Newly recognized syndrome of metaphyseal undermodeling, spondylar dysplasia, and overgrowth: report of two adolescents and a child.
We report on a previously undescribed syndrome characterized by generalized skeletal alterations and overgrowth in three unrelated individuals: a boy who died at age 16 years, a 16-year-old girl, and a 15-month-old boy. The skeletal changes included bony overgrowth of the skull base, spondylar dysplasia, and undermodeling of the tubular bones. Bone age was accelerated in early childhood. Overgrowth, which was independent of GH-IGF axis, was of prenatal onset in the two boys, but postnatal in the girl. In the two adolescents, growth rate did not decline with age, and high-dose estrogen therapy failed to induce physeal fusion. Their adolescent height reached +4 approximately +7 SD of the mean. Delayed puberty in the girl and cryptorchidism and hypospadias in the younger boy raised the possibility that hypogonadism is a syndromic constituent. Molecular analysis of IGF2, GPC3, and FGFR3 in the older boy yielded no abnormalities.
Nishimura
Gen
G
Japanese Skeletal Dysplasia Consortium, Tokyo, Japan.
Hasegawa
Tomonobu
T
Kinoshita
Eiichi
E
Tanaka
Yoko
Y
Kurosawa
Kenzi
K
Yoshimoto
Masaaki
M
D000293:Adolescent; D001827:Body Height; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D053673:Glypicans; D013006:Growth Hormone / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011628:Puberty, Delayed / Q000235:genetics; D011859:Radiography; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013577:Syndrome; D013997:Time Factors
D004967:Estrogens; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3