Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant syndrome?

Abstract

Members of two generations of a South African family have a unique syndrome comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis. The condition is clinically important as the skin changes, which involve the face, have considerable cosmetic impact, while lung involvement is potentially lethal in adulthood. Skin manifestations which facilitate diagnosis include facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal atrophy. The scalp, facial and body hair are fine and scanty. The tendon contractures lead to progressive digital flexion deformities and abnormalities of the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as progressive dyspnoea. Pedigree data are compatible with an autosomal dominant mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic and fibrous bands and not tendon contractures and is not associated with potentially lethal pulmonary fibrosis. Rather than name this disorder a variant of Weary syndrome, it might be prudent to use as an umbrella title one composed by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis described as inconsistently associated with Weary syndrome) and HSP with tendon/pulmonary involvement (current family) may be classified. The manifestations in this family differ from other poikilodermata and, to the best of our knowledge, have not been previously documented.

Expanding phenotype of hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis caused by FAM111B mutations: Report of an additional family raising the question of cancer predisposition and a short review of early-onset poikiloderma

“…This family's phenotype, characterized by poikiloderma, hypohidrosis, small feet and hands with tendon contractures or atrophy of the thenar and hypothenar eminences, was reminiscent of the case of a South African family reported in 2006 1 and recently found to have a mutation in the FAM111B gene 5 . Sanger sequencing of the family reported herein identified also a mutation in FAM111B : p.[Ser628Arg]; [=] c.[1884T>A] (Fig 3) that segregated with the disease confirming that the diagnosis belonged to the POIKTMP spectrum.…”

“…This genetic disorder was first identified in a South African family in 2006 1 . To date, 3 families and 9 independent sporadic cases have been reported 2, 3, 4.…”

CUGC for hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)

“…Its mode of inheritance and its main clinical features were inferred from observations made in a twogeneration multiplex South African family, 1 the study of which contributed to the identification of causative variants in FAM111B. 2 Three FAM111B (NM_198947.3) missense variants, c.1861T4G (p.(Tyr621Asp)), c.1879A4G (p.Arg627Gly), and c.1883G4A (p.(Ser628Asn)), and one in-frame deletion, c.1262_1264delAAG (p.(Lys421del)), have been reported so far in individuals with POIKTMP.…”

The rise of developmental genetics – a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative

“…The technology is cost effective, uncomplicated and is able to permanently and selectively edit DNA. [12] The CRISPR/Cas9 system is modelled on a viral defence system of microorganisms in which a pair of small RNA 'molecule scissors' , as it were, are designed to a specific target site on double-stranded DNA. The RNA molecule is complementary to the DNA target and can be devised to find a binding site on any gene of interest.…”