Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the
clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of
the disorder including short staure (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel
with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8),
dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of
8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motoradaptive
language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium
and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short stature
is a chracteristic feature of pycnodysostosis. Seven of the 8 children were born short (length standard deviation score
[SDS] 5 23 to 21.5) . Deceleration of linear growth was significant during the first 3 years of life. All the children had height
SDS below –3 at the end of their third year of life. Although short stature is a feature of this genetic disorder, defective growth
hormone (GH) secretion in response to provocation with clonidine and glucagon was found in 4 of the 8 patients. These 4
patients had pituitary hypoplasia on the magnetic resonance imaging (MRI) of their brain. In addition, 3 of these 4 patients
had demyelination of the cerebrum. Patients with pycnodysostosis (n 5 8) had low circulating concentrations of insulin-like
growth factor-1 (IGF-1) compared with normal age-matched short children with constitutional short stature (CSS). IGF-I
increased significantly after injecting GH for 3 days in these patients. Physiologic replacement with GH (18 U/m2/week)
divided in daily evening doses subcutaneousely increased IGF-1 concentration and improved linear growth velocity and
height standard deviation scores (HtSDS) in the 4 children with GH deficiency. These data ruled out GH resistance and proved
the usefulness of GH therapy in the management of short stature in these patients. In summary, some patients with
pycnodysostosis have partial GH deficiency and low IGF-1 concentration. GH therapy markedly increases IGF-I secretion and
improves their linear growth. MRI study of the brain including the hypothalamic-pituitary area is recommended in these
children because of the high incidence of pituitary hypoplasia and cerebral demyelination.
Copyright © 2001 by W.B. Saunders Company |
