Nail-Patella Syndrome Clinical Presentation

Updated: Sep 20, 2022
  • Author: Anna Choczaj-Kukula, MD, PhD; Chief Editor: Dirk M Elston, MD  more...
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Physical Examination

Nail dysplasia and patellar hypoplasia are essential findings for diagnosis of nail-patella syndrome (NPS). Other diagnostic features are hypoplasia of the radial head and iliac prominences, which are known as iliac horns. [60, 61] Renal complications and ophthalmologic problems can accompany NPS. [62, 63]  It is important to examine the nails in children with skeletal dysplasias so a diagnosis of NPS is not missed. [20]


Nail changes are present in 98% of individuals with NPS and may be present since birth. [7, 11] Patients have different degrees of nail dysplasia, with almost all patients having bilateral and symmetric nail changes. [64, 65] The nails, especially those on the thumbs, are typically absent, may be hypoplastic, discolored, and separated by a cleft. Nail dysplasia, a typical feature, is more severe on the ulnar side than on the radial side, with the thumb most severely affected and improvement toward the fifth digit. [66, 65] The toenails are rarely involved; if dysplasia is present, it most frequently affects the little toenail. [7, 65, 67, 67]

Other nail abnormalities in patients with NPS include splitting, longitudinal crease, longitudinal fracture, pseudopterygium, longitudinal or horizontal ridging, pitting, koilonychia, poor lunula formation, and discoloration. [68, 69, 70]

In the absence of other nail changes, V-shaped triangular lunulae with a distal peak in the midline are pathognomonic for NPS. [71, 72] The presence of triangular lunulae has been suggested to be a good marker of medial nail damage (longitudinal crease, longitudinal fracture, and pseudo-pterygium). [69]

Bones and joints

Complaints related to the knee are reported in up to 74% of cases, [73] with symptoms of instability, pain, or a combination of both. [74] Patellar involvement is present in approximately 90% of patients; however, patellar aplasia occurs in only 20%. Isolated unilateral absent patella and contralateral small patella have been reported. [75] In instances in which the patellae are smaller or luxated, the knees may be unstable. Synovial band preventing the engagement of the patella into the trochlear groove has been described. [76]

The elbows may have limited motion (eg. limited pronation, supination, extension). Subluxation of the radial head may occur. Pterygia (webbing) may be present across the elbow. Arthrodysplasia of the elbows is reported in approximately 90% of patients. [32, 77]

General hyperextension of the joints can be present.

Exostoses arising from the posterior aspect of the iliac bones are present in as many as 80% of patients; this finding is considered pathognomonic for the syndrome [13] and can be observed by ultrasound scanning from the third trimester of pregnancy. [78] Iliac horns may be also seen on radiographs at birth, and by bone scan. [61]

Other reported bone changes include scoliosis, scapular hypoplasia, genu valgum, club feet, and the presence of cervical ribs. [79]

Kidneys  [80, 81]

From 22-60% patients present with renal anomalies, which may result in only asymptomatic proteinuria. [82] Hematuria; nephrotic syndrome, [83, 84] which may develop prior to orthopedic symptoms [85] ; and progression to renal failure requiring dialysis or transplantation have been observed in approximately 10% of patients. [51, 10] NPS patients are often affected by glomerulonephritis. [86]

Pedal edema [87] and recurrent urinary tract infections can also be manifestations of renal involvement.

Isolated nephropathy cases without nail, patellar, or skeletal abnormality, caused by some mutations in the homeodomain of LMX1B, have been reported. [88, 89, 90, 91]


Ocular manifestations may include variable degrees of intraocular hypertension, glaucoma, or normal tension glaucoma. [92, 93]

Hyperpigmentation of the pupillary margin of the iris, the Lester iris, occurs in 45% of patients with NPS. This can be a helpful diagnostic sign.

Other abnormalities, such as heterochromia of the iris with cloverleaf deformity, cataracts, microcornea, and glaucoma, have also been reported. [94]


Skin laxity may be present. Webbing of the elbows and absent skin creases in the distal parts of the fingers are described in some patients. [95] A case of coexisting ectopic cilia and NPS in one patient has been described. [96]

Dysmorphic facial features have been described in children with NPS. A high forehead hairline, especially on the temples, may be seen in women.

One third of NPS patients have gastrointestinal involvement—constipation or irritable bowel syndrome. [13, 97]

Some studies suggest that NPS phenotype may be more extensive than previously recognized, including neurologic and neurobehavioral aspects. Patients with NPS are at increased risk of attention deficit-hyperactivity disorder (ADHD) and depressive disorder, which have been attributed to the LMX1B protein dysfunctions in the development of mesoencephalic dopaminergic signalling and the serotoninergic signalling system. [98]

Schizophrenia was reported in patients with NPS. Based on LMX1B expression in brain regions that are implicated in neuropsychiatric illness, and especially in the development of dopaminergic neurons, it has been hypothesized that schizophrenia may be part of the clinical spectrum of NPS. [99, 100]

Possible neurologic symptoms include diminished pain and temperature response, numbness, tingling, and burning sensation in hands and feet. [14]

A case of a child with NPS and a short stature and hypothyroidism has been reported. [101]