Terminal transverse limb defects with “nubbins”

We present a case of unilateral terminal transverse forearm deficiency with subterminal digit-like nubbins, identified in a fetus from a pregnancy terminated electively in the second trimester because the distal right arm and hand could not be seen by ultrasound and were presumed to be absent. Pathologic evaluation showed distal transverse shortening, tapering to a point in the mid-forearm. Five primitive digital nubbins were present, located just proximal to the tapered point. The arm vessels appeared normal histologically, and the amnion showed no evidence of intrauterine disruption. Histologic examination of the nubbins revealed osteocartilaginous tissue, never described previously within digital nubbins. This fetus has the rare phenotype of terminal transverse limb defects with residual nubbins, but differs in that the nubbins are not at the tip of the terminal transverse limb defect.

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Epidemiological Association of Cannabinoid- and Drug- Exposures and Sociodemographic Factors with Limb Reduction Defects Across USA 1989-2016: A Geotemporospatial and Causal Inference Study

10.1101/2020.09.01.20186163 ◽

2020 ◽

Author(s):

Albert S Reece ◽

Gary Kenneth Hulse

Keyword(s):

Causal Inference ◽

Robust Regression ◽

Relative Risk Reduction ◽

Sociodemographic Factors ◽

Cannabis Use ◽

Human Populations ◽

Limb Defects ◽

Live Births ◽

Limb Reduction ◽

Epidemiological Association

Reports of major limb defects after prenatal cannabis exposure (PCE) in animals and of human populations in Hawaii, Europe and Australia raise the question of whether the increasing use of cannabis in USA might be spatiotemporally associated with limb reduction rates (LRR) across USA. Geotemporospatial analysis conducted in R. LRR was significantly associated with cannabis use and THC potency and demonstrated prominent cannabis-use quintile effects. In final lagged geospatial models interactive terms including cannabinoids were highly significant and robust to adjustment. States in which cannabis was not legalized had a lower LRR (4.28 v 5.01 /10,000 live births, relative risk reduction = -0.15, (95%C.I. -0.25, -0.02), P=0.021). 37-63% of cases are estimated to not be born alive; their inclusion strengthened these associations. Causal inference studies using inverse probabilty-weighted robust regression and e-values supported causal epidemiological pathways. Findings apply to several cannabinoids, are consistent with pathophysiological and causal mechanisms, are exacerbated by cannabis legalization and demonstrate dose-related intergenerational sequaelae.

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Human tail and limb defects: A short tale of a long tail

Muller Journal of Medical Sciences and Research ◽

10.4103/0975-9727.146477 ◽

2015 ◽

Vol 6 (1) ◽

pp. 92

Author(s):

BalikeKrishna Praveen ◽

Kallekkattu Dipu

Keyword(s):

Long Tail ◽

Limb Defects ◽

Human Tail

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Association of hereditary thrombocythemia and distal limb defects with a thrombopoietin gene mutation

Blood ◽

10.1182/blood-2009-04-217851 ◽

2009 ◽

Vol 114 (8) ◽

pp. 1655-1657 ◽

Cited By ~ 14

Author(s):

Claudio Graziano ◽

Simona Carone ◽

Emanuele Panza ◽

Flora Marino ◽

Pamela Magini ◽

...

Keyword(s):

Human Development ◽

Gene Mutation ◽

Autosomal Dominant ◽

Specific Gene ◽

Autosomal Dominant Disorder ◽

Distal Limb ◽

Limb Defects ◽

First Report

Abstract Hereditary thrombocythemia is a rare autosomal dominant disorder caused by mutations in either the thrombopoietin gene (TPO) or its receptor c-MPL. TPO mutations described so far lead to thrombopoietin overproduction through increased translation of m-RNA. Unilateral transverse reduction limb defects are usually sporadic and generally thought to be caused by vascular disruptions. Reports of inherited unilateral limb defects are extremely rare. In the present study, we describe a family with segregation of G185T TPO mutation in the 5′ UTR region in 4 subjects with thrombocythemia. Three of these patients also present congenital transverse limb defects. Association of these events gives a strong hint of the in vivo involvement of thrombopoietin in vasculogenesis, confirming the role of TPO in human development of the hemangioblast, the embryonic progenitor of the hematopoietic and endothelial lineages. This is the first report showing that vascular disruptions could be secondary to specific gene derangements.

