Juvenile macular dystrophy and forearm pronation‐supination restriction presenting with features of distal arthrogryposis type 5

Abstract

The distal arthrogryposes are a heterogeneous group of conditions characterized by congenital contractures of hands and feet, and autosomal dominant inheritance. The concurrence of ophthalmoplegia and additional ocular findings distinguish distal arthrogryposis type 5 (DA5). This rare subtype has been described in 33 patients to date and its clinical spectrum of physical findings is still poorly understood. We report on a family with three individuals with DA5. The index case came to our attention because of restricted forearm pronation-supination and juvenile macular dystrophy. Further examination revealed short stature, firm muscles, stiff spine with lumbar hyperlordosis, generalized mild limitation of the large joints, external rotation of the hips, unilateral ptosis, exophoria, and abnormal photopic and scotopic responses on electroretinogram testing. However, there was no overt evidence of contractures of the distal joints. Examination of other affected family members revealed restricted range of movement of the small joints together with ulnar deviation of the fingers, and clarified the diagnosis. Our observations suggest that DA5 may have a very mild musculoskeletal phenotype and it should be considered in the differential of congenital contracture syndromes even in the absence of obvious distal joint involvement. Our observations also suggest that fundoscopy and ocular electrophysiological studies might be helpful in the evaluation of patients with otherwise unclassified distal arthrogryposes.

A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation

“…The unique feature in the present family was shortening of the 1st and 5th toes (all patients) and metatarsal/metacarpal synostosis (Patient III‐1). The abnormal patterning of the feet and hands may be regarded as a rare syndromic component of PIEZO2 ‐associated DA5 because vertebral and phalangeal fusions were previously reported in DA5 [Krieger and Espiritu, ; Sach, ; Kawira and Bender, ; Zeiter and Boniuk, ; Castori et al, ]. Excavation of the optic nerve head (Patient Ⅱ‐6) further expanded a phenotypic diversity of ocular changes in the disorder.…”

“…In addition, it is known that DA5 is associated with other ocular abnormalities, including corneal leukoma, derangement of corneal collagen, retinal pigmentation, and macular and choroidal folds [Scharander‐Stumpel et al, ; Beals and Weleber, ; Sahni et al, ]. A small subset of DA5 is known to show vertebral and phalangeal fusions [Krieger and Espiritu, ; Sach et al, 1978; Kawira and Bender, ; Zeiter and Boniuk, ; Castori et al, ]. Restrictive lung disease resulting in fatal pulmonary hypertension has recently attracted attention in certain families of DA5 [Pallotta et al, ; Beals and Weleber, ; Williams et al, ; Castori et al, ].…”

“…A small subset of DA5 is known to show vertebral and phalangeal fusions [Krieger and Espiritu, ; Sach et al, 1978; Kawira and Bender, ; Zeiter and Boniuk, ; Castori et al, ]. Restrictive lung disease resulting in fatal pulmonary hypertension has recently attracted attention in certain families of DA5 [Pallotta et al, ; Beals and Weleber, ; Williams et al, ; Castori et al, ].…”

Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis

“…Currently, DAs are subdivided into 10 types, depending on the number and nature of additional features (2,4). Of these, DA Type 5 (DA5) [online Mendelian inheritance in man (OMIM) 108145] has been described in the literature for more than 70 y and can be further divided into several subtypes based on additional phenotypic features (1,2,(4)(5)(6)(7)(8)(9). DA5 itself is an autosomal dominant multisystem disorder characterized by multiple distal contractures, characteristic facies, ophthalmoplegia with ptosis, (2), and in some cases restrictive lung disease with pulmonary hypertension (4,9).…”