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Nail-patella syndrome
SYNDROME
Nail-patella syndrome
the LMX1B gene which is located on the distal end of the long arm of chromosome 9 in the region 9q34.6 It is thought to occur in 1 in 50,000 newborns.7 The severity and incidence of each feature of nail patella syndrome is unpredictable and can vary within the same family. The mutation in the LMX1B gene is in the majority inherited, however spontaneous mutations can occur.
Charlotte Jones Donna Diamond Rouin Amirfeyz Martin Gargan
Clinical features Nail dysplasia This is the commonest abnormality in nail-patella syndrome and is seen in 98% of patients. Nails may be missing completely, hypoplastic, ridged, pitted or separated into two by a skin ridge. The thumbnails are most affected and the severity tends to decrease towards the little finger. The ulnar border of the thumb is more involved than the radial. Finger nails are more commonly affected than the toenails and the changes are often symmetrical. Changes are usually present at birth. Triangular lunula are also seen and are sometimes the only abnormality of the nail.8
Abstract Nail patella is one of the familial syndromes commonly asked on the FRCS (Trauma & Orth) exam. This article reviews the latest scientific information available and high-lights the key features.
Keywords iliac horn; Nail-patella syndrome; radial head dislocation; patella dyslasia
Introduction Patella hypoplasia The patellae in patients with NPS are small, irregularly shaped or completely absent.9 When present the patella is unstable, often causing the presenting complaint of NPS to be recurrent lateral dislocation. This is exacerbated by hypoplasia of the lateral femoral condyle. A septum which runs from the patella to the intercondylar groove divides the knee into two compartments. Due to the lateral femoral condyle hypoplasia, genu valgum (knock knees) occurs, although infrequently genu varum is also seen.9 Knee pain is the main complaint of patients with NPS in the longer term.10
Nail-patella syndrome (NPS), also know as hereditary onychoosteodysplasia, displays a quartet of main findings: nail dysplasia patella hypoplasia elbow dysplasia iliac horns. Other features seen in this syndrome include renal problems, ophthalmological problems and other orthopaedic manifestations. The earliest description of nail dysplasia associated with skeletal dysplasia dates back to 1820 when Chatelain described a patient with congenital anomalies of the nails, elbows and knees.1 In 1897, Little quoted the description by Sedgewick suggesting the hereditary nature of the disorder in the description of a family with 18 members, from four generations, having absent thumbnails and patellae.2 The presence of iliac horns was first noted by Fong in 1946 during routine urography. Fong saw conical bony projections on the dorsolateral aspects of the ilia, which he termed ‘‘iliac horns’’3 or ‘‘Fong’s horns’’. These were not associated with the syndrome until a few years later by Mino et al. 1948 and Thompson et al. 1949 (Figure 1).4,5
Elbow dysplasia Straightening the elbow may be difficult and there is a varying cubital valgus. The elbow joint is characteristically dysplastic with hypoplasia of the lateral side of the elbow joint, involving the radial head, capitellum and lateral humeral condyle. Abnormal articulation of radial head and capitellum often results in a dislocated radial head.9,11 Pterygia (webbing) may occur across the elbow joint (Figure 2).
Genetics Nail patella syndrome is a genetic disorder that is transferred via autosomal dominant inheritance. It is caused by a mutation in
Charlotte Jones Medical Student, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK. Donna Diamond DCR(R) BSc PgC Superintendent Paediatric Radiographer, Bristol Royal Hospital for Children, Bristol, UK. Rouin Amirfeyz FRCS (Trauma & Orth) MSc MD Specialist Registrar in Trauma and Orthopaedics, Bristol Royal Infirmary, Bristol, UK. Martin Gargan FRCS (Trauma & Orth) MA Consultant Paediatric Orthopaedic Surgeon, Bristol Royal Hospital for Children, Bristol, UK.
ORTHOPAEDICS AND TRAUMA 23:5
Figure 1 Radiograph of adult pelvis showing centrally placed iliac horns.
362
Ó 2009 Elsevier Ltd. All rights reserved.
SYNDROME
population. Once a diagnosis of NPS is established regular screening for glaucoma should be implemented.
