| Abstract|| |
Ectodermal dysplasia (ED) is a group of disorders involving developmental defects of the ectodermal structures, with abnormalities in the skin, hair, nails and sweat glands. Ankyloblepharon - ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is characterized by eyelid fusion, ED and cleft lip/palate. We report a 15-year-old Omani boy with AEC syndrome who presented with end-stage renal disease (ESRD) requiring renal replacement therapy. Genitourinary anomalies including hypospadiasis, posterior urethral stricture and bilateral vesicoureteric reflux were noted. These led to secondary focal segmental glomerulosclerosis and ESRD. Screening for genitourinary anomalies and renal function tests must be performed in all patients with ED to facilitate early detection of renal disease and appropriate management.
|How to cite this article:|
Mohan D, Sugathan DK, Railey M, Alrukhaimi M. Renal failure in Hay-Wells syndrome. Saudi J Kidney Dis Transpl 2013;24:1214-6
| Introduction|| |
Ectodermal dysplasia (ED) is a relatively rare skin disorder with a prevalence of 7/10,000 live births. Ankyloblepharon - ectodermal defects-cleft lip/palate (AEC) syndrome is one of the 150 known ED syndromes. To the best of our knowledge, the association of renal anomalies and renal failure with AEC syndrome has not been previously reported and hence this case report.
| Case Report|| |
A 15-year-old Omani boy, born to non-consanguinous parents, was referred to our institution from a Primary Health Center with hematuria of four months' duration. He was detected to have hypertension with severe renal impairment (S. creatinine was 11.7 mg/dL, urea was 299 mg/dL, K was 4.4 mmol/L, HCO 3 was 13.4 mmol/L). Renal ultrasound revealed bilateral small kidneys (right kidney: 6.6 cm × 3 cm, left kidney: 5.6 cm × 2.6 cm). Urine analysis revealed 3+ proteinuria with 30 - 35 red blood cells and a sterile culture. Urine protein/creatinine ratio was 15.75. He was diagnosed to have chronic kidney disease (CKD) stage 5, secondary to chronic glomerulonephritis.
We noted him to have dysmorphic features - frontal bossing, absent hair and eyelashes, narrow palpebral fissures and abnormal dentition. He also had dystrophic nails and hyperpigmented dry skin and there was a history of anhidrosis. His intelligence was subnormal and there had been developmental delay. The absence of hair and eyelashes, dystrophy of nails and history of anhidrosis suggested ED [Figure 1].
|Figure 1: AEC syndrome: Note the absence of eyebrows and eyelashes, absent skull hair (which is masked by a cap) and eyes that are narrow after surgical repair of ankyloblepharon. Cleft lip and palate were surgically corrected in his childhood (permission obtained for use of photograph from patient's mother).|
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On further questioning and review of his past medical history, it was found that he had fusion of eyelids on both sides (ankyloblepharon), which were surgically corrected in infancy. He also had cleft palate and lip at birth, which were corrected in early childhood. A Pubmed search revealed these features to be suggestive of ankyloblepharon, ectodermal defects and clefting syndrome (AEC syndrome). All other family members were healthy. Genetic testing could not be carried out due to non-availability.
At the age of 3 years, he was also detected to have unequal sized kidneys (right kidney: 6.61 cm × 3.5 cm, left kidney: 4.6 cm × 2.4 cm). A DMSA scan revealed a small cortical scar in the right kidney and shrunken left kidney. Serum creatinine was 0.7 mg/dL at that time.
He was lost to follow-up for nine years till the age of 12 years, when the serum creatinine was recorded to be 1.2-1.9 mg/dL at a Primary Health Center. A formal nephrology consult was never sought as he had been on irregular follow-up. The last recorded serum creatinine prior to presentation to us was 1.9 mg/dL at the age of 13 years (estimated GFR by Schwartz formula: 29 mL/min).
