-
American Journal of Ophthalmology Oct 2008To study the ocular phenotype of Pierson syndrome and to increase awareness among ophthalmologists of the diagnostic features of this condition.
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 beta2 (LAMB2) cause a broad range of ocular pathology, emphasizing the importance of laminin beta2 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.
Topics: Abnormalities, Multiple; Eye Abnormalities; Female; Humans; Infant, Newborn; Iris; Laminin; Male; Mutation, Missense; Nephrotic Syndrome; Phenotype; Pupil Disorders; Retrospective Studies; Syndrome
PubMed: 18672223
DOI: 10.1016/j.ajo.2008.05.039 -
Kidney International Reports Dec 2020
PubMed: 33305134
DOI: 10.1016/j.ekir.2020.09.023 -
Kidney360 Dec 2021
Topics: Collagen Type IV; Female; Humans; Laminin; Male; Nephritis, Hereditary
PubMed: 35419542
DOI: 10.34067/KID.0007312021 -
Bone Jan 2018Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS)...
INTRODUCTION
Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described.
METHODS
We report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty. This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50mL/min per 1.73m), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of "normal low" quantity and quality; major radial and cubital deformations were observed. Stainings of laminin β2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin β2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone.
CONCLUSION
This is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3β1, receptor for laminin β2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin β2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin β2 in bone physiology.
Topics: Abnormalities, Multiple; Adolescent; Eye Abnormalities; Female; Humans; Laminin; Mutation; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Neuromuscular Diseases; Pupil Disorders
PubMed: 29051055
DOI: 10.1016/j.bone.2017.10.015 -
Ophthalmic Genetics Jun 2021: To report a patient with Pierson syndrome who presented with neovascular glaucoma (NVG) after cataract surgery.: Retrospective case report.: A 17-year old monocular...
: To report a patient with Pierson syndrome who presented with neovascular glaucoma (NVG) after cataract surgery.: Retrospective case report.: A 17-year old monocular female presented with sudden onset of pain and decreased vision in the right eye. On examination, she had intraocular pressure (IOP) of 50 mmHg, aggressive iris neovascularization (NVI) and 3-piece IOL. Fundus examination revealed pale disc with tessellated fundus and parapapillary atrophy. Vascular arcades were vertically stretched with avascular ischemic retina starting from the near periphery. Macula appeared thin and atrophic. An intravitreal injection of 0.05 mg/0.1 ml bevacizumab was given to the right eye followed by Ahmed glaucoma valve (AGV) implantation. Assessment of her brother revealed similar posterior segment changes. A subsequent urine analysis showed proteinuria and high albumin to creatinine ratio. Next-generation sequencing for gene revealed a homozygous c.4573 + 1 G > A variant confirming the diagnosis of Pierson syndrome.: This case expands our knowledge on retinal ischemia in the setting of Pierson syndrome. Close monitoring after intraocular surgery is recommended to look for the development of NVG.
Topics: Adolescent; Angiogenesis Inhibitors; Bevacizumab; Combined Modality Therapy; Female; Glaucoma Drainage Implants; Glaucoma, Neovascular; High-Throughput Nucleotide Sequencing; Humans; Intraocular Pressure; Laminin; Lens Implantation, Intraocular; Male; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Phacoemulsification; Pupil Disorders; Retrospective Studies; Siblings; Tonometry, Ocular; Young Adult
PubMed: 33554690
DOI: 10.1080/13816810.2021.1881982 -
Pediatric Transplantation Dec 2017Congenital nephrotic syndrome is commonly associated with mutations in genes that encode podocyte and slit diaphragm proteins or the structural and regulatory proteins...
