What is it?
Nail Patella Syndrome (otherwise known as Fong's Disease, Hereditary Onychoosteodysplasia ["HOOD"] or Turner-Kieser Syndrome) is an autosomal dominant condition closely linked to the ABO blood group. The gene is located on chromosome 9q34 and is called LMX1B. The risk of gene transmission is 50% per pregnancy, irrespective of gender. It is estimated to occur in 1 in 50,000 newborns.
Nail Patella Syndrome is a complex condition that varies greatly between each individual. This is aimed to provide the correct documented evidence to each specialist field of medicine and to aid in the treatments and surgical decisions that may need to be made. It is hoped also to provide the reader with a source of contact regarding many aspects of the syndrome.
Orthopedics, Nephrology, Opthalmology and Genetics have been highlighted as these are the specialist fields of medicine commonly associated with NPS. There are many other areas that should be included, for example Rheumatology, but for the moment we should concentrate on the four mentioned above.
ORTHOPEDICS
In 1820 Chatelain first reported a link between nail abnormalities and skeletal dysplasia.
Nails:
Classically, there is an absence of the thumbnail and or other nails; dysplasia of the finger/toe nails, usually thumbnail; underdeveloped or triangular lunulae, discoloration and longitudinal ridging; splitting and cracking.
Patellae:
Aplasia (absence) or hypoplasia (underdeveloped) patella.The patella may be located more distally than the average knee superimposed on both the femoral and lateral tibia condyles resulting in recurrence of dislocation. The patella may be ovoid, triangular or irregular in shape.
Pelvis:
Exostoses ('horns") of the ilia are often apparent, with crests or spurs also having been reported; abnormal projections of bone from the superior (upper) portion of both sides of the hip bone (bilateral iliac horns). These "horns" are unique to our species and this condition. They may be visible, palpable or impalpable, depending on size.
Elbows:
Often there is an obvious incomplete extension due to dislocation of the elbow joints; hypoplastic capitellum and small head of radius; contractures (stiffening around the joints); underdevelopment of certain bones and/or webbing of the skin at the bend of the elbow; the mobility of the wrist can also be restricted, especially in rotation; dislocation is also reported at the shoulder joints.
Other frequent features:
Hypoplasia of the scapulae. A thick, convex outer border can often be found. Talipes (club foot) or "twisted feet".
Occasional abnormalities
Hypoplasia of the first ribs Dislocation of the head of the radius Prominent outer clavicle Malformed sternum (Pectus Excavatum) Scoliosis Lordosis Spine abnormalities, often resulting in spinal fusion surgery
There is also aplasia of pectoralis minor, biceps, triceps and quadriceps.
Nephrology
The incidence of renal impairment in NPS is approximately 30-50%. This is more apparent later in life, although there are reports of early renal problems in childhood. Protienuria with or without hematuria often manifests itself. Nephrotic syndrome and progressive renal failure can occur. The glomerular changes by light microscopy are quite non-specific, varying in degrees of focal and segmented sclerosis and often segmented thickening of the capillary wall. The microscopy reveals a unique lesion consisting of a moth-eaten appearance of the glomerular basement membrane. This condition is said to be a generalised disorder of the mesenchyme. The course is rather benign with renal failure a late feature.
Routine urine tests are usually carried out (usually on an annual basis). Occasionally, a small specimen of kidney (biopsy) is necessary to establish how severely the kidneys are affected. Sometimes limb swelling due to water retention can occur (oedema). If a transplant is deemed necessary, it should be noted that the kidney disease does nor reoccur.
Opthalmology
Researchers at the University of Michigan Health System have found strong evidence of a link between glaucoma and NPS. Studies suggest indirect evidence that the genetic location of the two conditions may be located at the same chromosomal site. The studies suggest a need for opthalmological examinations for people with NPS.
Open angle glaucoma can be described as a condition caused by progressive blockage of the outflow of fluid from the front chamber of the eyes. If this is left untreated, the increase in fluid pressure may cause narrowed vision and eventual blindness.
Other ocular abnormalities that have been reported are:
Keratoconus Microcornea Microphakia Cataracts Ptosis
Genetics
At the Johns Hopkins University in Baltimore, Maryland, a great deal of research has been done to establish the gene and to look at various aspects of NPS and why there are so many differences between individuals.
The gene has now been identified as a result of much detailed research. The gene is called LMX1B and controls a protein that has been implicated in the dorsoventral patterning of the developing limb bud. When only one copy of this gene is inherited, only half the protein is produced. Recent research is looking to explain why the phenotype of LMX1B deficiency differs greatly even within families.
As the gene has now been mapped, it is now possible to perform pre-natal diagnosis for couples who do not want to pass the syndrome to their children. This diagnosis requires a chorionic villus sampling to be taken at about 10 weeks of gestation. By comparing the foetal DNA with that from the parents it is possible to determine whether NPS has been inherited. It is, however, not possible to determine how severe the NPS will be.
A future option is pre-implantation diagnosis. Once the NPS gene is identified, theoretically it will be possible to determine the affected state of the embryo at the 8-cell stage of development. The embryos would be generated by IVF techniques. This procedure is still experimental and has a high error rate.
Another possibility includes the use of sperm or egg donors. This would mean that the child would receive no genes from the affected parent.
Possible links
Dental Problems Hyperthyroidism Gastro-intestinal problems Irritable bowel syndrome Tilted uterus Smaller stat +0ure Cleft lip/palate Widow's peak
NPS also causes severe pain in many cases and often individuals are forced to take pain relief.
References
Little EM: Congenital absence or delayed development of patella, Lancet, 2:781, 1997 Carbonara P and Alpert M: Hereditary Onychoosteodysplasia (HOOD), Am. J. Med. Sci., 248:189, 1964 Daniel CR, Osment LS, and Noojin RO: Triangular Lunulae: Arch. Dermatol., 116:448, 1980 Rizzo R, et al.: Severe renal involvement in Nail Patella Syndrome: Clin. Genet., 44:1, 1993 McIntosh I et al: Mutation analysis of LMX1B gene in Nail Patella Syndrome Patients, Am. J. Hum. Genet., 63:1651 1998
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It appears that a number of us have inherited this condition, almost certainly from John Beck (my grandfather), but I don't know from which side of his family it originated, or whether his was a spontaneous mutation.
I've printed the "dry" stuff above - you might want to copy it to take to your doctor. On the "links" page, you will find that you can go to sites belonging to the world NPS group and the UK NPS group, which contain more information and even more links. There is a discussion/support group which you might enjoy - it has members from all over, though mainly from the US and the UK and the community spirit is amazing. The topics discussed are not confined to NPS - if you want to join, you'll find details on the sites mentioned above, or find it on the Yahoo groups site under "Health".
It's not my intention to cause alarm by publicising this information - most people with NPS don't have every symptom and very few have severe kidney problems ; but if the gene is present in your blood and if you have strange fingernails, bent elbows or wonky knees, you should make sure that your kidneys are monitored on a regular basis and that you have the full glaucoma test every year. Then there are suitable exercises for people with NPS, geared to joint abnormalities ; if those cause problems, it's important that any orthopaedic consultant knows that this syndrome is present before undertaking any treatment. The bottom line is that I want to make sure that everyone in our family with this condition has all the information they need and that they can educate their GPs (because not every doctor knows about NPS - it is a fairly rare condition.)
E-mail me if you have any more questions and I'll do my best to help.
Link to a useful website and another