Rita Barone á Piero Pavone Rosario R. Tri®letti á Enrico Parano Tuberous breast deformity in an adolescent girl with Hurler-Scheie syndrome Received: 9 May 2000 /Accepted: 5 July 2000 Comment This work was carried out in the Division of Paediatric Neurology, Department of Paediatrics, University of Catania, Italy in collaboration with the Division of Pediatric Neurology, De- partment of Neuroscience, Cornell University, New York, USA We present a female patient with Hurler-Scheie syndrome who also had tuberous breast deformity. This may be related to the underlying defect in connective tissue catabolism in this disorder. The mucopolysaccharidoses MPS) are inherited disorders of glycosaminoglycan catabolism. They are chronic, multisystemic diseases mainly aecting the skeleton, eyes and internal organs [4]. Tuberous breast deformity TBD) is a rare malformation present- ing at the age of mammary development [5]. We report an adolescent female patient with Hurler/Scheie syndrome MPS type I H/S) and TBD and we discuss possible mechanisms underlying this unusual association. The patient, the third child born to consanguineous parents, was ®rst admitted to our unit at the age 7 years. Her weight was 19.5 kg 3rd percentile) and height 107.5 cm  3rd percentile). Mild facial coarsening and macroglossia were evident. Head circumference was 51 cm 50th percentile). Skeletal changes included a short trunk with slight dorsal kyphoscoliosis and pectus carinatum; the abdomen was prominent with a small umbilical hernia and moderate visceral enlargement. Cognitive function was normal; deep tendon re¯exes were slightly increased. The diagnosis of MPS type I was established by demonstration of a-iduronidase de®ciency in cultured ®broblasts. We continued to follow her as an outpatient. Pubertal develop- ment was normal but menarche was somewhat delayed at 15 years. Abnormalbreastdevelopmentgraduallybecameevident,prompting further evaluation. At this time age 16 years) pertinent clinical ®ndings included bone changes with disproportionate dwar®sm height 133 cm:  3rd percentile), lumbar gibbus and ¯exion contracturesoftheelbowsandkneesFig. 1).Facialappearancewas mildlycoarseandcornealcloudingwasnotedwhilehearingfunction was unimpaired. Bilateral mammary deformity was evident with de®cientandcontractedbaseandimpressiveexpansionofthenipple- areolar complex and glandular herniation through the areola suggesting a diagnosis of TBD Fig. 1). Basal FSH and LH, serum prolactin and oestradiol were normal. Surgical correction of the breast deformity was proposed but this was refused by the patient. TBD has been estimated to occur in 5/10000 of the healthy population; little is known on the pathogenesis of this condition whichcanbeeectivelytreatedbyplasticandreconstructivesurgery [5]. MPS type I is due to a-iduronidase de®ciency leading to the storage and massive urinary excretion of dermatan sulphate and heparan sulphate; it may be distinguished into three dierent subtypesbasedonageatonsetandseverityoftheclinicalsymptoms. Early onset mental retardation occurs in Hurler disease whereas cognitive functions are normal in the mild variant or Scheie syndrome [4]. The patient here reported has the intermediate phenotype known as Hurler/Scheie syndrome with severe skeletal involvementbutnormalcognitivefunction[4].Theassociationofan enzyme disorder aecting connective tissue with TBD has not been reportedbeforeandmaybefortuitous.However,aseachconditionis rare, the occurrence of both MPS and tuberous breast syndrome in the same subject makes it unlikely to be a chance association. Thereiscompellingevidencethatalterationsinconnectivetissue accumulation and structure may play a functional role in the development of hernias [2]; inguinal and umbilical hernias are recurrent clinical features of MPS patients [1, 4], particularly MPS types I, II, VI and VII. Recently it has been demonstrated that Fig. 1A, B Pro®le of patient demonstrating A) inguinal hernia and scoliosis and B) bilateral mammary deformity with expansion of nipple areolar complex and narrow breast base characteristic of TBD 936