Congenital nephrotic syndrome is commonly associated with mutations in genes that encode podocyte and slit diaphragm proteins or the structural and regulatory proteins of the GBM. These mutations lead to the formation of dysfunctional proteins, which account for the resistance of the renal manifestations to conventional treatment methods. Consequently, patients become renal replacement therapy dependent. Mutation of the LAMB2 gene is associated with Pierson syndrome, which is an autosomal recessive disorder characterized by congenital nephrotic syndrome and ocular abnormalities. In this report, a 2-year-old male patient who was diagnosed with Pierson syndrome is presented. He had bilateral microcoria and developmental delay in addition to nephrotic syndrome. His renal function deteriorated rapidly, and he underwent a deceased donor kidney transplantation. He showed dramatic improvement after kidney transplantation; in addition to having good renal function, he started to catch up to his peers in terms of growth. Pierson syndrome should be considered during the diagnostic investigations of children with renal manifestations and ocular abnormalities. Children with Pierson syndrome must be evaluated in terms of kidney transplantation as soon as they are diagnosed.
Topics: Abnormalities, Multiple; Child, Preschool; Eye Abnormalities; Humans; Kidney Transplantation; Male; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders
PubMed: 29094445
DOI: 10.1111/petr.13076 -
Pediatrics Aug 2006In this report, we describe a newborn infant who presented with congenital nephrotic syndrome and renal insufficiency, as well as bilateral microcoria. This...
In this report, we describe a newborn infant who presented with congenital nephrotic syndrome and renal insufficiency, as well as bilateral microcoria. This constellation of findings is a hallmark of Pierson syndrome, a newly recognized genetic disorder that is caused by a deficiency of beta2 laminin in the basement membrane. Our patient demonstrated classic histopathologic findings of Pierson syndrome on renal biopsy, including absence of beta2 laminin on immunofluorescent staining, and genetic testing confirmed the diagnosis. We conclude that Pierson syndrome should be included in the differential diagnosis for congenital nephrotic syndrome, especially in patients with ocular abnormalities.
Topics: Adult; Basement Membrane; Biopsy; Diagnosis, Differential; Edema; Female; Heterozygote; Humans; Hypertension, Renal; Infant, Newborn; Infant, Small for Gestational Age; Kidney; Kidney Glomerulus; Laminin; Male; Mesangial Cells; Miosis; Nephrotic Syndrome; Oligohydramnios; Pregnancy; Syndrome; Ultrasonography, Prenatal
PubMed: 16864643
DOI: 10.1542/peds.2005-3154 -
Pediatric Nephrology (Berlin, Germany) May 2012Pierson syndrome, caused by mutations in the LAMB2 gene, was originally described as a combination of microcoria and congenital nephrotic syndrome, rapidly progressing...
BACKGROUND
Pierson syndrome, caused by mutations in the LAMB2 gene, was originally described as a combination of microcoria and congenital nephrotic syndrome, rapidly progressing to end-stage renal failure.
CASE-DIAGNOSIS/TREATMENT
We report a minor variant of Pierson syndrome in a teenage girl with severe myopia since early infancy and proteinuria first detected at age 6. At the age of 11 she was found to carry a unique homozygous non-truncating LAMB2 mutation in exon 2: c.T240G (p.S80R). Renal biopsy revealed mild diffuse mesangial sclerosis and residual expression of laminin β2. Today at age 14, on treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, she continues to have nephrotic range proteinuria, but a normal glomerular filtration rate.
CONCLUSIONS
LAMB2 mutations should be considered in all patients with glomerular proteinuria and abnormal ocular phenotype, irrespective of age and disease severity.
