Diagnosis Of Nail-patella Syndrome Research Articles

Chronic Knee Pain is the Paramount Presentation in Patients with Nail-Patella Syndrome

Background: Arthralgia in connection with patellar instability have been studied thoroughly in a number of pediatric and adult patients. Small and dysplastic patellae accompanied by hypoplasia of the lateral femoral condyle may results in recurrent subluxation or dislocation of the patellae, knee discomfort and pain. We aimed to detect the underlying etiology of every single patient. Patients and Methods: A total of seven children presented with long term painful knee joints have been refered from the departments of rheumatology. We added adult female patient of a-35-years-old. She was a chronic client of rheumatology clinics since her postadulthood. In addition to her early life knee pain. Recently she experienced additional chronic pain of the groin (located at the posterior buttocks). All our patients showed episodes of knee pain with variable intensity as a constant complaint and all received antirheumatic treatments for years despite the negative results of the implemented tests. In order to commence the diagnostic process, clinical and radiological phenotypic characterization were the main core of our stratregy followed by molecular genetic confirmation. Results: Seven unrelated children (aged from 8-17 years old) were consistent with the diagnosis of Nail- Patella syndrome. The adult female patient of a-35-years-old- manifested patellar instability since her early childhood. Her clinical phenotype was totally compatible with the diagnosis of Nail-Patella syndrome. Surprisingly, the clinical examination of the female patient and the standing AP pelvis radiograph revealed massive encroachment of the medial aspect of the femoral neck and the lesser trochanters onto the ischium. The latter resulted in the diagnosis of Ischiofemoral Impingement (IFI) syndrome. Her genetic tests showed heterozygous mutation in the LIM-homeodomain protein LMX1B on chromosome 9q33. Conclusion: Arthralgia associated with abnormal gait (mostly antalgic gait and waddling gait) was the paramount clinical presentation in all our patients. Dysplasia of the nails and patellar instability were the characteristic clinical findings in our patients with the definite diagnosis of osteo-onychodysplasia syndrome. We approached to the diagnosis from the first session of clinical examination. Interestingly, the constant groin pain in the adult female patient which has been totally overlooked by other instutions, were in favor of the diagnosis of Ischiofemoral Impingement (IFI) syndrome. As well as the existing abnormality of the elbows associated with defective pronation and supination as due to impingement of the olecranon. The task of establishing the diagnostic process in complex clinical conditions is the most challenging. Sadly speaking, none of the aforemnetioned dignostic criteria attracted the attention of dozens of clinicians. Admistering medications to overcome knee pain through dozens of useless laboratory tests were the main false issue. Clinicians who are actively involved in clinical diagnosis with minimal dependency on laboratory aid are generally at the forefront of their medical fields.

Chronic Knee Pain is the Paramount Presentation in Patients with Nail-Patella Syndrome

Background: Arthralgia in connection with patellar instability have been studied thoroughly in a number of pediatric and adult patients. Small and dysplastic patellae accompanied by hypoplasia of the lateral femoral condyle may results in recurrent subluxation or dislocation of the patellae, knee discomfort and pain. We aimed to detect the underlying etiology of every single patient. Patients and Methods: A total of seven children presented with long term painful knee joints have been refered from the departments of rheumatology. We added adult female patient of a-35-years-old. She was a chronic client of rheumatology clinics since her postadulthood. In addition to her early life knee pain. Recently she experienced additional chronic pain of the groin (located at the posterior buttocks). All our patients showed episodes of knee pain with variable intensity as a constant complaint and all received antirheumatic treatments for years despite the negative results of the implemented tests. In order to commence the diagnostic process, clinical and radiological phenotypic characterization were the main core of our stratregy followed by molecular genetic confirmation. Results: Seven unrelated children (aged from 8-17 years old) were consistent with the diagnosis of Nail- Patella syndrome. The adult female patient of a-35-years-old- manifested patellar instability since her early childhood. Her clinical phenotype was totally compatible with the diagnosis of Nail-Patella syndrome. Surprisingly, the clinical examination of the female patient and the standing AP pelvis radiograph revealed massive encroachment of the medial aspect of the femoral neck and the lesser trochanters onto the ischium. The latter resulted in the diagnosis of Ischiofemoral Impingement (IFI) syndrome. Her genetic tests showed heterozygous mutation in the LIM-homeodomain protein LMX1B on chromosome 9q33. Conclusion: Arthralgia associated with abnormal gait (mostly antalgic gait and waddling gait) was the paramount clinical presentation in all our patients. Dysplasia of the nails and patellar instability were the characteristic clinical findings in our patients with the definite diagnosis of osteo-onychodysplasia syndrome. We approached to the diagnosis from the first session of clinical examination. Interestingly, the constant groin pain in the adult female patient which has been totally overlooked by other instutions, were in favor of the diagnosis of Ischiofemoral Impingement (IFI) syndrome. As well as the existing abnormality of the elbows associated with defective pronation and supination as due to impingement of the olecranon. The task of establishing the diagnostic process in complex clinical conditions is the most challenging. Sadly speaking, none of the aforemnetioned dignostic criteria attracted the attention of dozens of clinicians. Admistering medications to overcome knee pain through dozens of useless laboratory tests were the main false issue. Clinicians who are actively involved in clinical diagnosis with minimal dependency on laboratory aid are generally at the forefront of their medical fields.

