Ophthalmological Aspects of Pierson Syndrome

doi:10.1016/j.ajo.2008.05.039

American Journal of Ophthalmology

Volume 146, Issue 4, October 2008, Pages 602-611.e1

https://doi.org/10.1016/j.ajo.2008.05.039 Get rights and content

Purpose

To study the ocular phenotype of Pierson syndrome and to increase awareness among ophthalmologists of the diagnostic features of this condition.

Design

Retrospective, observational case series.

Methods

A multicenter study of 17 patients with molecularly confirmed Pierson syndrome. The eye findings were reviewed and compared to pertinent findings from the literature.

Results

The most characteristic ocular anomaly was microcoria. A wide range of additional abnormalities were found, including posterior embryotoxon, megalocornea, iris hypoplasia, cataract, abnormal lens shape, posterior lenticonus, persistent fetal vasculature, retinal detachment, variable axial lengths, and glaucoma. There was high interocular and intrafamilial variability.

Conclusions

Loss-of-function mutations in laminin β2 (LAMB2) cause a broad range of ocular pathology, emphasizing the importance of laminin β2 in eye development. Patients with Pierson syndrome can initially present with ocular signs alone. In newborns with marked bilateral microcoria, Pierson syndrome should be considered and renal function investigated.

Section snippets

Methods

This is a retrospective review of the detailed ophthalmologic findings in 17 patients from 16 families. All patients had molecularly confirmed Pierson syndrome. Two patients (Patients 11 and 13) each had an affected sibling excluded from the study, as only limited data were available. Four patients (Patients 4, 6, 7, and 16) have previously been published.3, 8, 9, 10, 11 In one patient (Patient 12), an iris biopsy was obtained during pupilloplasty. This specimen was fixed in 10% formalin,

Results

The major systemic findings for all patients (nine males; eight females) are summarized in Table 1 and the ophthalmologic data is presented in Table 2 and illustrated in Figure 1, with the histopathology in Figure 2.

Discussion

We present the ophthalmic manifestations of 17 patients with Pierson syndrome and review the eye findings in previously reported patients with LAMB2 mutations. As the main focus of previous reports has been the renal and/or genetic manifestations of the disorder, the ophthalmic data in these reports were often incomplete. This hampers comparison with our findings. However, our data confirm widespread involvement of the eye in Pierson syndrome and expand upon the previously reported phenotype.

Cecilie Bredrup, MD, is a graduate of the Faculty of Medicine, University of Bergen, Bergen, Norway, in 1999. She completed residency training at Haukeland University Hospital, Bergen, Norway and a fellowship in Pediatric Ophthalmology at Great Ormond Street Hospital for Children in 2006. Dr Bredrup is currently working in a combined position as a fellow at Haukeland University Hospital and a PhD student at University of Bergen. Dr Bredrup's research interests include pediatric ophthalmology,

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Cited by (60)

