Nail–patella syndrome

Overview

Nail–patella syndrome (NPS), also known as hereditary onycho-osteodysplasia, is a rare genetic disorder that affects the development of the nails, bones, kidneys, and eyes. The condition is named for its two hallmark features: abnormal fingernails and toenails, and underdeveloped or absent kneecaps (patellae). NPS belongs to a group of disorders known as pleiotropic disorders because it affects multiple organ systems with variable severity. Although it is present from birth, the degree to which symptoms manifest can differ widely even among affected individuals within the same family.

The syndrome is often recognized due to its distinctive nail abnormalities, but it can also lead to serious complications such as kidney disease and glaucoma. Because of its wide range of manifestations, early diagnosis and careful monitoring are essential for managing long-term outcomes.

Causes

Nail–patella syndrome is caused by mutations in the LMX1B gene, which provides instructions for making a transcription factor involved in limb, kidney, and eye development. This gene plays a crucial role during embryogenesis, particularly in the patterning and growth of the dorsal side (back side) of the body.

NPS follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene passed from one affected parent is sufficient to cause the disorder. In approximately 12.5% of cases, the mutation arises de novo, meaning it occurs for the first time in the affected individual with no family history.

Symptoms

The clinical presentation of NPS can vary greatly, but most individuals exhibit a combination of the following features:

Nail Abnormalities

• Small, ridged, pitted, or absent fingernails and toenails

• Triangular-shaped lunula (the white crescent at the base of the nail)

• More pronounced changes in thumbnails and less in toenails

Skeletal Abnormalities

• Absent or hypoplastic (underdeveloped) patellae, leading to knee instability

• Elbow deformities, limited extension or rotation

• Iliac horns (bony projections on the pelvic bones seen on X-ray and unique to NPS)

• Joint pain or hypermobility

Kidney Involvement

• Proteinuria (protein in urine), often the first sign of kidney issues

• Hematuria (blood in urine)

• Focal segmental glomerulosclerosis (FSGS), which can progress to kidney failure

• Variable onset—from early childhood to adulthood

Eye Issues

• Increased risk of open-angle glaucoma

• Occasional ocular hypertension

• Requires lifelong monitoring

Other Possible Features

• Dental anomalies such as misaligned or small teeth

• Clavicle or shoulder blade abnormalities

• Learning difficulties in some individuals (though not directly caused by the gene mutation)

Diagnosis

Diagnosis of Nail–patella syndrome is usually based on clinical findings and confirmed through genetic testing. The process may include:

• Clinical examination: Observation of nail dysplasia, skeletal anomalies, and family history

• Radiographic imaging: X-rays of knees, elbows, and pelvis to detect hypoplastic patellae or iliac horns

• Urinalysis: To detect protein or blood in urine, indicating kidney involvement

• Ophthalmologic exam: Screening for glaucoma and intraocular pressure monitoring

• Genetic testing: Sequencing of the LMX1B gene confirms the diagnosis, especially in ambiguous cases

Treatment

There is no cure for Nail–patella syndrome, but treatment focuses on symptom management and preventing complications. A multidisciplinary team often includes nephrologists, orthopedists, dermatologists, and ophthalmologists. Management strategies include:

• Orthopedic support: Braces, physical therapy, or surgical intervention for knee instability or joint deformities

• Kidney management: ACE inhibitors or ARBs to manage proteinuria; regular kidney function monitoring; dialysis or transplant in severe cases

• Ophthalmic care: Regular glaucoma screening; early treatment with medications or surgery if intraocular pressure is elevated

• Nail care: Protective measures to prevent damage to fragile or malformed nails

• Genetic counseling: Recommended for affected individuals and families to understand inheritance risks and reproductive options

Prognosis

The prognosis for individuals with Nail–patella syndrome varies depending on the extent of organ involvement, particularly the kidneys. Many people live normal lives with only mild nail or skeletal abnormalities. However, those with kidney complications may develop progressive renal disease, which requires lifelong monitoring and, in severe cases, dialysis or transplantation.

With appropriate care and early intervention, especially for orthopedic and renal issues, most individuals can maintain a good quality of life. Regular follow-ups with specialists are crucial to detect and manage any emerging complications promptly.