Multiple supernumerary molars, anterior openbite, and large ear lobules in mucopolysaccharidosis type VI patient

Smith

Casal

et al. 2019

Mucopolysaccharidosis Type VII (MPS7, also called β-glucuronidase deficiency or Sly syndrome; MIM 253220) is an extremely rare autosomal recessive lysosomal storage disease, caused by mutations in the GUSB gene. β-glucuronidase (GUSB) is a lysosomal hydrolase involved in the stepwise degradation of glucuronic acid-containing glycosaminoglycans (GAGs). Patients affected with MPS VII are not able to completely degrade glucuronic acid-containing GAGs, including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and heparan sulfate. The accumulation of these GAGs in lysosomes of various tissues leads to cellular and organ dysfunctions. Characteristic features of MPS VII include short stature, macrocephaly, hirsutism, coarse facies, hearing loss, cloudy cornea, short neck, valvular cardiac defects, hepatosplenomegaly, and dysostosis multiplex. Oral manifestations in patients affected with MPS VII have never been reported. Oral manifestations observed in three patients consist of wide root canal spaces, taurodontism, hyperplastic dental folli-cles, malposition of unerupted permanent molars, and failure of tooth eruption with malformed roots. The unusual skeletal features of the patients include maxillary hypoplasia, hypoplastic midface, long mandibular length, mandibular prognathism, hypoplastic and aplastic mandibular condyles, absence of the dens of the second cervical vertebra, and erosion of the cortex of the lower border of mandibles. Dogs affected with MPS VII had anterior and posterior open bite, maxillary hypoplasia, premolar crowding, and mandibular prognathism. Unlike patients with MPS VII, the dogs had

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 68%

Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII

Smith

Casal

et al. 2019

“…Also, in the α‐galactosidase A deficient ( Aga −/− ) mouse model of Fabry disease, the teeth showed no gross morphological abnormalities, and ST were not noted [Goldberg et al, ]. This seems to be pathogenetically distinct from other conditions with ST, and we found only two other associations with storage disorders, both single occurrences: mucopolysaccharidosis type VI [Kayserili and Kantaputra, ], and fucosidosis [Macpherson, ]. We conclude that these co‐occurrences are coincidental.…”

Section: Exclusions Of Commonly Cited Syndromesmentioning

confidence: 49%

“…Disorders were excluded if only a single affected patient had been reported. Commonly cited examples of this include fucosidosis [Macpherson, ], incontinentiapigmenti [Himelhoch et al, ], Marfan syndrome [Mallineni et al, ], mucopolysaccharidosis type VI [Kayserili and Kantaputra, ], and enamel‐renal‐gingival syndrome [Kantaputra et al, ].…”

Section: Introductionmentioning

confidence: 99%

Syndromes with supernumerary teeth

Lubinsky

2016

Self Cite

While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein–Taybi syndrome; Nance–Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg–Pakistani syndrome (craniosynostosis and dental anomalies), and insulin‐resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann–Streiff syndrome, Fabry disease, Ehlers–Danlos syndrome, Apert and Crouzon syndromes, Zimmermann–Laband syndrome, and Ellis–van Creveld syndrome. © 2016 Wiley Periodicals, Inc.

“…The frequency of the clinical features was compared with that of previously reported cohort by Azevedo et al [] (Table ). The clinical and oral manifestations of patient 17 has already been reported in detail [Kayserili and Kantaputra, ]. The study of oral manifestations of patients 1–16 has been reported [Kantaputra et al, ].…”

Section: Resultsmentioning

confidence: 99%

Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations

Kayserili

Güven

et al. 2014

Self Cite

Mucopolysaccharidosis (MPS) type VI or Maroteaux-Lamy syndrome is a very rare autosomal recessive lysosomal storage disease, caused by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB). Clinical examination, biochemical studies, and molecular genetic analyses have been performed in 17 patients affected with MPS VI from 15 unrelated families from Thailand, India, and Turkey. Large ear lobule appears to be a newly recognized finding of this syndrome. Mutation analysis of the ARSB gene revealed seven missense and three frameshift mutations of which eight were novel. Novel missense mutations were p.Asp53Asn, p.Val376Glu, p.Glu390Lys, p.Pro445Leu, and p.Trp450Cys, while an Indian patient was homozygous for two novel missense mutations (p.Pro445Leu and p.Trp450Cys). Three novel frameshift mutations were p.Pro70fsX123, p.Ser403fs, and p.Thr526fs. Two previously reported mutations, p.Arg160Gln and p.Leu321Pro, were also observed in our cohort. The amino acid Arg160 appears to be the mutational hot spot for the ARSB gene. Five patients homozygous for p.Leu321Pro mutation had early onset of the disease, and haplotype analysis showed that the mutation is a founder mutation in Turkish population.