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Nail–patella syndrome

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Nail–patella syndrome
Other namesNPS
Nail of a patient with nail–patella syndrome
SpecialtyMedical genetics Edit this on Wikidata
Causesmutations in the LMX1B gene.

Nail–patella syndrome is a rare genetic disorder that results in small, poorly developed nails (especially of thumbs) and - next in order/frequency - hypoplastic kneecaps. A unique feature of this syndrome is the usually triangular — rather than semicircular, as in healthy individuals — lunulae at the base of the fingernails[1]. But nail-patella syndrome can also affect many other areas of the body, such as the elbows, chest, hips and others. The name "nail–patella" can be very misleading, because the syndrome usually affects simultaneously many various areas of the body, including even the production of certain proteins.[2] The severity of these effects varies depending on the individual. It is also referred to as iliac horn syndrome, hereditary onychoosteodysplasia (HOOD syndrome), Fong disease or Turner–Kieser syndrome.[3] This syndrome is caused by mutations in the LMX1B gene (see below).

Diagnosis of NPS can be made at birth but is common for it to remain undiagnosed for several generations. While there is no cure available for NPS, treatment is available and recommended.

In the international medical classification (ICD), the syndrome is included in the category Q87.2 - Congenital malformation syndromes predominantly involving limbs.

Signs and symptoms

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The skeletal structures of individuals who have this disorder may have pronounced deformities. As reported by several medical doctors, the following features are commonly found in people who with nail–patella syndrome:[4]

Bones and joints[citation needed]

AP radiograph showing a hypoplastic patella in NPS
AP radiograph of the right iliac crest showing a bony exostosis or posterior iliac horn, which is pathognomonic of NPS
  • Patellar involvement is present in approximately 75 % of patients;[5] however, patellar aplasia occurs in only 20%.
  • In instances in which the patellae are smaller or luxated, the knees may be unstable.
  • The knee joint may appear square.
  • Frequent flat feet and/or other foot deformities.
  • The elbows may have limited motion (e.g., limited pronation, supination, extension).
  • Subluxation of the radial head may occur.
  • Arthrodysplasia of the elbows is reported in approximately 75 % of patients.
  • Exostoses arising from the posterior aspect of the iliac bones ("iliac horns") are present in as many as 75-80% of patients; this finding is considered pathognomonic for the syndrome.
  • Other reported bone changes include scoliosis, scapular hypoplasia, and the presence of cervical ribs.
  • A reduction in bone density, on average by about 8-20 %, which may lead to osteoporosis.[6]
  • General hyperextension of the joints can be present. On the other hand - a possible, sometimes occurring, generalized joint hypermobility/laxity has also been described [7]. However, it is not certain whether the hypermobility results from a mutation of the same gene or a possibly accompanying mutation of some different gene.
  • An elbow of a man with nail–patella syndrome (NPS)
    An elbow of a man with nail–patella syndrome (NPS)
  • This is a view from a different angle of the same man's other elbow
    This is a view from a different angle of the same man's other elbow

Glaucoma is also closely associated with nail-patella, specifically open-angled glaucoma (OAG). Side effects may include frequent headaches, blurred vision, or total vision loss. This occurs gradually over time and symptoms may not be evident in children.[8]

Kidney issues may arise such as deposition of protein in the urine and nephritis. Proteinuria is usually the first sign of kidney involvement. It can reveal itself either rapidly or years after having asymptomatic deposition of protein in the urine, kidney failure occurs in around 15 % of NPS patients (in form of end-stage failure).[9] Irritable bowel syndrome and other gastrointestinal involvement, decreased sensation of pain and temperature in the hands and feet, e.g. Raynaud syndrome and other vascular disorders, attention deficit hyperactivity disorder (ADHD), depression and thin tooth enamel are associated with NPS, but the exact nature of these relationships remains not fully explained.[10] [11] [12]

General appearance (general phenotype) - it is possible and frequent to have lean body type (difficulty gaining weight even with a healthy and nutritious diet) and underdeveloped muscle mass, particularly in the limbs. It is most noticeable in young people with nail-patella syndrome, but not exclusively. Absence or underdevelopment of arm muscles (triceps, leading to thin structure of arms) and a high forehead - also may be present. [13] [14] However, low body weight sometimes can change (grow) with age, for example in women going through menopause, under the influence of other changes in metabolism, various medications and other factors. Eventual possible weight gain - later in life - does not necessarily have to be associated with an increase in muscle mass.

