Short case report 125
Rutherfurd syndrome revisited: intellectual disability is not a feature Jenny E. Higgs and Jill Clayton-Smith Clinical Dysmorphology 2015, 24:125–127 Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Manchester, UK
Tel: + 44 161 276 8677; fax: + 44 161 276 6145; e-mail: [email protected] Received 19 December 2014 Accepted 19 January 2015
Correspondence to Jenny E. Higgs, MBBS, PhD, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK
List of key features Noneruption/delayed eruption of teeth Gingival hypertrophy Corneal dystrophy
Clinical summary A 14-year-old boy with a complex family history was seen in the genetic clinic. His father had been diagnosed with Rutherfurd syndrome, a triad of gingival hyperplasia, noneruption of the teeth and corneal dystrophy, some years previously (Fig. 1). Further enquiry revealed that this family were descendents of the original and only family to be described with Rutherfurd syndrome in 1966. The boy’s mother had a confirmed clinical diagnosis of Marfan syndrome. The family pedigree is shown in Fig. 2. On examination the boy has pes planus, hypermobility, high myopia (− 9 D) and is very tall at
202.7 cm (Fig. 3). His aortic root is of normal calibre. He also has classical features of Rutherfurd syndrome with noneruption of his molar teeth, gingival hyperplasia and corneal dystrophy (bilateral corneal vascularization and opacity). The details of his dental phenotype are described in detail in the study by Raja et al. (2008). He had good general health and normal intellectual development. Microarray analysis was normal. Fibrillin testing found a previously undescribed mutation (c.1767T > G, pAsn589Lys) of likely pathogenicity, in an evolutionary conserved amino acid, confirming the diagnosis of Marfan syndrome.
Discussion Rutherfurd syndrome, MIM 18090, also known as oculodental syndrome, was first described by Rutherfurd (1931) and has only been recognized in a single family.
Fig. 1
Father of proband (individual V1). (a) Lower gums, (b) upper gums, (c) corneal appearance of left eye, (d) corneal appearance of right eye.
0962-8827 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/MCD.0000000000000081
126 Clinical Dysmorphology
2015, Vol 24 No 3
Fig. 2
I Rutherfurd syndrome Marfan syndrome II
III
IV LD
LD
V
VI
Family tree. Arrow indicates proband. LD, learning disability.
Fig. 3
Proband (individual VI). (a) Height 202.7 cm, (b) lower gums, (c) upper gums.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Revisiting Rutherfurd syndrome Higgs and Clayton-Smith 127
This report described three generations of a family who had failure of tooth eruption, gingival hypertrophy and visual deficiency. No other abnormalities were reported; in particular hair, nails and sweating were normal. The second account of this condition by Houston and Shotts (1966), described further members of the original family with the same phenotype. In addition two of the family were described as mentally retarded, raising the possibility that learning disability may be part of the condition. However, one of these had no corneal nor teeth abnormalities and therefore was unlikely to have Rutherfurd syndrome. No other members of the family have learning difficulties. Failure of dental eruption may occur as an isolated dominant disorder MIM 125350 due to mutation in PTHR1 (Decker et al., 2008) or as part of other distinctive syndromes including Zimmerman– Laband syndrome (Kim et al., 2007), Ramon syndrome (Ramon et al., 1967) or some types of gingival fibromatosis (Aghili and Goldani Moghadam, 2013). Although ocular findings may be present in both Zimmerman– Laband and Ramon syndrome, these are usually retinal as opposed to cornel changes. Both of these latter syndromes are associated also with intellectual disability.
