Pediatr Nephrol (1995) 9:354-356 Pediatric Nephrology Brief report A case of craniomandibular dermatodysostosis associated with focal glomerulosclerosis Eugenia Pedagogos 1, Grant Flanaga#, David M. A. Francis 2, Gavin J. BeckerI, David M. Danks 3, Rowan G. Walker 1 Departments of 1Nephrology and 2 Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia, 3 Murdoch Institute, Royal Children's Hospital, Melbourne, Victoria, 3050, Australia Received July 5, 1994; received in revised form and accepted December 28, 1994 Abstract. This paper reports an isolated case of the ex- ceedingly rare cutaneo-skeletal condition craniomandibular dermatodysostosis, in which focal glomerular sclerosis and end-stage renal failure developed and renal transplantation was required. Key words: Craniomandibular dermatodysostosis - Focal glomerular sclerosis - Mandibulo acral dysplasia - Renal transplantation Introduction Craniomandibular dermatodysostosis (CMD) is an ex- tremely rare cutaneo-skeletal disorder. There is no known association with renal disease. In our isolated case of this disorder we describe the development of focal glomerular sclerosis, end-stage renal failure and eventual successful renal transplantation. Case report The patient was a son of non-consanguineous Anglo-Saxon parents who presented at the age of 18 months with inability to extend his legs. He was noted to have gross micrognathia, a narrow mouth, a narrow pointed nose set between bulbous cheeks and prominent protuberant eyes (Fig. 1). The skull sutures were all widely open and he had a high and narrow palate. The clavicles were underdeveloped with only a small vestige of bone palpable medially. The chest was narrow and the sternum protuberant. Body proportions were unusual with relatively short limbs, and there was about 15 ° of fixed flexion deformity at the knees. Fingers were broad and short and the nails were dysplastic. The skin over the knees and dorsum of the hands, abdomen and axillae contained atrophic, pigmented patches and the surrounding skin lacked normal pliability and elasticity. By age 7 years his height was 112 cm (3rd percentile). It was evident that his limbs were relatively short and his micrognathia had Correspondence to: E. Pedagogos0 Department of Nephrology, Royal Melbourne Hospital, C/-Post Office RMH 3050, Victoria, Australia led to respiratory obstruction during sleep, so that he was forced to sleep in the upright position. There was an increase in skin change and, although his joint deformities had not changed, he had developed calcified necrotic ulcers on the tips of several of his fingers, ears, elbows and scalp. Biopsies were not performed as local anaesthesia was feared by the child and general anaesthesia had proved to be hazardous when it had been previously attempted for dental extraction. Maxillary and mandibular hypoplasia was evident with a lack of rotation of the incisor teeth. Histology of deciduous teeth showed a reduction in the amount of cementum with complete absence of cellular cementum on the root surface. The clavicles remained hypoplastic and ossification of the pubis and ischium was delayed with failure of formation of the symphysis pubis. Fibroblastic cells cultured from skin showed no metachromasia or other abnormality and no excess mucopolysaccharide was found in the urine [1]. At the age of 18 years difficulties with sleep apnoea necessitated the formation of a tracheostomy. Eighteen months later he was noted to be hypertensive. There was no previous history of renal problems and the family history was unrevealing. Urine microscopy revealed 5,000 glomerular red blood cells/ml and he had nephrotic-range proteinuria (5.5 g/24 h). The creatinine at the time was 0.11 mmol/1 with a urea of 8.2 mmolfl. Other investigations revealed an albumin of 42 g/1 with a total protein of 70 g/1. The serum cholesterol estimation was 6.63 mmolB with a trigly- ceride level of 2.97 mmol/1. Serum complement levels were normal and no anti-nuclear antibody was detected. Intravenous urography and renal arteriography were normal. A percutaneous renal biopsy showed 25 of 35 glomeruli with global cellular sclerosis and many areas of hyalinosis (Fig. 2). Three glomeruli were hypertrophied but otherwise unremarkable. The remaining 7 glomeruli were hypertrophied and showed areas of segmental sclerosis and hyalinosis. No deposits were seen on light microscopy and there were no spikes, crescents or necrotising lesions. There was moderate (predominantly focal) tubular atrophy and a number of atrophic tubules contained protein casts. No crystalline material was seen within the tubules and there was moderately severe interstitial fibrosis which in places had a linear distribution. Arterioles showed muscular hypertrophy and the inter- lobular arteries revealed medial hypertrophy. No amyloid was seen on routine staining for light microscopy. Immunofluorescence revealed segmental mesangial IgM trapping. Electron microscopy was not performed. The appearance was consistent with focal segmental glomerulosclerosis (FGS) or focal and segmental hyalinosis and sclerosis (FSHS) with extensive scarring and tubular atrophy. Four years later he developed hypertensive encephalopathy, cor- tical blindness and grand mal seizures; all of which resolved with adequate blood pressure control. Over the next 18 months his renal function deteriorated (serum creatinine increased from 0.10 to