Nail-patella syndrome may cause diverse and not always uniform symptoms in individual patients - it is associated with high phenotypic variability, even in the same family. [15] In milder cases, some patients may only experience part of symptoms of this syndrome. Some potential symptoms (such as e.g. possible kidney damage or mentioned glaucoma) may appear and become more apparent with age and/or under the influence of additional aggravating factors. Other, than mentioned above, possible symptoms of NPS are also described in specialized sources, because the mutated gene can affect the entire body.

Genetics

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Nail–patella syndrome is inherited in an autosomal dominant pattern.

Nail–patella syndrome is inherited via autosomal dominancy linked to aberrancy on human chromosome 9's q arm (the longer arm), 9q34. This autosomal dominancy means that only a single copy, instead of both, is sufficient for the disorder to be expressed in the offspring, meaning the chance of getting the disorder from an affected heterozygous parent is 50%. The frequency of the occurrence is 1/50,000. The disorder is linked to the ABO blood group locus.[16]

It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified.[17][18][19]

Diagnosis

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The hallmark features of this syndrome are poorly developed fingernails (especially of thumbs) - in approximately 95 percent of patients, rarely - toenails (especially the smallest nail of feet), and hypoplastic or aplastic patellae (kneecaps) - in approximately 75 percent of patients. Sometimes, this disease causes the affected person to have either no thumbnails or a small piece of a thumbnail on the edge of the thumb. The lack of development or complete absence of fingernails results from the loss of function mutations in the LMX1B gene. A unique feature of this syndrome is also the triangular lunulae at the base of the fingernails - especially in NPS patients who have nails present (in healthy individuals, without NPS, lunulae are semicircular) [20]. This mutation may cause a reduction in dorsalising signals, which then results in the failure to normally develop dorsal specific structures such as nails and patellae.[21] Other common abnormalities include elbow deformities, kidney disease,[22] and abnormally shaped pelvic (hip) bones.[citation needed] Individual cases of this syndrome may be diverse and not fully symptomatic, as is the case with any genetic syndrome, they may also affect fitness and functioning of the body to varying degrees - from severe to mild cases (different mutations - pathogenic variants regarding other fragments/exons of the same gene and varying degrees of impact on the phenotype and areas of the body, even in the case of the same mutation in relatives in the same family).

Treatment

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Treatment for NPS varies depending on the symptoms observed.

