Fig. 1.

Proband's evolution of the phenotype, his pedigree and family history, and genetic data. A. Photograph of the proband at the age of 4–5 years, documenting that pectus excavatum, flexion of elbows and knees were already manifested. He used to wear a female swimming suit to cover pectus excavatum. B, C. Long thin face, high forehead, hooked nose, short clavicles, severe angled kyphosis, bony outgrowths at the elbows, absence of subcutaneous fat and reduction of muscle mass represent the current phenotype. D. Detail of the proband's face showing prominent orbital arches, iris depigmentation and coarse hair. E–G. Proband's radiographs of the left elbow, forearm and column, showing: (E–G) diffuse severe osteoporosis; (E, F) the exostoses at the head of ulna and radius and its dislocation; (F) metaphyseal flaring and dyaphiseal wavy contours of long bones; (G) wedge-shaped D11 vertebrae, representing the fulcrum of his severe-angled kyphosis, and L1 vertebrae. H. Filled symbol and symbols filled in lighter color represent, respectively, the proband and his two possibly more mildly affected male relatives (see the details in the clinical report). Female carriers of the pathogenic variant are shown with a dot inside the symbol; asterisk, members genotyped in the study; [m.i.], pathogenic variant inferred; y, years. I. From top to bottom: electropherograms of the ATP7A gene sequence of wild type (III-3), carriers (II-1, III-1, and IV-2), and the proband (III-2); schematic view of ATP7A cDNA and protein structure showing in red the approximative position of the pathogenic variant (modified from [24]). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)