From the Department of Pediatrics (TS), Tripler Army Medical Center; the Department of Pediatrics (DY, LS), Kapiolani Medical Specialists (LS); and the Division of Neonatology (SL), Department of Pediatrics, and the Department of Surgery (JD), John A. Burns School of Medicine, Honolulu, Hawaii.
The authors have no financial or proprietary interest in the materials presented herein.
The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
Address correspondence to Taylor Sawyer, DO, Department of Pediatrics, Tripler Army Medical Center, MCHK-PE, 1 Jarrett White Road, Honolulu, HI 96859.
Pierson syndrome is a recently described autosomal recessive genetic disorder resulting from mutations in the LAMB2 gene that lead to loss of β-2 laminin expression.1,2 β-2 laminin is one of a group of laminin proteins found in the basement membrane of various parts of the body, including the kidney, lung, skin, nervous system, and eye. Within the eye, laminins can be found in the cornea, lens, ciliary body, and retina.3 Pierson syndrome typically presents in the neonatal period with bilateral microcoria (nonreactive severe miosis) and congenital nephrotic syndrome. Associated with the clinical finding of microcoria is a complex array of developmental ocular malformations, including hypoplasia of the iris and ciliary body, hypoplasia of the ciliary and papillary muscles, lens malformations, and lenticonus posterior, corneal, and retinal anomalies.1 In addition to the eye and renal pathology, severe neurodevelopmental deficits are also seen.4 To date, approximately 25 cases of Pierson syndrome have been reported worldwide, with only 1 reported case in the United States.2,5 This report describes a case of Pierson syndrome, with an emphasis on the ocular findings.
A full-term female infant was transferred to the authors’ institution at 5 days of age for renal failure and severe bilateral miosis that had persisted since birth. Ophthalmologic examination showed response to light in both eyes with blinking of each eye. The pupils were miotic, pinpoint, and nonreactive (Fig. 1). The pupils did not dilate with cyclopentolate (Cyclomydril; Alcon Laboratories, Fort Worth, TX) drops. Proptosis was noted bilaterally. Intraocular pressure was 17 mm Hg in both eyes with a tonometer (Tono-Pen; Reichert, Depew, NY). There was no strabismus. Portable slit-lamp examination showed normal eyelids, eyelashes, and conjunctivae. The corneas were clear with shallow anterior chambers. Hypoplastic irides with radial iris vessels were noted. The lens was completely opacified in each eye. The corneas measured approximately 9 mm in diameter in both eyes. Fundus examination was not possible because the patient had cataracts in both eyes.
Figure 1. Clinical Finding of Bilateral Microcoria, Consistent with Pierson Syndrome.
Magnetic resonance imaging of the eyes showed symmetric large globes and posterior segment abnormalities in the left eye and possibly the right eye, suggestive of retinal detachment. A peripheral patchy bright T2 signal was seen within the vitreous humor of the left eye. B-scan showed enlarged globes, increased thickening of the choroidal scleral complex in the posterior fundus, and the appearance of stalks arising from the optic nerve and extending to the anterior vitreous (Fig. 2). Increased debris was also seen in the anterior retinal pars plana area temporally. The stalks in both eyes were noted to fall out with decreasing sensitivity and thus were not believed to represent retinal detachment. No ocular surgery was performed.
Figure 2. Retinal B-Scan Image Showing a Stalk Arising from the Optic Nerve and Extending into the Anterior Vitreous.
Additional clinical evaluation included multiple laboratory and imaging studies evaluating for inborn errors of metabolism and toxoplasmosis, rubella, cytomegalovirus, and herpes simplex infection, and all findings were negative. Consultations were obtained from the genetics, infectious disease, cardiology, neurology, and nephrology departments. The patient was diagnosed as having congenital nephrotic syndrome and subsequently had anuria requiring peritoneal dialysis. Renal biopsy showed abnormalities of the basement membrane consistent with Pierson syndrome.1,2 The patient also exhibited severe neurodevelopmental deficits consistent with other reported cases.4 Genetic testing for Pierson syndrome confirmed a mutation of the LAMB2 gene inherited from the mother, but was unable to identify the paternally transmitted allele. This was likely due to novel mutation in the paternal LAMB2 gene that could not be detected by current assays.