Orthopaedic treatments Treatment of NPS is mainly supportive and, since a significant number of people with NPS are asymptomatic, surgical treatment is not necessary. In a review of 44 patients with NPS only 20 received surgical intervention for knee contractures or a mal-aligned patella. The best results were obtained using a combination of full posterior capsular release for flexion contractures and quadricepsplasty for flexion contracture along with proximal and distal patellar realignment.9 A case report of a patient with NPS having an established congenital dislocation of the patella describes successful treatment using the Stanisavljevic procedure.21 Arthroscopic management often proves difficult due to the presence of an intraarticular septum. Asymptomatic dislocation of the radial head is common in younger children with symptoms occasionally becoming apparent later on in life. Surgical excision of the radial head does little to improve range of movement, however does provide symptomatic relief. Excision in the premature skeleton does not appear to be associated with significant problems, despite the procedure traditionally being carried out post skeletal maturity.9 Poor results following the treatment of anticubital pterygium with a 90 fixed flexion deformity were reported in 1998 by Song et al. Poor function and recurrence of deformity occurred following a soft tissue release with Ilizarov external fixation and distraction.22 Iliac horns are largely impalpable, asymptomatic and require no treatment. Foot deformities are frequently the primary complaint in children with NPS. These are treated using the standard methods, but can often be more resistant to successful treatment.9,23 A
Figure 2 Radiograph showing hypoplastic elbow with radial head dislocation.
Iliac horns Iliac horns are pathognomonic of NPS and present in over 80% of patients.9e12 They arise bilaterally at the site of attachment of the gluteus medius muscles and project posterolaterally.13 They may be palpable. Other orthopaedic manifestations Frequently described features of NPS that do not contribute to the diagnosis include: Shoulder girdle dysplasia14 Short stature15 Talipes equinovarus (club feet)8 Calcaneo-valgus feet8,15 Dislocation of the hips15 Madelung’s deformity16 Large joint contractures Generalised joint hyperextensibility is a common feature, particularly of the fingers.
REFERENCES 1 Chatelain (1820), quoted by Roeckherath W. The Nail-patella syndrome. Fortschr Geb Rontgenstr 1951; 75: 700e4. 2 Little EM. Congenital absence or delayed development of the patella. Lancet 1897; 2: 781e4. 3 Fong EE. ‘‘Iliac horns’’ (symmetrical bilateral central posterior iliac processes). Radiology 1946; 47: 517e8. 4 Mino RA, Mino VH, Livingstone RG. Osseous dysplasia and dystrophy of the nails. Review of the literature and report of a case. Am J Roentgenol 1948; 60: 633e41. 5 Thompson EA, Walker ET, Weens HS. Iliac horns. An osseous manifestation of hereditary arthrodysplasia associated with dystrophy of the fingernails. Radiology 1949; 53: 88e92. 6 Sato U, Kitanaka S, Sekine T, Takahashi S, Ashida A, Igarashi T. Functional characterization of LMX1B mutations associated with nailpatella syndrome. J Pediatr Res 2005; 57: 783e8. 7 Wynne-Davies R, Hall C, Apley AG. Atlas of skeletal dyplasias. Edinburgh: Churchill-Livingstone; 1985. p. 614. 8 Beals R, Eckhardt AL. Hereditary onycho-osteodysplasia (Nail-patella syndrome): a report of nine kindreds. J Bone Joint Surg Am 1969; 51: 505e16. 9 Guidera KJ, Satterwhite Y, Ogden JA, et al. Nail-patella syndrome: a review of 44 orthopaedic patients. J Pediatr Orthop 1991; 11: 737e42.
Kidney involvement The most important non-orthopaedic condition in NPS is nephropathy, which is reported to be present in more than 60% of cases.17 The course of the nephropathy is variable between patients, with around 30% of cases resulting in end-stage renal failure.18 Renal biopsy is diagnostic. Immediate referral to nephrology is essential following diagnosis of NPS. Ophthalmological findings Another non-orthopaedic manifestation of NPS is open-angle glaucoma.19,20 Lester’s sign, a clover-leaf shaped area of darker pigmentation on the inner margins of the iris, is also seen at a higher prevalence in patients with NPS than in the general
ORTHOPAEDICS AND TRAUMA 23:5
363
Ó 2009 Elsevier Ltd. All rights reserved.
