Genetics of Nail-Patella Syndrome Clinical Presentation

Updated: Dec 08, 2021
  • Author: Julie Hoover-Fong, MD, PhD, FACMG; Chief Editor: Maria Descartes, MD  more...
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See the list below:

  • Family history: Collect a full 3 generation pedigree to detect family history of autosomal dominant nail-patella syndrome (NPS). Currently, 88% of affected individuals have a positive family history of nail-patella syndrome. Nail-patella syndrome is fully penetrant, but significant interfamilial and intrafamilial variability is noted.

  • Nail/digit anomalies: Nail anomalies are present at birth.

  • Knees: Recurrent patellar dislocations, deformity of knee joint, and knee pain are noted.

  • Elbows: Elbow pain, decreased flexion, pronation, and supination are reported.

  • Back pain: This is common in nail-patella syndrome; underlying spinal problems such as spondylolisthesis may be observed.

  • Renal disease: Proteinuria, hypertension, and/or decreased renal function may be observed in patients with nail-patella syndrome. End-stage renal disease is relatively rare and is reported in approximately 5% of patients.

  • Preeclampsia: This condition is more common in patients with nail-patella syndrome than in the general population.

  • Ophthalmology: Ocular hypertension or open-angle glaucoma may be observed.

  • Neurology: Attention deficit disorder with and without hyperactivity (ADHD) may be more common in adults with nail-patella syndrome and does not exhibit the same increased male prevalence as in the general population. [14] Major depressive symptoms may also be part of the syndrome. A significant proportion of patients exhibit decreased sensitivity to pain and temperature in the extremities. Signs and symptoms of chronic fatigue may be present due to maldevelopment of the serotonergic system.

  • GI problems: Constipation and irritable bowel syndrome are more common in patients with nail-patella syndrome than in the general population.

A study by Bech et al found a Danish family in which early onset paroxysmal cranial dyskinesia was part of the nail-patella spectrum. The family had a novel variant in LMX1B, and the investigators suggested that the dyskinesia might be associated with aberrant dopaminergic circuits. [10]



Pes planus is seen in majority of patients with nail-patella syndrome. These patients also tend to have an overall typically thin body habitus, and they have difficulty gaining weight. Other findings on physical examination may include the following:

  • Nail/digit anomalies: Nails may be absent, hypoplastic, or dystrophic; triangular lunulae may be the sole nail anomaly. Typically, the thumb is most severely affected, with possible decreasing severity progressing to the fifth digit. Decreased creases over the distal interphalangeal (DIP) joints are noted.

  • Patellar anomalies: Patellae may be absent or hypoplastic. Dislocation in the superior and lateral direction is common. Pain is also common, and osteoarthritis may be present.

  • Iliac horns: These bony prominences are typically asymptomatic and may be palpable on the posterolateral iliac bones. If not palpable, they are often detected using radiography. They are present in about 70% of patients and are pathognomonic of nail-patella syndrome.

  • Elbow anomalies: Decreased flexion, supination, and pronation are noted. The radius may be hypoplastic and posteriorly placed. Skin webbing (pterygia) may be present.

  • Renal disease: Proteinuria with or without hematuria may be present in 30-50% of patients. This progresses to end-stage renal disease in approximately 5%. No evidence suggests that renal transplantation has different outcome in patients with nail-patella syndrome than in the general population.

  • Open-angle glaucoma: Optic nerve and visual field damage can be prevented with early detection of elevated intraocular pressure and appropriate treatment.

  • Lester sign: A hyperpigmented, irregular ring in the iris may be noted.



See the list below:

  • The LMX1B gene is a transcription factor involved in the dorsoventral patterning of vertebrate limbs (including patterning of the nails, digits, elbows and patellae), the differentiation and function of kidney podocytes, development of the anterior eye structures, and the CNS.

  • The loss of function of one allele of LMX1B is the only known cause of nail-patella syndrome. [8, 9, 10]