Rutherfurd syndrome is a distinctive syndrome restricted to dental and corneal phenotypes. Continued follow-up of this family does not support an association of learning difficulties with Rutherfurd syndrome. The genetic basis for the disorder remains to be identified.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Aghili H, Goldani Moghadam M (2013). Hereditary gingival fibromatosis: a review and a report of a rare case. Case Rep Dent 2013:1–4. Decker E, Stellzig-Eisenhauer A, Fiebig BS, Rau C, Kress W, Saar K, et al. (2008). PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet 83:781–786. Houston IB, Shotts N (1966). Rutherfurd’s syndrome: a familial oculo-dental disorder. Acta Paediatr Scand 55:233–238. Kim HG, Higgins AW, Herrick SR, Kishikawa S, Nicholson L, Kutsche K, et al. (2007). Candidate loci for Zimmermann–Laband syndrome at 3p14.3. Am J Med Genet A 143A:107–111. Raja TA, Albadri S, Hood C (2008). Case report: Rutherfurd syndrome associated with Marfan syndrome. Eur Arch Paediatr Dent 9:138–141. Ramon Y, Berman W, Bubis JJ (1967). Gingival fibromatosis combined with cherubism. Oral Surg Oral Med Oral Pathol 24:435–448. Rutherfurd ME (1931). Three generations of inherited dental defect. Br Med J 2:9–11.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Rutherfurd syndrome revisited: intellectual disability is not a feature Jenny E. Higgs and Jill Clayton-Smith Clinical Dysmorphology 2015, 24:125–127 Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Manchester, UK
Tel: + 44 161 276 8677; fax: + 44 161 276 6145; e-mail: [email protected] Received 19 December 2014 Accepted 19 January 2015
Correspondence to Jenny E. Higgs, MBBS, PhD, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Saint Mary’s Hospital, Oxford Road, Manchester M13 9WL, UK
List of key features Noneruption/delayed eruption of teeth Gingival hypertrophy Corneal dystrophy
Clinical summary A 14-year-old boy with a complex family history was seen in the genetic clinic. His father had been diagnosed with Rutherfurd syndrome, a triad of gingival hyperplasia, noneruption of the teeth and corneal dystrophy, some years previously (Fig. 1). Further enquiry revealed that this family were descendents of the original and only family to be described with Rutherfurd syndrome in 1966. The boy’s mother had a confirmed clinical diagnosis of Marfan syndrome. The family pedigree is shown in Fig. 2. On examination the boy has pes planus, hypermobility, high myopia (− 9 D) and is very tall at
202.7 cm (Fig. 3). His aortic root is of normal calibre. He also has classical features of Rutherfurd syndrome with noneruption of his molar teeth, gingival hyperplasia and corneal dystrophy (bilateral corneal vascularization and opacity). The details of his dental phenotype are described in detail in the study by Raja et al. (2008). He had good general health and normal intellectual development. Microarray analysis was normal. Fibrillin testing found a previously undescribed mutation (c.1767T > G, pAsn589Lys) of likely pathogenicity, in an evolutionary conserved amino acid, confirming the diagnosis of Marfan syndrome.
Discussion Rutherfurd syndrome, MIM 18090, also known as oculodental syndrome, was first described by Rutherfurd (1931) and has only been recognized in a single family.
Fig. 1
Father of proband (individual V1). (a) Lower gums, (b) upper gums, (c) corneal appearance of left eye, (d) corneal appearance of right eye.
0962-8827 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/MCD.0000000000000081
126 Clinical Dysmorphology
2015, Vol 24 No 3
Fig. 2
I Rutherfurd syndrome Marfan syndrome II
III
IV LD
LD
V
VI
Family tree. Arrow indicates proband. LD, learning disability.
Fig. 3
Proband (individual VI). (a) Height 202.7 cm, (b) lower gums, (c) upper gums.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Revisiting Rutherfurd syndrome Higgs and Clayton-Smith 127
This report described three generations of a family who had failure of tooth eruption, gingival hypertrophy and visual deficiency. No other abnormalities were reported; in particular hair, nails and sweating were normal. The second account of this condition by Houston and Shotts (1966), described further members of the original family with the same phenotype. In addition two of the family were described as mentally retarded, raising the possibility that learning disability may be part of the condition. However, one of these had no corneal nor teeth abnormalities and therefore was unlikely to have Rutherfurd syndrome. No other members of the family have learning difficulties. Failure of dental eruption may occur as an isolated dominant disorder MIM 125350 due to mutation in PTHR1 (Decker et al., 2008) or as part of other distinctive syndromes including Zimmerman– Laband syndrome (Kim et al., 2007), Ramon syndrome (Ramon et al., 1967) or some types of gingival fibromatosis (Aghili and Goldani Moghadam, 2013). Although ocular findings may be present in both Zimmerman– Laband and Ramon syndrome, these are usually retinal as opposed to cornel changes. Both of these latter syndromes are associated also with intellectual disability.
Rutherfurd syndrome is a distinctive syndrome restricted to dental and corneal phenotypes. Continued follow-up of this family does not support an association of learning difficulties with Rutherfurd syndrome. The genetic basis for the disorder remains to be identified.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Aghili H, Goldani Moghadam M (2013). Hereditary gingival fibromatosis: a review and a report of a rare case. Case Rep Dent 2013:1–4. Decker E, Stellzig-Eisenhauer A, Fiebig BS, Rau C, Kress W, Saar K, et al. (2008). PTHR1 loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet 83:781–786. Houston IB, Shotts N (1966). Rutherfurd’s syndrome: a familial oculo-dental disorder. Acta Paediatr Scand 55:233–238. Kim HG, Higgins AW, Herrick SR, Kishikawa S, Nicholson L, Kutsche K, et al. (2007). Candidate loci for Zimmermann–Laband syndrome at 3p14.3. Am J Med Genet A 143A:107–111. Raja TA, Albadri S, Hood C (2008). Case report: Rutherfurd syndrome associated with Marfan syndrome. Eur Arch Paediatr Dent 9:138–141. Ramon Y, Berman W, Bubis JJ (1967). Gingival fibromatosis combined with cherubism. Oral Surg Oral Med Oral Pathol 24:435–448. Rutherfurd ME (1931). Three generations of inherited dental defect. Br Med J 2:9–11.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
