microcoria

RAB18 Deficiency

Clinical Characteristics

Ocular Features:

Microphthalmia with microcornea, lens opacities, small and unresponsive pupils, and optic atrophy are the outstanding ocular features of this syndrome. The eyes appear deeply set. Some but not all have ERG evidence of rod and cone dysfunction. The VEP is usually abnormal. Short palpebral fissures have been described.

Systemic Features:

Patients with the micro syndrome have many somatic and neurologic abnormalities. Infants usually have feeding problems that is sometimes accompanied by gastroesophageal reflux. Some degree of psychomotor retardation and developmental delays is common. Both spasticity and hypotonia have been described. Some patients have seizures. Facial hypertrichosis, anteverted ears, and a broad nasal bridge are often noted. There may be absence of the corpus callosum while diffuse cortical and subcortical atrophy, microgyria, and pachygyria may be evident on MRI imaging. Hypogenitalism may be a feature in both sexes. Males may also have cryptorchidism and a micropenis while females can have hypoplasia of the labia minora and clitoris and a small introitus. Microcephaly is inconsistently present.

Genetics

This is a clinically and genetically heterogeneous disorder caused by homozygous mutations in at least 4 genes: RAB3GAP1 (WARBM1), RAB3GAP2 (WARBM2), RAB18 (WARBM3), and TBC1D20 (WARBM4).

Pedigree:

Autosomal recessive

Treatment

Treatment Options:

No effective treatment is available. Vision remains subnormal even after cataracts are removed. Nutrition may be improved with placement of a gastrostomy tube.

References

Article Title:

Warburg micro syndrome type 1 associated with peripheral neuropathy and cardiomyopathy

Kabzinska D, Mierzewska H, Senderek J, Kochanski A. Warburg micro syndrome type 1 associated with peripheral neuropathy and cardiomyopathy. Folia Neuropathol. 2016;54(3):273-281.

PubMed ID:

27764520

Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation

Handley MT, Carpanini SM, Mali GR, Sidjanin DJ, Aligianis IA, Jackson IJ, FitzPatrick DR. Warburg Micro syndrome is caused by RAB18 deficiency or dysregulation. Open Biol. 2015 Jun;5(6). pii: 150047. doi: 10.1098/rsob.150047.

PubMed ID:

26063829

New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish

Morris-Rosendahl DJ, Segel R, Born AP, Conrad C, Loeys B, Brooks SS, M?oller L,Zeschnigk C, Botti C, Rabinowitz R, Uyanik G, Crocq MA, Kraus U, Degen I, Faes F. New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish. Eur J Hum Genet. 2010 Oct;18(10):1100-6.

PubMed ID:

20512159

Phenotypic variability in Micro syndrome: report of new cases

Abdel-Salam GM, Hassan NA, Kayed HF, Aligianis IA. Phenotypic variability in Micro syndrome: report of new cases. Genet Couns. 2007;18(4):423-35.

PubMed ID:

18286824

Autosomal recessive microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism

Warburg M, Sjo O, Fledelius HC, Pedersen SA. Autosomal recessive microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy, and hypogenitalism. Micro syndrome. Am J Dis Child. 1993 Dec;147(12):1309-12.

PubMed ID:

8249951

Pierson Syndrome

Clinical Characteristics

Ocular Features:

Microcoria is the most consistent ocular feature but is not present in some families. It is congenital and sometimes seen with iris hypoplasia. Glaucoma and lens opacities (including posterior lenticonus sometimes) are present in one-fourth of patients. Corneal size varies with some patients having apparent macrocornea which can lead to the mistaken diagnosis of buphthalmos. Pigment mottling and clumping is common in the retina and the ERG can show changes characteristic of cone-rod dystrophy. Retinal thinning is often present as well. Non-rhegmatogenous retinal detachments occur in 24% of patients and optic atrophy is seen in some individuals. There is considerable interocular, intrafamilial, and interfamilial variability in these signs.

Systemic Features:

The primary and most consistent systemic problem is progressive renal disease. Congenital nephrotic syndrome with proteinuria, hypoalbuminemia and hypertension is characteristic. Renal failure eventually occurs although the rate of progression varies. Most patients require a renal transplant for end-stage kidney disease in the first decade of life. Kidney histology shows glomerulosclerosis, peritubular scarring, and diffuse mesangial sclerosis. Hypotonia and muscle weakness are sometimes present and congenital myasthenia has been reported. Severe global psychomotor retardation is common and many infants never achieve normal milestones.

Genetics

This is an autosomal recessive disorder resulting from homozygous mutations in the LAMB2 gene located at 3p21. The normal gene encodes laminin beta-2 that is strongly expressed in intraocular muscles which may explain the hypoplasia of ciliary and pupillary muscles in Pierson syndrome. Mutations in this gene are often associated with nephronophthisis but ocular abnormalities are not always present.

Microcoria is also a feature of the autosomal dominant ocular condition known as congenital microcoria (156600).

Pedigree:

Autosomal recessive

Treatment

Treatment Options:

Kidney replacement can restore renal function. Glaucoma, cataracts, and retinal detachments require the usual treatment but patient selection is important due to the neurological deficits. Lifelong monitoring is essential.

References

Article Title:

Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene

Arima M, Tsukamoto S, Akiyama R, Nishiyama K, Kohno RI, Tachibana T, Hayashida A, Murayama M, Hisatomi T, Nozu K, Iijima K, Ohga S, Sonoda KH. Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ss2 gene. J AAPOS. 2018 Aug 16. pii: S1091-8531(18)30497-X. doi: 10.1016/j.jaapos.2018.03.016. [Epub ahead of print].

PubMed ID:

30120985

A Novel Mutation of LAMB2 in a Multigenerational Mennonite Family Reveals a New Phenotypic Variant of Pierson Syndrome

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 ID:

21236492

Ophthalmological aspects of Pierson syndrome

Bredrup C, Matejas V, Barrow M, Bl?deghov?deg K, Bockenhauer D, Fowler DJ, Gregson RM, Maruniak-Chudek I, Medeira A, Mendon?ssa EL, Kagan M, Koenig J, Krastel H, Kroes HY, Saggar A, Sawyer T, Schittkowski M, Swietli?Nski 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 ID:

18672223

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

Zenker M, Tralau T, Lennert T, Pitz S, Mark K, Madlon H, Dotsch J, Reis A, M?ontefering 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 ID:

15372515

You are here

Search For A Disorder