Nail-Patella syndrome with early onset end-stage renal disease in a child with a novel heterozygous missense mutation in the LMX1B homeodomain: A case report.

Nail-Patella syndrome (NPS) is an inherited disease characterized by nail and skeletal anomalies, nephropathy and glaucoma. The diagnosis of NPS is based on clinical findings, including hypoplastic or absent patella, dystrophic nails, dysplasia of the elbows and iliac horns. However, the main determinant of NPS prognosis is nephropathy, which may range from asymptomatic proteinuria to end-stage renal disease. NPS is caused by heterozygous loss-of-function mutations in the LMX1B gene, which encodes the LIM homeodomain transcription factor LMX1B. LMX1B serves an essential role in the physiological development of dorsal-ventral limb structures, morphogenesis and function of podocytes, as well as in development of the anterior segments of the eyes, and in certain types of neurons. The present study aimed to identify the disease-causing mutation in a 2-year old girl with nephrotic syndrome that evolved rapidly to end-stage renal disease. The patient showed classical symptoms of NPS including dystrophic nails and an absence of the patellae. DNA sequence analysis identified a novel missense variant in exon 4 of LMX1B (c.709T>C, p.S237P); this substitution affected a conserved serine residue in the homeodomain of LMX1B and was predicted to be pathogenic. In silico modeling of the homeodomain revealed that the p.S237P mutation converted the A236-S237-F238 segment of α-helix 1 into a strand. It was hypothesized that this mutation affected binding of the transcription factor to its target DNA, thus abrogating transcription activation, which would explain the phenotype that manifested in the patient.

Prenatal diagnosis of nail patella syndrome: A case report

The Nail Patella Syndrome (NPS) is an autosomal dominant connective tissue disorder affecting the nails, skeletal system, kidneys and eyes. Here, we report a case of NPS detected at 19 weeks of gestation. The movements of the elbow and knee joints were restricted and there was rotational deformity of the knee joints. To our knowledge, this is the first report of in-utero restriction of limb movements in a fetus with NPS.

Treatment of patellar instability in a case of hereditary onycho-osteodysplasia (nail-patella syndrome) with medial patellofemoral ligament reconstruction: A case report.

Hereditary onycho-osteodysplasia, also known as nail-patella syndrome (NPS), is a rare genetic disorder that is primarily characterized by poorly developed nails and patella. Patients with NPS frequently suffer from patellar instability that requires surgical management. The present case report describes a 25-year-old man with NPS. The patient presented with left knee pain and was found to have recurrent left patellar dislocation. The knee pain was first reported 1-year after a minor knee trauma incident. Following complete evaluation, a diagnosis of NPS was reached. The patient underwent surgical intervention using medial patellofemoral ligament (MPFL) reconstruction with a gracilis tendon autograft looped through two transverse 3.2-mm drill holes in the patella and fixed at the natural MPFL insertion site on the medial femoral condyle with an interference screw. The surgery resulted in stabilization of the patella in the femoral trochlea and the patient did not have any subsequent dislocations or subluxations. The patient had an excellent range of knee movement in the follow-up period. This case indicates that MPFL reconstruction in patients with patellar dislocation secondary to NPS can successfully restore normal patellar tracking and result in good range of movement and functional activity.

Neurophysiology (EMG)

Background: Nail-patella syndrome (NPS) is an inherited autosomal dominant disease, with an incidence of approximately 1 in 50,000. It ischaracterized by nail dysplasia, hypoplastic patellae, other bone deformities and open angle glaucoma. The phenotype is variable. Methods: Case report Results: A 66 year old male presented with complaints of mild loss of sensation in both feet with gradual proximal spread to his knees over the past decade. There was no history of pain, paresthesias, autonomic dysfunction or weakness. Examination showed pectus excavatum with symmetrically dystrophic fingernails. Sensation to crude touch, pain and temperature were reduced up to mid shin, and vibration sense was diminished till the malleoli symmetrically. Electrophysiologic studies revealed a mild to moderate length-dependent polyneuropathy of axonal type. Detailed blood screening studies were negative. Genetic testing revealed the diagnosis of nail-patella syndrome with LMX1B gene mutation on chromosome 9q34. The lack of an identifiable acquired cause and the symmetric, slowly progressive and “painless” nature of the patient’s peripheral neuropathy point toward an inherited etiology. Conclusion: We present a case of slowly progressive sensorimotor axonal polyneuropathy in a patient with a diagnosis of NPS, which has not been previously reported. Peripheral nervous system disorder may be a variable phenotypic manifestation of LMX1B gene mutation.

