posted 11-26-2003 02:47 PM            

The proband had growth retardation, with a peak stature of 40 in. (101.6 cm), and a weight of 100 lb. (45.36 kg). He possessed a distinct facial phenotype, including craniosynostosis, severe nasal maxillary hypoplasia, telechanthus, prominent superorbital ridge, and depressed nasal bridge. The proband’s father and brother had the same skeletal syndrome (father’s peak stature was 48 in. (121.92 cm)). All affected members also manifested with shortened neck, broad and shortened thumbs, and brachydactyly. In addition, the proband and his father never had tooth eruption, as documented by radiographs, however it is unclear as to whether the proband’s brother had tooth eruption. The proband underwent tibial osteotemies to correct lower extremity bowing, but was active most of his life. Physical activity declined over his lifespan because of severe pain in the knees, hips, and back, and he developed pathologic fractures involving the proximal humerus bilaterally. The proband’s father also had limited activity later in life and had insufficiency fractures in both feet.

Laboratory values for the proband at age 26, and his father at age 55 were available. The proband and his father had marked hypophosphatemia with serum phosphorus concentrations of 0.9 to 1.0 mg/dl (normal 2.7-4.5 mg/dl), whereas total serum calcium was normal. In addition, they had inappropriately normal (and on two occasions frankly low) 1,25(OH)2 vitamin D3 concentrations. Their tubular maximum phosphate transport/glomerular filtration rate (TmP/GFR) was markedly low indicating severe renal phosphate wasting. Alkaline phosphatase was elevated, however intact PTH and nephrogenous cAMP were normal.