See also

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References

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  1. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (1993). "Nail-Patella Syndrome". University of Washington, Seattle. PMID 20301311.
  2. ^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
  3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. Page 786-7. ISBN 0-7216-2921-0.
  4. ^ Choczaj-Kukula, A., & Janniger, C. K. (2009). Nail–patella syndrome. In emedicine: WebMD. Retrieved October 11, 2009, from WebMD database.
  5. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (14 December 2023). "Nail-Patella Syndrome". GeneReviews® [Internet]. University of Washington, Seattle. PMID 20301311.
  6. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (1993). "Nail-Patella Syndrome". University of Washington, Seattle. PMID 20301311.
  7. ^ "Syndrome Nail-Patella - Synthèse du PNDS à destination du médecin traitant".
  8. ^ Romero, P., Sanhueza, F., Lopez, P., Reyes, L., & Herrera, L. (2011). C.194 a>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma. Molecular Vision, 17(210-11), 1929–1939.
  9. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (1993). "Nail-Patella Syndrome". University of Washington, Seattle. PMID 20301311.
  10. ^ Buatti Chris (August 2007). "Nail-Patella Syndrome". Consultant 360. 47 (8).
  11. ^ "Nail-Patella Syndrome". GeneReviews®. University of Washington, Seattle. 1993. PMID 20301311.
  12. ^ López-Arvizu, C.; Sparrow, E. P.; Strube, M. J.; Slavin, C.; Deoleo, C.; James, J.; Hoover-Fong, J.; McIntosh, I.; Tierney, E. (2011). "Increased symptoms of attention deficit hyperactivity disorder and major depressive disorder symptoms in Nail-patella syndrome: Potential association with LMX1B loss-of-function". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication of the International Society of Psychiatric Genetics. 156B (1): 59–66. doi:10.1002/ajmg.b.31138. PMC 3677769. PMID 21184584.
  13. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (1993). "Nail-Patella Syndrome". University of Washington, Seattle. PMID 20301311.
  14. ^ "Monarch Initiative".
  15. ^ Adam, M. P.; Feldman, J.; Mirzaa, G. M.; Pagon, R. A.; Wallace, S. E.; Amemiya, A.; Sweeney, E.; Hoover-Fong, J. E.; McIntosh, I. (1993). "Nail-Patella Syndrome". University of Washington, Seattle. PMID 20301311.
  16. ^ RENWICK, J. H.; LAWLER, SYLVIA D. (1955). "Genetical Linkage Between the Abo and Nail-Patella Loci". Annals of Human Genetics. 19 (4): 312–331. doi:10.1111/j.1469-1809.1955.tb01356.x. ISSN 0003-4800. PMID 14388536. S2CID 30141328.
  17. ^ a b Sweeney E, Fryer A (March 2003). "Nail patella syndrome: a review of the phenotype aided by developmental biology". Journal of Medical Genetics. 40 (3): 153–162. doi:10.1136/jmg.40.3.153. PMC 1735400. PMID 12624132.
  18. ^ Towers AL, Clay CA, Sereika SM, McIntosh I, Greenspan SL (April 2005). "Skeletal integrity in patients with nail patella syndrome". J. Clin. Endocrinol. Metab. 90 (4): 1961–5. doi:10.1210/jc.2004-0997. PMID 15623820.
  19. ^ Romero P.; Sanhueza F.; Lopez P.; Reyes L.; Herrera L. (2011). "c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma". Molecular Vision. 17: 1929–39. PMC 3154131. PMID 21850167.
  20. ^ "Nail-Patella Syndrome". GeneReviews®. University of Washington, Seattle. 1993. PMID 20301311.
  21. ^ Wright M J (September 2000). "Achondroplasia and nail-patella syndrome: the compound phenotype". Journal of Medical Genetics. 37 (9): 25e–25. doi:10.1136/jmg.37.9.e25. PMC 1734684. PMID 10978372.
  22. ^ Sweeney, E.; Fryer, A.; Mountford, R.; Green, A.; McIntosh, I. (2003-03-01). "Nail patella syndrome: a review of the phenotype aided by developmental biology". Journal of Medical Genetics. 40 (3): 153–162. doi:10.1136/jmg.40.3.153. ISSN 0022-2593. PMC 1735400. PMID 12624132.
  23. ^ Kaplan's Essentials of Cardiac Anesthesia. Elsevier. 2018. doi:10.1016/c2012-0-06151-0. ISBN 978-0-323-49798-5.
  24. ^ Aronow, Wilbert S. (2010). "Cardiac Arrhythmias". Brocklehurst's Textbook of Geriatric Medicine and Gerontology. Elsevier. pp. 327–337. doi:10.1016/b978-1-4160-6231-8.10045-5. ISBN 978-1-4160-6231-8. Angiotensin-converting enzyme inhibitors ACE inhibitors have been demonstrated to reduce sudden cardiac death in some studies of persons with CHF.24,56
  25. ^ "Overview and Types of Dialysis". The Lecturio Medical Concept Library. Retrieved 27 August 2021.
  26. ^ "20 Common Kidney Transplant Questions and Answers". National Kidney Foundation. 26 January 2017. Archived from the original on 21 March 2021. Retrieved 23 March 2021.
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