Table 1.
Clinical Features of Individuals with Homozygous Mutations in MESD
| Findings | Individual 1 | Individual 2 | Individual 3 | Individual 4 | Individual 5 |
|---|---|---|---|---|---|
| mutation in MESD (homozygous) | c.632dupA p.Lys212Glufs∗19 |
c.631_632del p.Lys211Glufs∗19 |
c.676C>T p.Arg226∗ |
c.632dupA p.Lys212Glufs∗19 |
c.607_611del p.Thr203Alafs∗26 |
| country of origin | Brazil | Turkey | Portugal | Brazil | Brazil |
| gender | female | male | male | male | male |
| consanguinity | yes | yes | yes | yes | yes |
| age at first visit (years) | after birth | 3 years, 4 months | 4 years, 6 months | 10 years | 6 months |
| age at last visit (years) | 1 year, 5 months (death) | 8 years, 4 months | 11 years, 1 months | 12 years, 2 months | 7 months (death) |
| age at start of bisphosphonate treatment | 15 days | 3 years, 5 months | 3 years, 6 months | 5 years | not treated |
| age at end of bisphosphonate treatment | NA | NA | approx. 11 years | regular use since 2015 not treated from 2012–2014 |
not treated |
| birth weight and birth length | W = 2,135 g (−2.35 SD), L = 45 cm (−1.93 SD) (39 WG) |
W = 1,550 g (−2.8 SD) L = 43 cm (−2.58 SD) (34 WG) |
W = 3,730 g (+0.38 SD) L = 51 cm (+0.38 SD) (37 WG) |
W = 2,730 g (−1.35 SD) L = 52 cm (+0.76 SD) (term) |
W = 2,465 g (−1.73 SD) L = 42 cm (−2.94 SD) (37 WG) |
| confirmed prenatal fractures | yes | no | no | no | yes |
| age at first fracture (months) | prenatal | 11 months | 24 months | 24 months | prenatal |
| color of sclera | bluish | white | white | white | bluish |
| eye abnormalities | NFA | no | no | no | no |
| dentinogenesis imperfecta | no | no | no | no | NA |
| disorganized dentition/clinical oligodontia | NA | yes | yes | yes | NA |
| radiographic evidence of oligodontia | NA | NA | NA | yes | NA |
| hypermobility of joints | no | no | NA | no | no |
| cardiac impairments | patent foramen ovale with a small left to right shunt | NA | NA | NA | no |
| hearing impairment | no | slight conductive hearing loss due to adenoid hyperplasia | no | NA | NA |
| old fractures of extremities | yes | yes (five fractures) | yes (right clavicle 2 years left femur 3 years 6 months right femur 4 years) |
yes | yes (fractures of both humeri, ribs, femur, and clavicle) |
| vertebral/thoracic cage fractures | no | yes (multiple fractures of vertebrae, ribs, and both scapulae) | vertebral compression fractures | yes (vertebrae and ribs) | difficult to assess (multiple fractures of ribs). |
| retarded gross motor function | yes | yes | yes | yes | yes |
L = length; NA = not available; NFA = not formally assessed; SD = standard deviation; WG = weeks of gestation; W = weight