Early-Onset Myopia and Retinal Detachment without Typical Microcoria or Severe Proteinuria due to a Novel LAMB2 Variant
2024, Ophthalmology Retina
To describe the ocular and renal features, as well as outcomes of retinal detachment repair, in patients with a novel, homozygous laminin β-2 (LAMB2) pathogenic variant.
Single-center retrospective chart review of patients with a homozygous variant, c.619T>C p.(Ser207Pro), in the LAMB2 gene.
Eleven patients (22 eyes) from 4 families.
Demographic data and ocular findings were recorded. Patients were recalled for a detailed renal evaluation.
Ocular features, renal features, and outcomes of retinal detachment repair.
The mean age at presentation was 6.0 (range, 1–26) years. None of the study eyes had microcoria, and none of the patients had nephrotic-range proteinuria. The mean refraction and axial length were −7.9 diopters (range, −4.0 to −12.0 diopters) and 25.3 (range, 22.7–27.7) mm, respectively. Eleven eyes (50%) had cataract at presentation. Fifteen eyes had a clear view to the fundus and all showed tessellated myopic fundus, avascular peripheral retina evident clinically or on fluorescein angiography, and rudimentary fovea. Optic disc pallor was observed in 10 eyes (66.7%). Straightened retinal vessels, abnormal vascular emanation (situs inversus) from the optic disc, supernumerary vascular branching at the optic disc, and vascular tortuosity were observed in 10 (66.7%), 2 (13.4%), 2 (13.4%), and 2 (13.4%) eyes, respectively. Discrete areas of punched-out chorioretinal atrophy were observed in 4 (26.7%) eyes. Spectral-domain OCT showed retinal and choroidal thinning in 13 eyes (86.7%), retinoschisis temporal to the fovea in 2 eyes (13.4%), and rudimentary fovea in 15 eyes (100%). Among the 22 eyes, 14 eyes (63.6%) developed rhegmatogenous retinal detachment (RRD), mostly during childhood, of which 5 patients had bilateral RRD. Eight eyes were operated on and 6 (75%) achieved retinal reattachment at the last follow-up. The mean preoperative visual acuity was 20/300 and the mean postoperative visual acuity at the last follow-up was 20/400.
This study describes a distinct phenotype of LAMB2-related disease with a novel, homozygous LAMB2 variant, and further expands the spectrum of ophthalmic and renal features, and the molecular genetic basis, of LAMB2-related disease. Because the typical microcoria and nephrotic-range proteinuria might be absent, the retinal features can guide the diagnosis.
The authors have no proprietary or commercial interest in any materials discussed in this article.
Systematic Review of Clinical Characteristics and Genotype-Phenotype Correlation in LAMB2-Associated Disease
2023, Kidney International Reports
Laminin subunit beta-2 (LAMB2)-associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms. In recent years, however, the widespread use of next-generation sequencing (NGS) has helped to discover a variety of phenotypes associated with this disease. Therefore, we conducted this systematic review.
A literature search of patients with LAMB2 variants was conducted, and 110 patients were investigated, including 12 of our patients. For genotype-phenotype correlation analyses, the extracted data were investigated for pathogenic variant types, the severity of nephropathy, and extrarenal symptoms. Survival analyses were also performed for the onset age of end-stage kidney disease (ESKD).
Among all patients, 81 (78%) presented with congenital nephrotic syndrome, and 52 (55%) developed ESKD within 12 months. The median age at ESKD onset was 6.0 months. Kidney survival analysis showed that patients with biallelic truncating variants had a significantly earlier progression to ESKD than those with other variants (median age 1.2 months vs. 60.0 months, P < 0.05). Although the laminin N-terminal domain is functionally important in laminin proteins, and variants in the laminin N-terminal domain are said to result in a severe kidney phenotype such as earlier onset age and worse prognosis, there were no significant differences in onset age of nephropathy and progression to ESKD between patients with nontruncating variants located in the laminin N-terminal domain and those with variants located outside this domain.
This study revealed a diversity of LAMB2-associated diseases, characteristics of LAMB2 nephropathy, and genotype-phenotype correlations.
Pierson Syndrome in an Infant With Congenital Nephrotic Syndrome and Unique Brain Pathology
2020, Kidney International Reports
Citation Excerpt :
Unlike renal involvement, the ocular changes associated with LAMB2 mutations are variable and in some cases may be noted before the onset of renal dysfunction. Microcoria, which is defined as a pupillary diameter < 2 mm, is the most well-described ocular manifestation of Pierson syndrome, whereas other findings such as iris abnormalities, glaucoma, cataracts, and retinal changes have also been noted.6 Other extrarenal manifestations of LAMB2 mutations have additionally been reported, predominantly in patients with less severe mutations who survive infancy, and include neurodevelopmental deficits with delayed motor and cognitive development, hypotonia,8 hearing deficits,9 and bone and skeletal changes.S3
Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene
2018, Journal of AAPOS
Citation Excerpt :
The abnormal clinical findings in our case were microcoria, flat iris, iris processes, cataract, retinal degeneration, and high myopia. These findings have been reported in previous cases, but there are some abnormalities that we did not observe in our patient, for example, megacornea, retinal detachment, and persistent fetal vasculature.6 There is no consensus on which phenotype is due to which mutation, because the syndrome is very rare.
Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities. The ocular findings in Pierson syndrome are not well understood, because the incidence of this syndrome is very rare. We report ocular findings in a 5-month-old boy with Pierson syndrome with a novel mutation in LAMB2. We performed a pupilloplasty for his microcoria. Ophthalmic examinations after surgery revealed that he had cataract, severe retinal degeneration, and high myopia. Optical coherence tomography showed the collapse of retinal layer structures and a marked decrease of choroidal thickness. Immunohistochemistry and electron microscopy examinations revealed abnormal iris differentiation and thinning or defect of basal membranes. These results suggest that the development of the iris, lens, retina, and choroid are affected in this type of mutation.
Ocular manifestations of the genetic causes of focal and segmental glomerulosclerosis
2024, Pediatric Nephrology
Multidisciplinary and multidimensional approaches to transplantation in children with rare genetic kidney diseases
2023, Pediatric Transplantation

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Original articleOphthalmological Aspects of Pierson Syndrome

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Kidney Int

An unusual congenital and familial congenital malformative combination involving the eye and kidney

J Genet Hum

Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome

Am J Med Genet A

Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities

Hum Mol Genet

Familial infantile nephrotic syndrome with ocular abnormalities

Pediatr Nephrol

A syndrome of immune complex glomerulonephritis and ophthalmic abnormalities

J Med Genet

A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2

Nephrol Dial Transplant

Neurodevelopmental deficits in Pierson (microcoria-congenital nephrosis) syndrome

Am J Med Genet A

A case of atypical congenital nephrotic syndrome

Pediatr Nephrol

LAMB2 gene mutation as a cause of congenital nephrotic syndrome with distinct eye abnormalities and hypotonia

Przegl Lek

Original article
Ophthalmological Aspects of Pierson Syndrome