Part III: Nail-Patella Syndrome

A 35 year-old Caucasian female presented to clinic for a skin cancer screening examination. She had chronic gastrointestinal problems including reflux, bloating, constipation, and diarrhea. She had also experienced right arm numbness, especially with flexion, in addition to abnormal sensations in her feet and had difficulty standing in one position for long periods of time. Cold weather caused pain and color changes in her fingers. Additionally, she was on chronic vitamin D supplementation with a history of nontraumatic bone fracture. Calcium supplements were avoided given her gastrointestinal symptoms.

Her hypertension had been treated with an ACE inhibitor. She was a smoker and also has hyperlipidemia. Of note, she and her father have glaucoma and her paternal grandmother developed blindness at a young age however she does not know much additional family history.

On physical examination, she is unable to supinate her forearms and has a swan-neck appearance of multiple digits. Firm protrusions can be palpated along her bilateral lateral lower back. She has nail dysplasia involving her thumbnails and 2^nd digits in addition to triangular lunulae involving most fingernails. Interestingly, her daughter has similar physical findings.

Nail patella syndrome (NPS) (also known as hereditary osteo-onychodysplasia, Turner-Keiser syndrome, Fong disease, and nail-patella-elbow syndrome) is an inherited, autosomal dominant disorder that affects the limbs, eyes, kidneys, and nails.^2,4 It is relatively rare with a prevalence of 1:50,000.² The syndrome was first described in the 19^th century and is due to a mutation in LMX1B, a transcription factor important for regulating the development of nail, bone, and glomerular basement membrane.^6,4 This gene is also necessary for the normal functioning of renal glomerular podocytes as it maintains their actin cytoskeleton.¹

This condition is not life threatening however it may cause functional impairments and morbidity related to bone abnormalities, impaired renal function, and glaucoma. The dermatologic findings include various nail dystrophies and have aesthetic implications. Nail involvement occurs in 98% of patients, is typically symmetrical and often more severe from 2^nd to 5^th fingernails. These patients may have triangular lunulae, severe nail dysplasia, and micronychia in addition to absence of the medial and distal aspects of the thumb and 2^nd digit fingernails.⁴

Iliac horns are pathognomonic for nail-patella syndrome and contain cortex and medulla continuous with the iliac bone. The gluteus medius muscle insertion site marks their location and from this point they protrude posterolaterally. They are frequently palpated during physical examination however should have no impact on the patients' gait.³ The patellae may be hypoplastic or completely absent and patients may complain of knee pain. Dysplasia of the radial heads is also seen and may lead to the inability of forearm supination.⁴ Not specific to NPS, swan neck deformities of the fingers may be present and are due to hyperextension at proximal interphalangeal joints in addition to flexion at distal interphalangeal joints.² Although patients with NPS may not have an increased risk of osteopenia or osteoporosis, they have been found to have decreased bone mineral density and increased prevalence of fractures, particularly involving long bones of prepubertal women.⁷

Renal involvement is present in up to 60% of patients with NPS. Like our patient, many develop hypertension. Although most