Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development (MCLMR) is an autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes (summary by Ostergaard et al., 2012). Robitaille et al. (2014) found that MCLMR includes a broader spectrum of ocular disease, including retinal detachment with avascularity of the peripheral retina, and noted phenotypic overlap with familial exudative vitreoretinopathy (FEVR; see EVR1, 133780). Birtel et al. (2017) observed intrafamilial and intraindividual variability in retinal phenotype, and noted that syndromic manifestations in some patients are too subtle to be detected during a routine ophthalmologic evaluation. Variable expressivity and reduced penetrance have also been observed in some families (Jones et al., 2014; Li et al., 2016). Autosomal recessive forms of microcephaly with chorioretinopathy have been reported (see 251270). See also Mirhosseini-Holmes-Walton syndrome (autosomal recessive microcephaly with pigmentary retinopathy and impaired intellectual development; 268050), which has been mapped to chromosome 8q21.3-q22.1.

Microcephaly and chorioretinopathy is an autosomal recessive developmental disorder characterized by delayed psychomotor development and visual impairment, often accompanied by short stature (summary by Martin et al., 2014). Genetic Heterogeneity of Microcephaly and Chorioretinopathy See also MCCRP2 (616171), caused by mutation in the PLK4 gene (605031) on chromosome 4q27, and MCCRP3 (616335), caused by mutation in the TUBGCP4 gene (609610) on chromosome 15q15. An autosomal dominant form of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation is caused by heterozygous mutation in the KIF11 gene (148760) on chromosome 10q23. See also Mirhosseini-Holmes-Walton syndrome (autosomal recessive pigmentary retinopathy and mental retardation; 268050), which has been mapped to chromosome 8q21.3-q22.1.

Any microcephaly and chorioretinopathy in which the cause of the disease is a mutation in the TUBGCP4 gene.