GE-13 * A NOVEL ASSOCIATION OF PRIMARY CNS GERMINOMA IN A PATIENT WITH NAIL PATELLA SYNDROME

Nail patella syndrome (NPS) is an autosomal dominant disorder with a prevalence of 1/50,000 characterized by developmental abnormalities of the nails, knees and elbows, as well as renal dysplasia and open angle glaucoma. NPS is caused by a mutation in the LMX1B gene, a transcription factor involved in ventral/dorsal patterning of the vertebrate limb. While malignancy is rare in patients with NPS, Ewing's sarcoma and colon cancer have been reported. Additionally, NPS has been described in a 5 generation family with neurofibromatosis type 1. We report a novel association of NPS with primary CNS germinoma. A 22-year-old male presented with a two-month history of diabetes insipidus (DI) and headaches. Physical examination revealed partial Parinaud's syndrome, dystrophic nails and surgical repair of left hypoplastic patella. Because the family history revealed numerous maternal family members with dystrophic nails and hypoplastic patellae, we subsequently made a formal clinical diagnosis of NPS. Contrast enhanced MRI of the brain revealed an enhancing cystic pineal mass and a Chiari I malformation; serum and CSF alpha-fetoprotein and beta-human chorionic gonadotropin were negative. Biopsy of the pineal mass was consistent with pure germinoma for which the patient received external beam radiation therapy via intensity modulated radiation therapy (IMRT) as follows: 1) 2520 cGy to the craniospinal axis; 2) 5040 cGy to the pineal region; 3) and 4620 cGy to the suprasellar region (for presumed tumor in the posterior pituitary given the history of DI). He remains in remission 9 years post-treatment. For the NPS, the patient declined referral to genetics due to insurance concerns but he and his family have been referred to appropriate services for screening of other abnormalities associated with the syndrome. This case report suggests that LMX1B may play a role in the development of CNS germinoma.

Bilateral absence of the patella in nail-patella syndrome: Delayed presentation with anterior knee instability

<h3>Abstract</h3> A 27-year-old man, while serving in the armed forces, presented with complaints of right knee pain of 3 months duration. The patient reported pain localized on the lateral side of the right knee, especially during long-distance walking and stair climbing, and a feeling of giving way. There was no history of recent or remote trauma to the knee joint. At that time, he presented with knee pain and instability consistent with anterior cruciate ligament (ACL) insufficiency. During physical examination, the diagnosis of nail-patella syndrome (NPS) was made, but magnetic resonance imaging (MRI) of both knees revealed intact ACLs. The reported case presents NPS as a potential nontraumatic cause of anterior knee instability. In our patient, a discrepancy between the clinical and imaging findings was present. The initial clinical examination was consistent with ACL rupture or aplasia and this led to MRI evaluation of the knee, which showed an intact ACL, contrary to the initial diagnosis. It should be noted that anterior instability has been described after patellectomy and could be attributed to complete absence of the patella, which is rare in NPS.

Collagen type III glomerulopathy: a new type of hereditary nephropathy

A new type of hereditary glomerulopathy was observed in ten children presenting with early and progressive glomerular symptoms, often associated with hypertension. Light microscopy showed a diffuse increase in the mesangial matrix and generalized widening of the capillary walls. Electron-microscopic examination of renal tissue, after phosphotungstic acid treatment, revealed the presence of fibrillar collagen within the mesangial matrix and the subendothelial aspect of the glomerular basement membrane, adjacent to normal lamina densa. Immunohistochemical studies identified the fibrillar collagen not usually present within the glomerular extracellular matrix as type III collagen. Clinical and family studies ruled out the diagnosis of nail-patella syndrome, an autosomal dominant disorder with typical extrarenal symptoms, which is also characterized by the presence of fibrillar collagen within the glomerular basement membranes. The poor renal outcome, the possible extrarenal haematological and pulmonary involvement and the transmission as an autosomal recessive trait strongly suggest that collagen type III glomerulopathy is a new type of hereditary disease. From the high incidence of superimposed haemolytic uraemic syndrome in patients or their siblings, it may be hypothesized that collagen type III glomerulopathy is the underlying defect in some of the familial cases of haemolytic uraemic syndromes.

Ulnarisirritation am Ellenbogen bei Nail-Patella-Syndrom

The nail-patella syndrome (NPS) is marked by bony irregularities (dysplasia of the elbows and patella, iliacal horns) and cutaneous disturbances (dystrophies of the radial nails of fingers and toes). It is of autosomal dominant heredity. The NPS is associated with glomerular nephritis. We describe a patient in whom, due to clinical and radiological features, a classical NPS could be evaluated. Different members of the family are also involved. The 38-year old woman additionally shows a compression syndrome of the n. ulnaris at the deformed elbow on both sides. The nerve disturbance was already before the diagnosis of NPS had been confirmed. Our case report may lead to the detection of further patients with NPS in cases where a compression of the n. ulnaris on both sides is found without typical, pathogenetic factors. This may lead to genetic advices for the patient and, especially in cases of gravidity, to an increased attention of renal function.