Warburg Micro Syndrome 1

Alternative Names

  • WARBM1
  • Micro Syndrome
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Other congenital malformations

OMIM Number

600118

Mode of Inheritance

Autosomal recessive

Gene Map Locus

2q21.3

Description

Warburg first described this extremely rare autosomal recessive genetic disorder in 1993. The disease is characterized by severe mental retardation, microcephaly, hypoplasia of the corpus callosum, microgenitalia and characteristic ocular findings, like microphthalmia, microcornea, congenital cataract, and optic atrophy. The patients also present with dysmorphic features, such as beaked nose with a prominent nasal root, large anteverted ears, hypertrichosis, micrognathia, and highly arched palate. Seizures and/or limb contractures may develop in some patients. Delayed puberty is commonly observed.

Up until now, only 24 definite cases of this disease have been reported. Diagnosis of the disease involves a thorough ocular examination, and brain scans. Although the RAB3GAP gene has been implicated in micro syndrome, to date no genetic test is available for its diagnosis. Treatment is symptomatic. Since congenital cataract is the most common symptom of the disease, most treatment strategies would target it. Physiotherapy is also an important component of the treatment plan, since most patients develop limb contractures and hypotonia.

Molecular Genetics

Micro syndrome has been found to be linked to the RAB3GAP gene, located on chromosome 2. This gene encodes a protein, which is implicated in regulated neurodevelopmental processes, such as proliferation, migration and differentiation before synapse formation, non-synaptic vesicular release of neurotransmitters, and regulated exocytosis of hormones. Mutations in the gene coding for the catalytic region of this protein have been found in patients of micro syndrome. It is presumed that the mutations lead to defects in the vesicular transport and exocytosis of neurotransmitters and hormones.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
600118.1.1LebanonFemaleYesYes Bilateral microphthalmos; Cataract; Ce... NM_001172435.2:c.2011C>THomozygousAutosomal, RecessiveMegarbane et al. 1999; Aligianis et al. 2005
600118.1.2LebanonFemaleYesYes Bilateral microphthalmos; Cataract; Ce... NM_001172435.2:c.2011C>THomozygousAutosomal, RecessiveMegarbane et al. 1999; Aligianis et al. 2005 Cousin of 600118.1.1
600118.1.3LebanonFemaleYesYes Bilateral microphthalmos; Cataract; Ce... NM_001172435.2:c.2011C>THomozygousAutosomal, RecessiveMegarbane et al. 1999; Aligianis et al. 2005 Cousin of 600118.1.1
600118.1.4LebanonMaleYesYes Bilateral microphthalmos; Cataract; Ce... NM_001172435.2:c.2011C>THomozygousAutosomal, RecessiveMegarbane et al. 1999; Aligianis et al. 2005 Cousin of 600118.1.1
600118.2MoroccoUnknownYesYes Postnatal microcephaly; Severe global d... NM_001172435.2:c.475_478delHomozygousAutosomal, RecessiveAligianis et al. 2005 Proband from a large...

Other Reports

Lebanon

Megarbane et al. (1999) described four children (one male and three females) from a highly inbred Shiite Muslim family from southern Lebanon with hypotonia, microcephaly, microphthalmia, congenital cataract, ptosis, short stature, severe mental retardation, and cerebral malformations

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