At the time of presentation in January 2010, he had features of CKD stage 5 with massive proteinuria. Lower urinary tract symptoms prompted a urology consultation. CT KUB revealed a distended large capacity bladder with mildly diffuse thickened wall. A cystourethrogram showed a long segment of posterior urethral stricture with bilateral vesicoureteric reflux. Foley's catheterization was technically difficult, necessitating a suprapubic catheter placement. However, renal functions failed to improve significantly despite relief of obstruction, suggesting established end-stage renal disease (ESRD). In view of massive proteinuria, secondary focal segmental glomerulosclerosis (FSGS) is likely to have been concomitantly present. Renal biopsy was not attempted in view of bilaterally shrunken kidneys.
He was commenced on maintenance hemodialysis through a permanent right internal jugular hemodialysis catheter.
| Discussion|| |
AEC syndrome is characterized by ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), ectodermal defects (sparse wiry hair; skin erosions and unique pigmentary changes; nail changes; dental changes; subjective decrease in sweating capacity) and cleft lip/ palate.  It is also known as Hay-Wells syndrome after the physicians who first described the condition in 1976.  In addition, developmental delay, syndactyly, recurrent otitis media and hearing loss have also been described. The diagnosis of AEC syndrome is based on clinical findings and molecular genetic testing of TP63, a homologue of the p53 tumor suppressor gene, the only gene known to be associated with AEC syndrome. 
AEC syndrome is inherited in an autosomal dominant manner. Approximately 30% of individuals have an affected parent and approximately 70% have a de novo mutation.  In our patient, the mutation was most likely de novo as all other family members were healthy.
Renal anomalies have been previously reported to be associated with some of the ED syndromes. , These include the EEC syndrome (ED, ectrodactyly and clefting syndrome) and the ED, cleft lip/palate with acral anomalies syndrome. Ectopia vesicae, ureteric reflux with hydroureteronephrosis and renal defects such as ectopic, fused or horseshoe-shaped kidneys have been associated with these syndromes. We performed a detailed Pubmed search and could not find any previous reports of genitourinary defects or renal failure with ED of the Hay-Wells type. This could well be the first report in the literature of such an association.
Although our patient was detected to have reflux nephropathy with unequal sized kidneys and cortical scarring at the age of three years, he was lost to regular follow-up and presented to us at 15 years of age with ESRD and massive proteinuria. Presence of posterior urethral stricture, bilateral vesicoureteric reflux and obstructive uropathy were detected. Massive proteinuria suggested the development of secondary FSGS associated with reflux nephropathy.
We present this case to highlight the rare association of genitourinary anomalies and end-stage renal failure with AEC syndrome, which by itself is rare. The onset and progress of renal failure could have been delayed had he been on regular follow-up. Screening for genitourinary anomalies and renal function tests must be performed in all patients with ED to facilitate early detection of renal disease and appropriate management.
| References|| |
|1.||Sutton VR, Bree AF, Van Bokhoven H. In: Pagon RA, ed. Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993. Available from: http://www. ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene &part=aec [Last cited on 2010 June 08]. |
|2.||Hay RJ, Wells RS. The syndrome of ankyloblepharon, ectodermal defects, and cleft lip and palate: An autosomal dominant condition. Br J Dermatol 1976;94:277-89. |
|3.||Fete M, vanBokhoven H, Clements SE, et al. International research symposium on Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome. Am J Med Genet 2009; 149A:1885-93. |
|4.||Richieri-Costa A, Guion-Almeida ML, Freire-Maia N, Pinheiro M. Autosomal recessive cleft lip/palate, ectodermal dysplasia, and minor acral anomalies: Report of a Brazilian family. Am J Med Genet 1992;44:158-62. |
|5.||Wallis CE. Ectrodactyly (split hand/split foot) and ectodermal dysplasia with normal lip and palate in four generation kindred. Clin Genet 1988;34:252-7. |
Specialist Registrar, Department of Nephrology, Dubai Hospital, Dubai
United Arab Emirates