This patient represents the second reported case of Pierson syndrome in the United States. Ocular findings in this case that are consistent with Pierson syndrome include the pathognomonic findings of bilateral microcoria combined with anterior and posterior segment dysgenesis.2 Unique eye findings in this case are the stalks arising from both optic nerves on retinal B-scan in the setting of enlarged globes with normal intraocular pressure. These stalks were believed to be the result of hyperplastic primary vitreous. To the authors’ knowledge, this finding of enlargement of the globes with hyperplastic primary vitreous has not been reported previously in Pierson syndrome.
Laminins are the major noncollagenous component of basement membranes.6 They are heterotrimeric extracellular matrix glycoproteins composed of one alpha, one beta, and one gamma chain.6 Laminins are vital for the assembly of basement membranes and interact with collagen and other extracellular matrix molecules.6 The eye and renal pathology in Pierson syndrome results from deficient or absent β-2 laminin expression caused by inherited mutations in the LAMB2 gene.1,2 β-2 laminin has been detected in the basement membrane of various parts of the eye, including the inner nuclear layer, the internal limiting membrane, the retina, and the lens capsule.6 Deficient or absent production of β-2 laminin results in dysgenesis of both the anterior and posterior eye segments. Lack of β-2 laminin in the glomerular basement membrane results in nephrotic syndrome and renal failure.1,2 It is assumed that the lack of β-2 laminin in the central nervous system and at the neuromuscular junction accounts for the neurodevelopmental deficiencies seen in Pierson syndrome.4
In clinical practice, bilateral microcoria is extremely rare. An Online Mendelian Inheritance in Man (OMIM) search for microcoria showed only two hits other than Pierson syndrome (OMIM 609049), including congenital microcoria (OMIM 156600) and polycystic kidney, cataract, and congenital blindness (OMIM 263100). Congenital microcoria is an autosomal dominant syndrome consisting of isolated hypoplasia of the dilator muscle of the iris. The occurrence of polycystic kidney, cataract, and congenital blindness constitutes a syndrome reported in 1963 by Fairley et al.,7 who described three siblings with optic atrophy, retinal changes, and nystamus. Either of these syndromes may present with microcoria, but neither presents with the associated nephrotic syndrome seen in Pierson syndrome.
The diagnosis of Pierson syndrome can be made with reasonable certainty based on the clinical findings of microcoria in combination with congenital nephrotic syndrome in the same patient. Thus, any patient presenting with microcoria should be screened for renal dysfunction with routine urinalysis and serum blood urea nitrogen and creatinine levels to exclude Pierson syndrome. Conversely, any infant presenting with congenital nephrotic syndrome should undergo careful ophthalmologic examination looking for findings consistent with Pierson syndrome.1,2 Early diagnosis of Pierson syndrome and knowledge of its expected neurodevelopmental sequelae may assist with family counseling and surgical planning in these patients.4
- Zenker M, Aigner T, Wendler O, et al. Human laminin β-2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet. 2004;13:2625–2632. doi:10.1093/hmg/ddh284 [CrossRef]
- Zenker M, Tralau T, Lennert T, et al. Congenital nephrosis, mesangial sclerosis and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. Am J Med Genet. 2004;130:138–145. doi:10.1002/ajmg.a.30310 [CrossRef]
- Kohno T, Sorgente N, Ishibashi T, et al. Immunofluorescent studies of fibronectin and laminin in the human eye. Invest Ophthalmol Vis Sci. 1987;28:506–514.
- Wuhl E, Kogan J, Zurowska A, et al. Neurodevelopmental deficiencies in Pierson (microcoria-congenital nephrosis) syndrome. Am J Med Genet A. 2007;143:311–319.
- VanDeVoorde R, Witte D, Kogan J, Goebel J. Pierson syndrome: a novel cause of congenital nephrotic syndrome. Pediatrics. 2006;118:e501–e505. doi:10.1542/peds.2005-3154 [CrossRef]
- Bystrom B, Virtanen I, Rousselle P, et al. Distribution of laminins in the developing human eye. Invest Ophthalmol Vis Sci. 2006;47:777–785. doi:10.1167/iovs.05-0367 [CrossRef]
- Fairley K, Leighton P, Kincaid-Smith P. Familial visual defects associated with polycystic kidney and medullary sponge kidney. Br Med J. 1963;1:1060–1063. doi:10.1136/bmj.1.5337.1060 [CrossRef]