SYNDROME
10 Beguiristain JL, de Rada PD, Barriga A. Nail-patella syndrome long term evolution. J Pediatr Orthop B 2003; 12(1): 13e16. 11 Yakish SD, Fu FH. Long-term follow-up of the treatment of a family with nail-patella syndrome. J Pediatr Orthop 1983; 3: 360e3. 12 Goshen E, Schwartz A, Zilha LR, Zwas ST. Bilateral accessory iliac horns: pathognomonic findings in nail-patella syndrome. Scintigraphic evidence on bone scan. Clin Nucl Med 2000; 25: 476e7. 13 Lazzeri S, Nori G, Matocci GP, Di Filippo P. Hereditary osteo-onychodysplasia of nail-patella syndrome: description of one case and literature review. J Orthop Trauma 2005; 6: 105e9. 14 Loomer RL. Shoulder girdle dysplasia associated with nail-patella syndrome. A case report and literature review. Clin Orthop Relat Res 1989; 238: 112e6. 15 Maini PS, Mittal RL. Hereditary onycho-osto-arthrodysplasia. J Bone Joint Surg Am 1966; 48: 924e30. 16 Duthie RB, Hecht F. The inheritance and development of the nailpatella syndrome. J Bone Joint Surg Br 1963; 45B: 259e67. 17 Knoers NVAM, Bongers EMHF, Van Beersum SEC, Lommen EJP, Van Bokhoven H, Hol FA. Nail-patella syndrome: identification of
ORTHOPAEDICS AND TRAUMA 23:5
18 19
20
21
22 23
364
mutations in the LMx1B gene in Dutch families. J Am Soc Nephrol 2000; 11: 1762e6. Meyrier S, Rizzo R, Gubier MC. The nail-patella syndrome. A review. J Nephrol 1990; 2: 100e40. Farley FA, Lichter PA, Downs CA, McIntosh I, Vollrath D, Richards J. An orthopaedic scoring system for nail-patella syndrome and application to a kindred with variable expressivity and glaucoma. J Pediatr Orthop 1999; 19: 624e31. Lichter PR, Richards JF, Downs CA, Stringham HM, Boehnke M, Farley FA. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol 1997; 124: 506e15. Marumo K, Fujii K, Tanaka T, Takeuchi H, Saito H, Koyano Y. Surgical management of congenital permanent dislocation of the patella in nail patella syndrome by Stanisavljevic procedure. J Orthop Sci 1999; 4: 446e9. Song HR, Cho SH, Koo KH, Jung ST, Shin HS. Treatment of antecubital pterygium in the nail-patella syndrome. J Pediatr Orthop 1998; 7B: 27e31. Hogh J, Macnicol MF. Foot deformities associated with onychoosteodysplasia. A familial study and review of associated features. Int Orthop 1985; 9: 135e8.
Ó 2009 Elsevier Ltd. All rights reserved.
Nail-patella syndrome
the LMX1B gene which is located on the distal end of the long arm of chromosome 9 in the region 9q34.6 It is thought to occur in 1 in 50,000 newborns.7 The severity and incidence of each feature of nail patella syndrome is unpredictable and can vary within the same family. The mutation in the LMX1B gene is in the majority inherited, however spontaneous mutations can occur.
Charlotte Jones Donna Diamond Rouin Amirfeyz Martin Gargan
Clinical features Nail dysplasia This is the commonest abnormality in nail-patella syndrome and is seen in 98% of patients. Nails may be missing completely, hypoplastic, ridged, pitted or separated into two by a skin ridge. The thumbnails are most affected and the severity tends to decrease towards the little finger. The ulnar border of the thumb is more involved than the radial. Finger nails are more commonly affected than the toenails and the changes are often symmetrical. Changes are usually present at birth. Triangular lunula are also seen and are sometimes the only abnormality of the nail.8
Abstract Nail patella is one of the familial syndromes commonly asked on the FRCS (Trauma & Orth) exam. This article reviews the latest scientific information available and high-lights the key features.
Keywords iliac horn; Nail-patella syndrome; radial head dislocation; patella dyslasia
Introduction Patella hypoplasia The patellae in patients with NPS are small, irregularly shaped or completely absent.9 When present the patella is unstable, often causing the presenting complaint of NPS to be recurrent lateral dislocation. This is exacerbated by hypoplasia of the lateral femoral condyle. A septum which runs from the patella to the intercondylar groove divides the knee into two compartments. Due to the lateral femoral condyle hypoplasia, genu valgum (knock knees) occurs, although infrequently genu varum is also seen.9 Knee pain is the main complaint of patients with NPS in the longer term.10
Nail-patella syndrome (NPS), also know as hereditary onychoosteodysplasia, displays a quartet of main findings: nail dysplasia patella hypoplasia elbow dysplasia iliac horns. Other features seen in this syndrome include renal problems, ophthalmological problems and other orthopaedic manifestations. The earliest description of nail dysplasia associated with skeletal dysplasia dates back to 1820 when Chatelain described a patient with congenital anomalies of the nails, elbows and knees.1 In 1897, Little quoted the description by Sedgewick suggesting the hereditary nature of the disorder in the description of a family with 18 members, from four generations, having absent thumbnails and patellae.2 The presence of iliac horns was first noted by Fong in 1946 during routine urography. Fong saw conical bony projections on the dorsolateral aspects of the ilia, which he termed ‘‘iliac horns’’3 or ‘‘Fong’s horns’’. These were not associated with the syndrome until a few years later by Mino et al. 1948 and Thompson et al. 1949 (Figure 1).4,5
Elbow dysplasia Straightening the elbow may be difficult and there is a varying cubital valgus. The elbow joint is characteristically dysplastic with hypoplasia of the lateral side of the elbow joint, involving the radial head, capitellum and lateral humeral condyle. Abnormal articulation of radial head and capitellum often results in a dislocated radial head.9,11 Pterygia (webbing) may occur across the elbow joint (Figure 2).
