Nail–patella syndrome

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| name = Nail–patella syndrome

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| caption = Nail of a patient with nail–patella syndrome

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| synonyms = NPS

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| causes =mutations in the LMX1B gene.

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Nail–patella syndrome is a genetic disorder that results in small, poorly developed nails and kneecaps, but can also affect many other areas of the body, such as the elbows, chest, and hips. The name "nail–patella" can be very misleading because the syndrome often affects many other areas of the body, including even the production of certain proteins.Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. {{ISBN|0-07-138076-0}}.{{rp|666}} 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.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}}.

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.

Signs and symptoms

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:Choczaj-Kukula, A., & Janniger, C. K. (2009). Nail–patella syndrome. In emedicine: WebMD. Retrieved October 11, 2009, from WebMD database.

Bones and joints{{citation needed|date=September 2021}}

File:Patella radiograph in Nail Patella Syndrome.jpg

File:Posterior iliac horn.jpg

Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%.
In instances in which the patellae are smaller or luxated, the knees may be unstable.
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 90% of patients.
General hyperextension of the joints can be present.
Exostoses arising from the posterior aspect of the iliac bones ("iliac horns") are present in as many as 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.

File:Nail-patella syndrome (NPS) Elbow1.JPG|An elbow of a man with nail–patella syndrome (NPS)

File:Nail-patella Elbow2.JPG|This is a view from a different angle of the same man's other elbow

File:Nail-patella.jpg|link=|alt=

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.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.

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 5% of NPS patients. Hypothyroidism, irritable bowel syndrome, attention deficit hyperactivity disorder (ADHD), and thin tooth enamel are associated with NPS, but whether these are related or simply coincidences are unclear.{{cite journal |author=Buatti Chris |title=Nail-Patella Syndrome |journal=Consultant 360 |volume=47 |issue=8 |date=August 2007 |url= http://www.consultant360.com/content/nail-patella-syndrome}}

Genetics

File:Autosomal dominant - en.svg 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.{{Cite journal |last1=RENWICK |first1=J. H. |last2=LAWLER |first2=SYLVIA D. |title=Genetical Linkage Between the Abo and Nail-Patella Loci |date=1955 |url=http://dx.doi.org/10.1111/j.1469-1809.1955.tb01356.x |journal=Annals of Human Genetics |volume=19 |issue=4 |pages=312–331 |doi=10.1111/j.1469-1809.1955.tb01356.x |pmid=14388536 |s2cid=30141328 |issn=0003-4800}}

It is associated with random mutations in the LMX1B gene. Studies have been conducted and 83 mutations of this gene have been identified.{{cite journal |vauthors=Towers AL, Clay CA, Sereika SM, McIntosh I, Greenspan SL |title=Skeletal integrity in patients with nail patella syndrome |journal=J. Clin. Endocrinol. Metab. |volume=90 |issue=4 |pages=1961–5 |date=April 2005 |pmid=15623820 |doi=10.1210/jc.2004-0997 |doi-access=free }}{{cite journal|author1=Romero P. |author2=Sanhueza F. |author3=Lopez P. |author4=Reyes L. |author5=Herrera L. |title=c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma|journal=Molecular Vision|date=2011|volume=17|pages=1929–39|pmid=21850167|pmc=3154131}}

Diagnosis

The hallmark features of this syndrome are poorly developed fingernails, toenails, and patellae (kneecaps). 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. 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.{{cite journal |author=Wright M J |title=Achondroplasia and nail-patella syndrome: the compound phenotype |journal=Journal of Medical Genetics |volume=37 |issue=9 |pages=25e–25 |doi=10.1136/jmg.37.9.e25 |pmid=10978372 |pmc=1734684 |date=September 2000 }} Other common abnormalities include elbow deformities, kidney disease,{{Cite journal |last1=Sweeney |first1=E. |last2=Fryer |first2=A. |last3=Mountford |first3=R. |last4=Green |first4=A. |last5=McIntosh |first5=I. |date=2003-03-01 |title=Nail patella syndrome: a review of the phenotype aided by developmental biology |url=https://jmg.bmj.com/content/40/3/153 |journal=Journal of Medical Genetics |language=en |volume=40 |issue=3 |pages=153–162 |doi=10.1136/jmg.40.3.153 |issn=0022-2593 |pmid=12624132|pmc=1735400 }} and abnormally shaped pelvic (hip) bones.{{citation needed|date=September 2020}}

Treatment

Treatment for NPS varies depending on the symptoms observed.

Perform screening for kidney disease and glaucoma, surgery, intensive physiotherapy, or genetic counseling.{{cite journal |vauthors=Sweeney E, Fryer A |title=Nail patella syndrome: a review of the phenotype aided by developmental biology|journal=Journal of Medical Genetics |volume=40 |issue=3 |pages=153–162 |doi=10.1136/jmg.40.3.153|pmid=12624132|pmc=1735400|date=March 2003}}
ACE inhibitors are taken to treat proteinuria and hypertension in NPS patients.{{cite book | title=Kaplan's Essentials of Cardiac Anesthesia | publisher=Elsevier | year=2018 | isbn=978-0-323-49798-5 | doi=10.1016/c2012-0-06151-0 }}{{cite book | last=Aronow | first=Wilbert S. | title=Brocklehurst's Textbook of Geriatric Medicine and Gerontology | chapter=Cardiac Arrhythmias | publisher=Elsevier | year=2010 | isbn=978-1-4160-6231-8 | doi=10.1016/b978-1-4160-6231-8.10045-5 | pages=327–337 | quote=Angiotensin-converting enzyme inhibitors ACE inhibitors have been demonstrated to reduce sudden cardiac death in some studies of persons with CHF.24,56}}
Dialysis and kidney transplant.{{cite web |url= https://www.lecturio.com/concepts/overview-and-types-of-dialysis/| title= Overview and Types of Dialysis

|website=The Lecturio Medical Concept Library |access-date= 27 August 2021}}{{cite web | url = https://www.kidney.org/atoz/content/kidney-transplant| title = 20 Common Kidney Transplant Questions and Answers | author = | date = 26 January 2017 | publisher = National Kidney Foundation | archive-url = https://web.archive.org/web/20210321124806/https://www.kidney.org/atoz/content/kidney-transplant | archive-date = 21 March 2021 | url-status =live | access-date = 23 March 2021}}