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333 GLASGOW VARIANT OF THANATOPHORIC DYSPLASIA: EXPANDING THE PHENOTYPE.
  1. A. Kwan,
  2. H. E. Hoyme
  1. Stanford University School of Medicine, Stanford, CA

Abstract

Thanatophoric dysplasia (TD) is a lethal short-limbed skeletal dysplasia with characteristic findings of micromelia, bowed femurs, narrow thorax, and short ribs. The Glasgow variant of TD has overlapping radiographic and histopathologic findings and is also considered to be lethal in the neonatal period. We report on a patient with radiographic findings consistent with the Glasgow variant of TD who survived beyond infancy and who has features of an ectodermal dysplasia. Our proband was born at 37 weeks' gestation with birth weight at the 10th%ile, length < 3rd %ile and OFC at the 50th%ile. Polyhydramnios and decreased limb length were noted prenatally, and amniocentesis was normal. Postnatal evaluations revealed rhizomelic shortening of the limbs and a small chest circumference. Skeletal radiographs were interpreted as consistent with the Glasgow variant of TD. Pulmonary hypoplasia, anemia, VSD and bicuspid aortic valve, strabismus, bilateral inguinal hernias, and hypospadias were present. A head MRI revealed third and lateral ventricle dilatation, small foramen magnum, and low cerebellar tonsils. Ectodermal abnormalities included fine, scant scalp hair, minimal body hair, delayed dental eruption, thin, brittle fingernails, and hypoplastic toenails. Speech and gross and fine motor skills were initially delayed, but at 8 years of age, are age appropriate. Sequencing of the FGFR3 gene has been normal, and molecular studies are ongoing to further characterize the etiology of this condition. The Glasgow variant of TD was originally described in two female siblings with micromelia, curved femurs, mild platyspondyly, shortened ribs, and abnormal endochondral ossification, features also seen in TD. Also present were hypoplasia of the ilia, pubic and ischial bones, cataracts, anemia, and hepatomegaly, which were not previously reported in TD. One child died at 26 hours and the other was terminated at 22 weeks' gestation. Chromosome analysis was performed on one child and was normal. Inheritance was presumed to be autosomal recessive. Our proband has skeletal features consistent with the Glasgow variant of TD, but longevity and ectodermal findings distinguish him from previously reported cases. We further expand the phenotype of the Glasgow variant of TD to include survival beyond infancy and ectodermal components and suggest that these factors be considered when counseling families about outcomes for patients with radiograph findings suggestive of TD.

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