Genetics Nail patella syndrome is a genetic disorder that is transferred via autosomal dominant inheritance. It is caused by a mutation in
Charlotte Jones Medical Student, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK. Donna Diamond DCR(R) BSc PgC Superintendent Paediatric Radiographer, Bristol Royal Hospital for Children, Bristol, UK. Rouin Amirfeyz FRCS (Trauma & Orth) MSc MD Specialist Registrar in Trauma and Orthopaedics, Bristol Royal Infirmary, Bristol, UK. Martin Gargan FRCS (Trauma & Orth) MA Consultant Paediatric Orthopaedic Surgeon, Bristol Royal Hospital for Children, Bristol, UK.
ORTHOPAEDICS AND TRAUMA 23:5
Figure 1 Radiograph of adult pelvis showing centrally placed iliac horns.
362
Ó 2009 Elsevier Ltd. All rights reserved.
SYNDROME
population. Once a diagnosis of NPS is established regular screening for glaucoma should be implemented.
Orthopaedic treatments Treatment of NPS is mainly supportive and, since a significant number of people with NPS are asymptomatic, surgical treatment is not necessary. In a review of 44 patients with NPS only 20 received surgical intervention for knee contractures or a mal-aligned patella. The best results were obtained using a combination of full posterior capsular release for flexion contractures and quadricepsplasty for flexion contracture along with proximal and distal patellar realignment.9 A case report of a patient with NPS having an established congenital dislocation of the patella describes successful treatment using the Stanisavljevic procedure.21 Arthroscopic management often proves difficult due to the presence of an intraarticular septum. Asymptomatic dislocation of the radial head is common in younger children with symptoms occasionally becoming apparent later on in life. Surgical excision of the radial head does little to improve range of movement, however does provide symptomatic relief. Excision in the premature skeleton does not appear to be associated with significant problems, despite the procedure traditionally being carried out post skeletal maturity.9 Poor results following the treatment of anticubital pterygium with a 90 fixed flexion deformity were reported in 1998 by Song et al. Poor function and recurrence of deformity occurred following a soft tissue release with Ilizarov external fixation and distraction.22 Iliac horns are largely impalpable, asymptomatic and require no treatment. Foot deformities are frequently the primary complaint in children with NPS. These are treated using the standard methods, but can often be more resistant to successful treatment.9,23 A
Figure 2 Radiograph showing hypoplastic elbow with radial head dislocation.
Iliac horns Iliac horns are pathognomonic of NPS and present in over 80% of patients.9e12 They arise bilaterally at the site of attachment of the gluteus medius muscles and project posterolaterally.13 They may be palpable. Other orthopaedic manifestations Frequently described features of NPS that do not contribute to the diagnosis include: Shoulder girdle dysplasia14 Short stature15 Talipes equinovarus (club feet)8 Calcaneo-valgus feet8,15 Dislocation of the hips15 Madelung’s deformity16 Large joint contractures Generalised joint hyperextensibility is a common feature, particularly of the fingers.
