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Bilateral patellar hypoplasia: beyond the skeletal anomalies.

RADIOLOGIC DIAGNOSIS: Bilateral patellar hypoplasia with bilateral iliac horns consistent with Nail Patella Syndrome.


Nail patella syndrome (NPS), also known as Hereditary Osteo-Onychodysplasia or Fong's syndrome, is a rare autosomal dominant disorder with an incidence of 1 in 50,000 live births. (1) It was first described by Little (2,8) in 1897 as characterized by hypoplastic or absent patellae, dystrophic nails, elbow dysplasia, and iliac horns. For the past 50 years, great insight has been provided into the molecular origins of this syndrome.

This disorder is caused by heterozygous loss-of-function mutations in the LMX1B gene, which encodes transcription factors. (1) LMX1B is required for a wide range of developmental processes, including dorso-ventral patterning of the limbs, differentiation of dopaminergic and serotonergic neurons, patterning of the skull, development of the anterior segment of the eye, and the glomerular basement membrane (GBM). (1) Multiple organs can be affected, particularly the skeleton, nails, eyes, and kidneys. The degree to which each organ system is affected can vary significantly between individuals, even within the same family. (3) This disorder has complete penetrance but significant variation in its clinical expression.

Skeletal dysplasia is the major feature, and it is particularly evident in the knees, elbows, pelvis, spine, and feet. The most common findings are knee and elbow hypoplasia followed by the presence of iliac exostoses (horns). Knee and elbow manifestations have been associated with increased morbidity and manifested by recurrent subluxation and dislocation of the patellae and radial heads causing arthralgias and severe degenerative disease. The iliac horns are pathognomonic for NPS and can be palpable by physical examination, but they do not cause symptoms or gait disturbances. (3) Spine and foot anomalies, such as equinovarus and equinovalgus deformities, have been described but occur less frequently. (4) Nail dysplasia is an essential feature of this syndrome manifested by the presence of triangular lunulae that can be accompanied by anonychia, hemianonychia, nail hypoplasia, or longitudinal ridging. (4)

There are several disorders that have similar findings to those seen in patients with NPS. Different degrees of skeletal anomalies present with the following entities: Genitopatellar syndrome, Patella aplasia-hypoplasia syndrome, Meier-Gorlin syndrome, and Rapadilino syndrome.

In 1997, Lichter et al. (5) described the association of primary open angle glaucoma (POAG) in NPS patients, and it is considered a variable feature of this syndrome. In 40 to 50% of patients, the ectodermal element of the iris can be widened and hyperpigmented, causing a dark and irregular pupillary border known as Lester's sign. (9) Other possible anomalies include ocular hypertension and congenital cataracts. (4,5)

One of the most serious manifestations of NPS is kidney disease, which is present in up to 40% of patients with great variability in its incidence; it imposes the greatest impact on morbidity and mortality. (1,3) The involvement of renal disease in NPS patients was first associated in the 1950s. (7) In 2001, Morello et al. (8) elucidated the role of LMX1B in the pathway of normal GBM morphogenesis and renal dysplasia in NPS patients by demonstrating the dysregulation of type IV collagen expression. (8) Ultrastructural changes include collagen fibril deposition and hyaline thickening of the GBM. (7,8) Early manifestations include proteinuria and less frequently, hematuria. Most of the time, the course of this nephropathy is rather benign, and progression to end-stage renal disease (ESRD) is usually indolent, although cases of rapid progression have been described. (3,6)

The diagnosis of this entity is usually clinical, and radiology plays an important role for documenting the skeletal anomalies. Plain radiographs are the study of choice for initial diagnosis and continuous surveillance. Ultrasound and magnetic resonance can also be used. It is important to keep in mind the progression of ossification centers in children, since patellar anomalies can be missed. Family history is important, due to the inheritance pattern of this disease, and examination of all family members should be sought. Once the diagnosis has been established, patients should be referred for careful ophthalmologic examination, and annual screening should be performed for proteinuria and blood pressure control. DNA testing is currently available, but it is not necessary.

Orthopedic problems are usually treated conservatively with analgesics, physiotherapy, splinting, or bracing. Surgical treatment can be an option if deemed necessary, and magnetic resonance is an important study to perform for surgical planning. Hypertension and nephropathy are treated as in the general population. If nephropathy progresses to ESRD, reports of renal transplantation in individuals with NPS have been favorable. (3)

Our patient is currently being treated conservatively with analgesics and physiotherapy, showing no evidence of renal disease or ophthalmologic anomalies.


Special thanks to Dr. Enrique Palacios, section chief of Neuroradiology at Tulane University Health Sciences Center in New Orleans for his contributions to this publication.


(1.) Marini M, Bocciardi R, Gimelli S, Di Duca M, et al. A spectrum of LMX1B mutations in Nail-Patella syndrome: New point mutation, deletion, and evidence of mosaicism in unaffected parents. Genetics in Medicine 2010; 431-439.

(2.) Little EM. Congenital absence or delayed development of the patella. Lancet 1897; 3865:781-784.

(3.) Bongers EM, Gubler MC, Knoers NV. Nail-patella syndrome. Overview on clinical and molecular findings. Pediatr Nephrol 2002; 17:703-712.

(4.) Beals RK, Eckhardt AL. Hereditary onycho-osteodysplasia (Nail-Patella syndrome) A report of nine kindreds. J Bone Joint Surg Am 1969; 51: 505-16.

(5.) Lichter PR, Richards JE, Downs CA, Stringham HM, Boehnke M, Farley FA (1997) Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol 124:506-515.

(6.) Sweeney E, Fryer A, Mountford R, et al. Nail patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet 2003; 40: 153-62.

(7.) Hawkins CF, Smith OE (1950) Renal dysplasia in a family with multiple hereditary abnormalities including iliac horns. Lancet: 803-808.

(8.) Morello R, Zhou G, Dreyer SD, et al. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001 27:205-208.

(9.) Palacios E. Hereditary Osteo-Onycho-Dysplasia The Nail Patella Syndrome. Am J of Roentgenology, Radium Therapy and Nuclear Medicine 1987; 4:842-850.

Dr. Garza is a visiting Medical Doctor. Drs. Allen and Eghbalieh are second-year Radiology Residents at Tulane University Health Sciences Center in New Orleans. Dr. Neitzschman is a Professor of Radiology and the Chairman of the Department of Radiology at Tulane University Health Sciences Center in New Orleans, Louisiana. Dr. Serou is the Fellowship Program Director for musculoskeletal imaging at Tulane University Health Sciences Center in New Orleans.
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Title Annotation:Radiology Case of the Month
Author:Allen, Laveil; Eghbalieh, Navid; Patel, Montu; Garza, Lorena; Neitzschman, Harold R.; Serou, Michael
Publication:The Journal of the Louisiana State Medical Society
Article Type:Clinical report
Geographic Code:1USA
Date:Mar 1, 2013
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