Topics: Abnormalities, Multiple; Adolescent; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Eye Abnormalities; Female; Glomerular Filtration Rate; Humans; Kidney; Laminin; Losartan; Mutation; Mutation, Missense; Myasthenic Syndromes, Congenital; Myopia; Nephrotic Syndrome; Phenotype; Proteinuria; Pupil Disorders; Ramipril; Retinal Detachment; Vision Disorders
PubMed: 22228401
DOI: 10.1007/s00467-011-2088-2 -
Pediatric Nephrology (Berlin, Germany) Nov 2021Genetic studies of hereditary nephrotic syndrome (NS) have identified more than 50 genes that, if mutated, are responsible for monogenic forms of steroid-resistant NS... (Review)
Review
Genetic studies of hereditary nephrotic syndrome (NS) have identified more than 50 genes that, if mutated, are responsible for monogenic forms of steroid-resistant NS (SRNS), either isolated or syndromic. Most of these genes encode proteins expressed in the podocyte with various functions such as transcription factors, mitochondrial proteins, or enzymes, but mainly structural proteins of the slit diaphragm (SD) as well as cytoskeletal binding and regulator proteins. Syndromic NS is sometimes associated with neurological features. Over recent decades, various studies have established links between the physiology of podocytes and neurons, both morphologically (slit diaphragm and synapse) and functionally (signaling platforms). Variants in genes expressed in different compartments of the podocyte and neurons are responsible for phenotypes associating kidney lesions with proteinuria (mainly Focal and Segmental Glomerulosclerosis (FSGS) or Diffuse Mesangial Sclerosis (DMS)) and central and/or peripheral neurological disorders. The Galloway-Mowat syndrome (GAMOS, OMIM#251300) associates neurological defects, microcephaly, and proteinuria and is caused by variants in genes encoding proteins of various functions (microtubule cytoskeleton regulation (WDR73), regulation of protein synthesis via transfer RNAs (KEOPS and WDR4 complexes)). Pierson syndrome (OMIM#609049) associating congenital nephrotic syndrome and central neurological and ophthalmological anomalies is secondary to variants in LAMB2, involved in glomerular and ocular basement membranes. Finally, Charcot-Marie-Tooth-FSGS (OMIM#614455) combines peripheral sensory-motor neuropathy and proteinuria and arises from INF2 variants, resulting in cytoskeletal polymerization defects. This review focuses on genetic syndromes associating nephrotic range proteinuria and neurological involvement and provides the latest advances in the description of these neuro-renal disorders.
Topics: Humans; Nephrotic Syndrome; Proteinuria
PubMed: 33791874
DOI: 10.1007/s00467-020-04903-x -
Pediatric Nephrology (Berlin, Germany) Jun 2008Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes the laminin beta2 chain, and is clinically characterized by congenital nephrotic syndrome (CNS)...
Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes the laminin beta2 chain, and is clinically characterized by congenital nephrotic syndrome (CNS) and bilateral microcoria. Here, we describe two cases of Pierson syndrome involving atypical phenotypes. Patient 1 presented with congenital microcoria and infantile nephrotic syndrome. Despite persistent nephrotic syndrome, her renal function was maintained normally until she was 6 years old. Genetic analysis revealed two frame-shifting deletions (truncating mutations) in the LAMB2 gene. Patient 2 presented with isolated CNS without ocular involvement. Her renal function deteriorated progressively over several months, and retinal detachment in the right eye developed when she was aged 10 months. LAMB2 analysis revealed a missense mutation in one allele and a frame-shifting deletion in the other allele. Electron microscopy of a renal biopsy revealed irregular lamellation of the glomerular basement membrane (GBM) in both patients. The phenotypes of Pierson syndrome vary widely, and the severity of the renal phenotype is not always parallel to that of the ocular phenotype. The phenotypic variability likely reflects genotype-phenotype correlations, but unknown genetic or environmental modifiers may play an additional role. Ultrastructural changes of the GBM are a useful diagnostic indicator.
Topics: DNA Mutational Analysis; Eye Abnormalities; Female; Genetic Predisposition to Disease; Glomerular Basement Membrane; Humans; Infant; Infant, Newborn; Kidney; Kidney Function Tests; Korea; Laminin; Mutation; Nephrotic Syndrome; Phenotype; Severity of Illness Index; Ultrasonography
PubMed: 18278520
DOI: 10.1007/s00467-008-0748-7