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Shedding light on an old mystery: Thalidomide suppresses survival pathways to induce limb defects

Cell Cycle ◽

10.4161/cc.7.9.5793 ◽

2008 ◽

Vol 7 (9) ◽

pp. 1121-1127 ◽

Cited By ~ 69

Author(s):

Jürgen Knobloch ◽

Ulrich Rüther

Keyword(s):

Limb Defects ◽

Survival Pathways

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Lethal neonatal bone marrow failure syndrome with multiple congenital abnormalities, including limb defects, due to a constitutional deletion of 3′ MECOM

Haematologica ◽

10.3324/haematol.2017.185033 ◽

2018 ◽

Vol 103 (4) ◽

pp. e173-e176 ◽

Cited By ~ 2

Author(s):

Lars T. van der Veken ◽

Merel C. Maiburg ◽

Floris Groenendaal ◽

Mariëlle E. van Gijn ◽

Andries C. Bloem ◽

...

Keyword(s):

Bone Marrow ◽

Congenital Abnormalities ◽

Bone Marrow Failure ◽

Bone Marrow Failure Syndrome ◽

Limb Defects ◽

Multiple Congenital Abnormalities

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Postmortem Diagnosis of Heart-hand Syndrome Associated With a 7p22.1p22.3 Deletion in a 16-week-old Fetus

Pediatric and Developmental Pathology ◽

10.1177/1093526618799293 ◽

2018 ◽

Vol 22 (2) ◽

pp. 146-151

Author(s):

Aude Tessier ◽

Patrick Callier ◽

Nathalie LeMeur ◽

Thierry Frebourg ◽

Jean-Christophe Sabourin ◽

...

Keyword(s):

Growth Retardation ◽

Great Artery ◽

Human Case ◽

Pelvic Kidney ◽

Cardiac Malformation ◽

Male Fetus ◽

Postmortem Diagnosis ◽

Limb Defects ◽

The Third ◽

Limb Anomalies

We report a male fetus with a 6.8 Mb deletion on chromosome 7p22.1p22.3 at 16 weeks of gestation. The fetus presented a heart-hand syndrome with great artery malposition, bilateral radial ray deficiency, a single pelvic kidney, and growth retardation. This deletion involves a minimal deleted region for cardiac malformation and the RAC1 gene, previously described in limb anomalies in mice. This fetus is the third human case with limb defects and RAC1 deletion.

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Punctate Calcification Group

Bone Dysplasias ◽

10.1093/med/9780190626655.003.0010 ◽

2018 ◽

pp. 351-378

Author(s):

Jürgen W. Spranger ◽

Paula W. Brill ◽

Christine Hall ◽

Gen Nishimura ◽

Andrea Superti-Furga ◽

...

Keyword(s):

Autosomal Dominant ◽

Clinical Findings ◽

Differential Diagnoses ◽

Chondrodysplasia Punctata ◽

Limb Defects ◽

Dominant Type ◽

Radiographic Features ◽

Keutel Syndrome ◽

Punctate Calcification ◽

Autosomal Dominant Type

This chapter discusses punctate calcification group and related disorders and includes discussion on Greenberg dysplasia, chondrodysplasia punctata Conradi-Hünermann type, CHILD (congenital hemidysplasia with ichthyosiform erythroderma and limb defects) syndrome, chondrodysplasia punctata (rhizomelic type), chondrodysplasia punctata (brachytelephalangic type), chondrodysplasia punctata (autosomal dominant type), chondrodysplasia punctata (tibia-metacarpal type), and Keutel syndrome. Each discussion includes major radiographic features, major clinical findings, genetics, major differential diagnoses, and a bibliography.

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