PMC3362267_01
Genealogical tree of the propositus. Genealogical tree showing that the mother of the index case was born of the marriage of her parents, who were relatives of the 5th generation, descended from the paternal line of her great, great grandfathers who were brothers. In addition, the father of the propositus also descends from the same family as his wife, but through the sister of one of the great, great grandfathers who were brothers. It is for this reason that we included the relatives of 6 previous generations in order to demonstrate far consanguinity between the propositus' parents. During questioning, the parents of the propositus stated that none of their relatives showed any alteration in the skin, or at least it was not somewhat rare or notorious that they recall to have listened of their parents or grandfathers. Consanguinity was present in the 5th and 6th generation of this genealogical tree. Pedigree was made using Cyrillic software V.2. (Cyrillic Software, UK).
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F1
The propositus was born at 28 weeks' gestation to a G4 P3 36-year-old mother and a 39-year-old father (consanguineous parents) (fig. 1).
a-d Clinical and X-ray photographs. a Lateral projection of the skull with large, open anterior fontanel. Arrows delimit fontanel amplitude. This X-ray was taken when the patient was 11 months old. b Redundant neck skin. c Swollen eyelids. d Short child, prominent abdomen, protruding umbilicus and redundant skin.
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F2
Intra-oral examination showed a high palate, severe gingival hyperplasia and micrognathia (fig. 2).
a-d Clinical and skeletal X-ray photographs. a Anteroposterior X-ray of the spine, showing anterior failure of fusion of cervical and thoracic vertebrae (arrows) and dysmorphology of lumbosacral vertebral body. b Age 11 months; umbilical hernia. c Lateral X-ray of the spine. d Amplification of c showing small vertebral L1 body with anterior discontinuity by a U-shaped carved indentation.
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F3
A large umbilical hernia was present since birth (5 cm, fig. 3). Skeletal X-rays revealed spinal abnormalities such as: failure of anterior fusion of the cervical and thoracic vertebrae (D1-D8), and a lateral projection revealing a small L1 vertebral body and showing anterior discontinuity with a U-shaped indentation and short phalanges (fig. 3d, fig. 4a, c).
a Light photomicrograph of the skin biopsy showing normal epidermal structure (E) and epithelial dermal elements (arrow). Bundles of collagen fibers appear moderately disorganized in the deep dermal portion (asterisk). HE stain (x40). b Light photomicrograph of the skeletal muscle biopsy where cross- and longitudinal sectioned muscle fibers are observed showing normal structure. No abnormalities are seen except for the wide interfascicular spaces with thin connective tissue fibers (asterisks). HE stain (x40).
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F5
The skin biopsy showed no significant differences in the tissue elements of epidermis and epithelial dermal structures, while moderate disorganization of collagen bundles at the deep dermal portion and subcutaneous connective tissue was observed (fig. 5a). In the muscle biopsy, the muscle fibers in cross- and longitudinal sections appeared normal in structure and thickness, while a wide interfascicular space and thin connective tissue fibers were seen (fig. 5b).