Newly recognized syndrome of metaphyseal undermodeling, spondylar dysplasia, and overgrowth: report of two adolescents and a child

Gen Nishimura; Tomonobu Hasegawa; Eiichi Kinoshita; Yoko Tanaka; Kenzi Kurosawa; Masaaki Yoshimoto

doi:10.1002/ajmg.a.30030

Newly recognized syndrome of metaphyseal undermodeling, spondylar dysplasia, and overgrowth: report of two adolescents and a child

Am J Med Genet A. 2004 Jul 15;128A(2):204-8. doi: 10.1002/ajmg.a.30030.

Authors

Gen Nishimura¹, Tomonobu Hasegawa, Eiichi Kinoshita, Yoko Tanaka, Kenzi Kurosawa, Masaaki Yoshimoto

Affiliation

¹ Japanese Skeletal Dysplasia Consortium, Tokyo, Japan.

PMID: 15214018
DOI: 10.1002/ajmg.a.30030

Abstract

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Body Height
Bone Diseases, Developmental / diagnosis
Bone Diseases, Developmental / diagnostic imaging
Bone Diseases, Developmental / genetics*
Estrogens / metabolism
Female
Glypicans
Growth Hormone / metabolism
Heparan Sulfate Proteoglycans / genetics
Humans
Infant, Newborn
Insulin-Like Growth Factor I / metabolism
Insulin-Like Growth Factor II / genetics
Male
Osteochondrodysplasias / diagnosis*
Osteochondrodysplasias / diagnostic imaging
Osteochondrodysplasias / genetics
Protein-Tyrosine Kinases / genetics
Puberty, Delayed / genetics
Radiography
Receptor, Fibroblast Growth Factor, Type 3
Receptors, Fibroblast Growth Factor / genetics
Syndrome
Time Factors

Substances

Estrogens
Glypicans
Heparan Sulfate Proteoglycans
Receptors, Fibroblast Growth Factor
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Growth Hormone
FGFR3 protein, human
Protein-Tyrosine Kinases
Receptor, Fibroblast Growth Factor, Type 3