APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: LAMB2

Microcoria-congenital nephrotic syndrome

Microcoria
Nephrotic syndrome
Pigmentary retinopathy
Kidney failure
Psychomotor retardation
Cataracts
Retinal detachment
Muscle weakness
Optic atrophy
Glaucoma

Pierson Syndrome

Clinical Characteristics

General description (for patients):   

This is a disorder present at birth. It is characterized by eye abnormalities and severe, progressive kidney disease. The pupils of the eye are usually very small and do not dilate well. The retina in the back of the eye is also abnormal and prone to detachments. Cataracts and glaucoma are sometimes seen. The kidney disease often progresses to failure in the first decade of life. Many infants are floppy with poor muscle tone and may have some degree of mental retardation, never achieving the usual sitting and walking milestones. 

Medical description:

This is a congenital syndrome of neurologic, renal, and eye disease. Kidney disease from birth leads to the nephrotic syndrome and eventual kidney failure even within a few months of birth but sometimes not until adulthood. Hypoalbuminemia, proteinuria and hypertension are common. Severe psychomotor retardation is common and many infants never achieve normal milestones.  The pupils are abnormally small and do not dilate. The retina has a pigmentary retinopathy and is prone to spontaneous detachments. Cataracts and glaucoma occur in about one-fourth of patients. The corneas may appear large, even suggesting the buphthalmic appearance seen in congenital glaucoma. Optic atrophy and severe visual impairment are present in many patients. There is considerable interocular, interfamilial and even intrafamilial variation in these signs.

Genetics:

This is an autosomal recessive disorder due to mutations in the LAMB2 gene on chromosome 3. It has so far been described only in the Old Order Mennonites of Eastern Pennsylvania.

Treatment:

Kidney transplants, cataract surgery and repair of retinal detachments may be done but careful patient selection is necessary because of the poor general prognosis and the neurological deficits.

Prognosis:

This disorder carries a poor prognosis for life although a few have lived to adulthood. Many infants die in the first decade of life. The visual prognosis is likewise poor. 

Ancillary treatments and support:

There is no treatment known for the basic disease. Lifelong monitoring is necessary. Systemic hypertension and glaucoma can be treated. 

Specialists and specialty centers:

Ophthalmologists, pediatricians, and nephrologists generally make the diagnosis and provide consultation.

References:

Bredrup C, Matejas V, Barrow M, Bláhová K, Bockenhauer D, Fowler DJ, Gregson RM, Maruniak-Chudek I, Medeira A, Mendonça EL, Kagan M, Koenig J, Krastel H, Kroes HY, Saggar A, Sawyer T, Schittkowski M, SwietliƄski J, Thompson D, VanDeVoorde RG, Wittebol-Post D, Woodruff G, Zurowska A, Hennekam RC, Zenker M, Russell-Eggitt I. Ophthalmological aspects of Pierson syndrome. Am J Ophthalmol. 2008 Oct;146(4):602-611. PubMed PMID: 18672223.

Zenker M, Tralau T, Lennert T, Pitz S, Mark K, Madlon H, Dötsch J, Reis A, Müntefering H, Neumann LM. Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. Am J Med Genet A. 2004 Oct 1;130A(2):138-45. Review. PubMed PMID: 15372515.

Mohney BG, Pulido JS, Lindor NM, Hogan MC, Consugar MB, Peters J, Pankratz VS, Nasr SH, Smith SJ, Gloor J, Kubly V, Spencer D, Nielson R, Puffenberger EG, Strauss KA, Morton DH, Eldahdah L, Harris PC. A Novel Mutation of LAMB2 in a Multigenerational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome. Ophthalmology. 2011 Jan 12. PubMed PMID: 21236492.