Epidermal Nevus Syndrome (ENS), also known as Cutaneous Skeletal
Hypophosphatemia Syndrome or
Linear Sebaceous Nevus Syndrome, is caused by a mosaic somatic mutation of RAS (Rat
Sarcoma genes) which leads to abnormally elevated levels of
fibroblast growth factor 23 (FGF23). FGF23 is a major regulator in
phosphate homeostasis. There are multiple disorders, along with
Epidermal Nevus Syndrome (ENS), that result in unusually high circulating levels of FGF23. This increase ultimately leads to renal
phosphate wasting and reduced levels of 1,25-dihydroxy
vitamin D. Across these disorders, the clinical symptoms are similar and often include
osteomalacia (
hypophosphatemic rickets in children),
muscle weakness,
fatigue, joint
deformities, bone
pain, and fractures.
Burosumab (
KRN23), is an
IgG1 monoclonal antibody that binds to the FGF23 receptor and inhibits the activity of FGF23. This leads to an increase in serum
phosphate levels.
Burosumab emerged as a potential
therapy in FGF23 overactivity disorders.
Burosumab was successful in the treatment of
X-linked hypophosphatemia (XLH) and is now FDA-approved for its treatment. Studies have indicated that
Burosumab therapy in subjects with XLH consistently increases and sustains serum
phosphorus levels and tubular reabsorption of
phosphate without a major impact on urine
calcium levels or
vitamin D metabolism. We studied the effect of
Burosumab treatment in a single pediatric patient with
Epidermal Nevus Syndrome. Serum
phosphorus rose gradually as we titrated the dose of
Burosumab upwards. During treatment, a persistent elevation of
parathyroid hormone levels was noted along with a persistent elevation of serum
calcium. We presumed the patient had tertiary
hyperparathyroidism. However, after the removal of three parathyroid glands, the pathology came back with a single enlarged
parathyroid adenoma. Subsequently, his
calcium and PTH, and
phosphorus levels stabilized while taking only
Burosumab. ClinicalTrials.gov NCT04320316.