Nail-Patella Syndrome
Nail-Patella Syndrome (NPS)
Nail-Patella Syndrome (NPS), also known as hereditary osteo-onychodysplasia (HOOD) or Fong disease, is a rare genetic disorder affecting multiple body systems, primarily the nails, skeletal system, and kidneys. It is characterized by nail dysplasia, patellar abnormalities, elbow dysplasia, and iliac horns.
Key Points:
- Autosomal dominant inheritance
- Caused by mutations in the LMX1B gene
- Prevalence: 1 in 50,000 live births
- Variable expressivity and penetrance
- Affects multiple organ systems: skeletal, renal, ocular, and neurological
Clinical Features
Nail Abnormalities:
- Hypoplastic or absent fingernails, especially the thumbnails
- Triangular lunulae
- Splitting or ridging of nails
Skeletal Abnormalities:
- Absent, hypoplastic, or dislocated patellae
- Iliac horns (pathognomonic radiographic finding)
- Elbow dysplasia with limited range of motion
- Pelvic asymmetry
- Talipes equinovarus (clubfoot)
Renal Involvement:
- Proteinuria
- Hematuria
- Renal insufficiency or failure (in ~30% of cases)
Ocular Findings:
- Open-angle glaucoma
- Ocular hypertension
- Iris hyperpigmentation (Lester's sign)
Other Features:
- Gastrointestinal problems (irritable bowel syndrome, constipation)
- Neurological symptoms (numbness, tingling, burning sensations)
- Dental abnormalities
Diagnosis
Diagnosis of Nail-Patella Syndrome is based on clinical findings, radiographic evidence, and genetic testing.
Clinical Diagnosis:
- Presence of characteristic nail and patellar abnormalities
- Family history consistent with autosomal dominant inheritance
Radiographic Findings:
- Iliac horns (pathognomonic)
- Absent or hypoplastic patellae
- Elbow abnormalities (radial head subluxation, hypoplasia of capitellum)
Genetic Testing:
- Molecular genetic testing for LMX1B gene mutations
- Sequence analysis and deletion/duplication analysis
Differential Diagnosis:
- Small patella syndrome
- Meier-Gorlin syndrome
- RAPADILINO syndrome
Management
Management of Nail-Patella Syndrome is multidisciplinary and focuses on symptom management and prevention of complications.
Orthopedic Management:
- Physical therapy for joint mobility and strength
- Orthopedic surgery for severe patellar or elbow abnormalities
- Custom orthotics for foot deformities
Renal Management:
- Regular monitoring of renal function and proteinuria
- ACE inhibitors or ARBs for proteinuria
- Renal replacement therapy for end-stage renal disease
Ophthalmologic Care:
- Regular eye examinations for glaucoma screening
- Intraocular pressure management as needed
Genetic Counseling:
- Discuss inheritance pattern and recurrence risk
- Offer prenatal testing options
Pain Management:
- NSAIDs for joint pain
- Neuropathic pain medications for neurological symptoms
Genetics
Inheritance Pattern:
- Autosomal dominant
- 50% chance of transmission to offspring
Genetic Basis:
- Mutations in the LMX1B gene (chromosome 9q33.3)
- LMX1B encodes a LIM-homeodomain transcription factor
- Essential for dorsal-ventral patterning of limbs and kidney development
Genotype-Phenotype Correlations:
- Variable expressivity even within families
- No clear correlation between specific mutations and severity of symptoms
Molecular Mechanisms:
- Haploinsufficiency is the primary disease mechanism
- Some mutations may have dominant-negative effects
