Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings

Abstract

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/ abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases. K E Y W O R D S digital fibroma, filamin A, hypopigmented patch, smooth muscle hamartoma, TODPD

Terminal osseous dysplasia with pigmentary defects in a Chinese girl with the FLNA mutation: A case report and published work review

“…5 These conditions suggested that FLNA may modulate the activity of transforming growth factor-b, which in turn regulates the expression of elastin. 3 However, Azakli et al 10 reported that a biopsy obtained from an alopecic area of a scalp revealed elastic fibers within the dermis that were of normal shape and number. Similarly, in our case, Verhoeff-Van Gieson staining of the two biopsies from the atrophic macule on the forehead and digital fibroma both revealed normal elastic fibers in the dermis.…”

Interaction of LARP4 to filamin A mechanosensing domain regulates cell migrations

“…FLNA is a F-actin cross-linking protein and acts as a scaffold for a wide range of molecules, including intracellular signaling molecules, adhesion molecules, ion channels and transcription factors ( Stossel et al, 2001 ; Popowicz et al, 2006 ; Zhou et al, 2007 ; Nakamura et al, 2011 ). FLNA mutations related to various human diseases including peri-ventricular nodular heterotopia, familial cardiac valvular dystrophy, skeletal dysplasias and thrombocytopenia ( Nurden et al, 2011 ; Clapham et al, 2012 ; van der Werf et al, 2013 ; Fernández et al, 2018 ; Azakli et al, 2019 ; Toomer et al, 2019 ).…”