Acta Dermato-Venereologica 99-7CompleteContent | Page 23

SHORT COMMUNICATION 695 Mutation in FAM111B Causes Hereditary Fibrosing Poikiloderma with Tendon Contracture, Myopathy and Pulmonary Fibrosis Fuying CHEN, Luyao ZHENG, Yue LI, Huaguo LI, Zhirong YAO* and Ming LI* Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. *E-mail: [email protected], [email protected] Accepted Apr 2, 2019; E-published Apr 2, 2019 Congenital poikiloderma is a dermatological condition characterized in the first few months of life by epidermal atrophy, telangiectasias, and variegated pigmentation (hypo- and hyperpigmentation). Poikiloderma often pre- sents a diagnostic challenge in the first few months of life, with differential diagnoses such as Rothmund-Thomson syndrome (RTS), the eponymous Weary form of hereditary sclerosing poikiloderma, Clericuzio-type poikiloderma with neutropaenia, and Kindler syndrome (1–3). A distinct autosomal dominant form of hereditary fibrosing poikiloderma (HFP) was first described in a South African family in 2006 (3). HFP with tendon con­ tractures, myopathy, and pulmonary fibrosis (abbreviated POIKTMP) is caused by mutations in FAM111B (Homo sapiens family with sequence similarity 111, member B), encoding a trypsin-like cysteine/serine peptidase (4, 5). FAM111B has also been implicated in susceptibility to pro- state cancer (6). The main clinicopathological features of POIKTMP comprise early-onset poikiloderma, especially on the face and sun-exposed areas, alopecia, hypohidrosis with heat intolerance, growth retardation, multiple muscle contractures, in particular triceps surae muscle contractu- res, progressive muscle weakness, progressive pulmonary fibrosis, exocrine pancreatic dysfunction, liver impairment, cataracts and haematological abnormalities (4, 7–9). This study, which was approved by the ethics commit- tees of Shanghai Jiaotong University School of Medicine and conducted in accordance with the principles of the Declaration of Helsinki, describes the clinical and genetic background of a POIKTMP patient with FAM111B mis- sense mutation. CASE REPORT We describe here a new case of POIKTMP in a 5-month-old Chi- nese boy. He was born of non-consanguineous Chinese parents, and had no similar illness history or familial history of atopy. He was the product of a full-term, uncomplicated pregnancy and de- livery, with a birth-weight of 3.5 kg, with no immediate perinatal abnormalities. After 6 days, however, erythema, with desquamation on the cheeks with a recurrent papulovesicular facial eruption was noted. Thereafter the clinical features comprised progressive generalized poikiloderma, telangiectasia, xerosis and innumerable hypo- and hyperpigmentary macules, measuring between 3 and 6 mm, predominantly on the face and in other sun-exposed areas; and worsening non-scarring alopecia affecting the scalp, eyebrows and eyelashes (Fig. 1a–d). The patient also had eczematous lesions on the legs and feet. No lymphoedema of the upper and/or lower extremities was observed. A biopsy from the leg revealed conspicuous thickening of the spinous layer, blister formation under the epidermis, cellulose- like substance deposition and inflammatory cell infiltration in the blister with scattered eosinophils and neutrophils. In allergen detection, the patient was allergy to worm. Other normal or negative findings included: weight and height within normal limit; full blood count; immunoglobulins; comple- ment; anti-ds-DNA antibodies, anti-ANA antibodies, anti-CENPB antibodies; TPPA, RPR, anti-TP antibodies; no heat intolerance; no respiratory abnormalities; no liver impairment, no exocrine pancreatic insufficiency; no muscle weakness or wasting; no ten- don abnormalities or joint contractures; no nail abnormalities; no cataracts; no recurrent gingivitis; no palmoplantar keratoderma. Following informed consent, the genomic DNA of the proband was analysed using a gene probe consisting of 541 genetic loci of genodermatoses. This revealed a heterozygous missense mutation, c.A1873C in FAM111B, which results in the mutation p.Thr625Pro (Fig. 2a). No mutation was detected in his non-consanguineous parents (Fig. 2b, c). This mutation converts Thr625 to Pro and was not detected in his healthy parents or in 100 unrelated healthy Chinese individuals (200 alleles) by Sanger sequencing (10). The mutation was also absent from the public database (NCBI, dbSNP135, the 1000 Genomes Project, and HapMap8) and our internal datasets, suggesting that this was most likely the deleterious mutation in this patient. In summary, we Fig. 1. Clinical features of hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) in a 5-month-old Chinese boy. (a–d) Aged 5 months, he exhibited generalized poikiloderma, and alopecia with a resolving papulovesicular eruption; eczema-like dermatosis was also present. (e) Haematoxylin and eosin (H&E)-stained sections of proband skin. Scale bar: 200 µm. Written permission to publish these photos are given. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3186 Acta Derm Venereol 2019; 99: 695–696