REFERENCES 1 Chatelain (1820), quoted by Roeckherath W. The Nail-patella syndrome. Fortschr Geb Rontgenstr 1951; 75: 700e4. 2 Little EM. Congenital absence or delayed development of the patella. Lancet 1897; 2: 781e4. 3 Fong EE. ‘‘Iliac horns’’ (symmetrical bilateral central posterior iliac processes). Radiology 1946; 47: 517e8. 4 Mino RA, Mino VH, Livingstone RG. Osseous dysplasia and dystrophy of the nails. Review of the literature and report of a case. Am J Roentgenol 1948; 60: 633e41. 5 Thompson EA, Walker ET, Weens HS. Iliac horns. An osseous manifestation of hereditary arthrodysplasia associated with dystrophy of the fingernails. Radiology 1949; 53: 88e92. 6 Sato U, Kitanaka S, Sekine T, Takahashi S, Ashida A, Igarashi T. Functional characterization of LMX1B mutations associated with nailpatella syndrome. J Pediatr Res 2005; 57: 783e8. 7 Wynne-Davies R, Hall C, Apley AG. Atlas of skeletal dyplasias. Edinburgh: Churchill-Livingstone; 1985. p. 614. 8 Beals R, Eckhardt AL. Hereditary onycho-osteodysplasia (Nail-patella syndrome): a report of nine kindreds. J Bone Joint Surg Am 1969; 51: 505e16. 9 Guidera KJ, Satterwhite Y, Ogden JA, et al. Nail-patella syndrome: a review of 44 orthopaedic patients. J Pediatr Orthop 1991; 11: 737e42.
Kidney involvement The most important non-orthopaedic condition in NPS is nephropathy, which is reported to be present in more than 60% of cases.17 The course of the nephropathy is variable between patients, with around 30% of cases resulting in end-stage renal failure.18 Renal biopsy is diagnostic. Immediate referral to nephrology is essential following diagnosis of NPS. Ophthalmological findings Another non-orthopaedic manifestation of NPS is open-angle glaucoma.19,20 Lester’s sign, a clover-leaf shaped area of darker pigmentation on the inner margins of the iris, is also seen at a higher prevalence in patients with NPS than in the general
ORTHOPAEDICS AND TRAUMA 23:5
363
Ó 2009 Elsevier Ltd. All rights reserved.
SYNDROME
10 Beguiristain JL, de Rada PD, Barriga A. Nail-patella syndrome long term evolution. J Pediatr Orthop B 2003; 12(1): 13e16. 11 Yakish SD, Fu FH. Long-term follow-up of the treatment of a family with nail-patella syndrome. J Pediatr Orthop 1983; 3: 360e3. 12 Goshen E, Schwartz A, Zilha LR, Zwas ST. Bilateral accessory iliac horns: pathognomonic findings in nail-patella syndrome. Scintigraphic evidence on bone scan. Clin Nucl Med 2000; 25: 476e7. 13 Lazzeri S, Nori G, Matocci GP, Di Filippo P. Hereditary osteo-onychodysplasia of nail-patella syndrome: description of one case and literature review. J Orthop Trauma 2005; 6: 105e9. 14 Loomer RL. Shoulder girdle dysplasia associated with nail-patella syndrome. A case report and literature review. Clin Orthop Relat Res 1989; 238: 112e6. 15 Maini PS, Mittal RL. Hereditary onycho-osto-arthrodysplasia. J Bone Joint Surg Am 1966; 48: 924e30. 16 Duthie RB, Hecht F. The inheritance and development of the nailpatella syndrome. J Bone Joint Surg Br 1963; 45B: 259e67. 17 Knoers NVAM, Bongers EMHF, Van Beersum SEC, Lommen EJP, Van Bokhoven H, Hol FA. Nail-patella syndrome: identification of
ORTHOPAEDICS AND TRAUMA 23:5
18 19
20
21
22 23
364
mutations in the LMx1B gene in Dutch families. J Am Soc Nephrol 2000; 11: 1762e6. Meyrier S, Rizzo R, Gubier MC. The nail-patella syndrome. A review. J Nephrol 1990; 2: 100e40. Farley FA, Lichter PA, Downs CA, McIntosh I, Vollrath D, Richards J. An orthopaedic scoring system for nail-patella syndrome and application to a kindred with variable expressivity and glaucoma. J Pediatr Orthop 1999; 19: 624e31. Lichter PR, Richards JF, Downs CA, Stringham HM, Boehnke M, Farley FA. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol 1997; 124: 506e15. Marumo K, Fujii K, Tanaka T, Takeuchi H, Saito H, Koyano Y. Surgical management of congenital permanent dislocation of the patella in nail patella syndrome by Stanisavljevic procedure. J Orthop Sci 1999; 4: 446e9. Song HR, Cho SH, Koo KH, Jung ST, Shin HS. Treatment of antecubital pterygium in the nail-patella syndrome. J Pediatr Orthop 1998; 7B: 27e31. Hogh J, Macnicol MF. Foot deformities associated with onychoosteodysplasia. A familial study and review of associated features. Int Orthop 1985; 9: 135e8.
Ó 2009 Elsevier Ltd. All rights reserved.