title: Terminal osseous dysplasia with pigmentary defects (TODPD): Follow-up of the first reported family, characterization of the radiological phenotype, and refinement of the linkage region.
abstract: Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies and pigmentary skin defects. We have previously described this syndrome in several females from a large, four-generation pedigree. The presentation in the affected patients included multiple anomalies, hypertelorism, iris colobomas, punched-out pigmentary abnormalities over the face and scalp, brachydactyly, and digital fibromatosis. The phenotype was highly variable thus suggesting that X-inactivation plays an important role in the expression of the disease. Following our initial description of this condition there have been reports of more cases supporting the initial phenotypic description of this disease. We report on the follow-up of this family at about 10 years from the first evaluation. A detailed clinical follow-up and a review of the skeletal surveys suggests that although the most striking features involves the hands and feet, the skeletal involvement is more generalized and affects many other areas. Our previous linkage analysis has demonstrated mapping to Xq27.3-Xq28. Using a 6,056 SNP array, we have further refined the critical region within the Xq28 region. We have also excluded two candidate genes (FLNA and FAM58A) mapping in the critical region. The identification of the gene responsible for this rare condition will shed light on the molecular pathways leading to the various congenital anomalies of TODPD and will allow a more accurate genetic counseling to the affected individuals.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Brunetti-Pierri
authors.forename: Ralph
authors.initials: R
authors.lastname: Lachman
authors.forename: Kwanghyuk
authors.initials: K
authors.lastname: Lee
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Pasquale
authors.initials: P
authors.lastname: Piccolo
authors.forename: Ignatia B
authors.initials: IB
authors.lastname: Van Den Veyver
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
mesh_terms: D001848:Bone Diseases, Developmental / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D002648:Child; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D005532:Foot Deformities, Congenital / Q000150:complications / Q000000981:diagnostic imaging; D008040:Genetic Linkage; D006228:Hand Deformities, Congenital / Q000150:complications / Q000000981:diagnostic imaging; D006801:Humans; D007223:Infant; D010641:Phenotype; D010859:Pigmentation Disorders / Q000150:complications* / Q000000981:diagnostic imaging* / Q000235:genetics; D011859:Radiography