2019
Daniel J. Wattendorf, Maximilian Muenke
In 2000, another subset of BBS patients (representing the sixth of currently eight known loci for this disease, BBS1-BBS8) was found to have mutations in a gene known to cause another disease, McKusick-Kaufman syndrome (18,19). McKusick-Kaufman syndrome is characterized primarily by congenital heart defects, postaxial polydactlyly, and hydrometrocolpos (i.e., accumulation of fluids in the uterus and vagina) in affected females (20), but is caused by mutation in the same gene. In other words, different alleles of this gene can cause two entirely different disease phenotypes. The success of positional cloning and the acquisition of the sequence of the clones allowed more comprehensive analysis of inheritance mechanisms and illustrated even more diverse mechanisms of inheritance. Evaluation of pedigrees that contained mutations in BBS6 showed affected individuals that contained only one mutant allele. Molecular testing of another cloned gene, BBS2, in the same pedigrees identified cases with two mutant alleles. Further analysis of pedigrees segregating with BBS2 showed affected individuals with a single BBS2 mutant allele and two BBS6 mutant alleles. Multiple alleles at different loci appeared to cause BBS in these families. Furthermore, individuals were found within these pedigrees that had two mutant alleles at one locus and two wild-type (i.e., normal) alleles at the other locus, yet were unaffected (15). This representation of digenic inheritance causing a developmental disorder would not have been feasible if all of these families were grouped together as part of a large positional cloning study that was typically required prior to the availability of dense genetic maps provided by the HGP. Even more complex positional cloning efforts are now possible.
Value of Placental Examination in the Diagnostic Evaluation of Stillbirth
Published in Fetal and Pediatric Pathology, 2022
The fetal causes (14/147 cases, 9%) encompassed chromosomal and non-chromosomal malformations which included those of the central nervous system (hydrocephalus, type II Chiari malformation, vein of Galen aneurysmal dilation), McKusick-Kaufman syndrome, lethal polymalformative syndrome associated with chromosomal aberration (trisomy 18, two cases) or strongly suspected to be chromosomal disorder (not cytogenetically investigated, eight fetuses, 5%) because of the characteristic placental histologic features of aneuploidy. The aneuploid placental villi displayed an important immaturity with a thickened layer of trophoblast and hypovascular reticular stroma. Their contours were typically very irregular delineating deep invaginations, and their stromal axis showed central cystic spaces and pseudo-rosettes.