Osteopetrosis, progressive sensorineural deafness, glaucoma, alopecia and cardiomyopathy in a 13 year old female: New syndrome or mild variant of YunisVaron syndrome?

Abstract

This youngster presented at 10 years of age with bilateral genu valgum and rapidly progressive sensorineural hearing loss. Prior history was significant for delayed motor milestones in early childhood, but normal cognitive development. Family history was non-contributory. Initial exam was remarkable for bilateral proptosis and exotropia that was reported to be of recent onset associated with increased intraocular pressures. Mild alopecia was noted on the scalp. Hypodontia was noted with mostly primary teeth present. Cutaneous exam revealed taut, shiny skin on the fingers and diffuse cutis marmorata. Fingers were slightly tapered and there was bilateral genu valgum with a lumbering gait and muscle wasting of the calves. Radiographic studies revealed diffuse osteosclerosis suggestive of a form of osteopetrosis and the patient subsequently went on to have a number of pathologic fractures. A biopsy of the iliac crest revealed increased osteoblastic activity. Multiple CT and MRJ studies failed to find any evidence of optic or acoustic nerve compression despite progression to complete deafness, but calcification of the basal ganglia was noted incidentally. Two surgeries for glaucoma resulted in stabilization of intraocular pressures although the proptosis progressed. Studies for metabolic bone disease were normal including: alkaline phosphatase, calcium, phosphorus and 25 OH-vitamin D. Carbonic anhydrase I and II deficiencies were ruled out and a collagen vascular work-up was also normal. At twelve years of age the patient presented for care because of progressive shortness of breath and was found to have a severe, dilated cardiomyopathy. Primary and secondary carnitine deficiencies were ruled out and she stabilized on digoxin and lasix. Although this may represent a unique clinical entity, there are some overlapping features with Yunis-Varon syndrome(YVS), an autosomal recessive condition that generally presents in infancy. Overlapping features include: alopecia, hypodontia, bony sclerosis with pathological fractures as well as one child with YVS reported with dilated cardiomyopathy. However, the prenatal growth retardation, clavicular abnormalities, micrognathia and hand defects that are common in YVS are not seen in this patient. Other considerations include an unrecognized mitochondrial disorder or variant of osteopetrosis. A muscle biopsy will be done in the near future to provide additional diagnostic information.