OMIM ID:
Microphthalmia, Syndromic 7
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Microphthalmia and rarely clinical anophthalmia are the ocular hallmarks of this disorder. Corneal leukomas and some degree of sclerocornea are usually present as well. Orbital cysts have been observed. Other less consistent findings include iridocorneal adhesions, glaucoma, microcornea, cataracts, aniridia, persistence of the anterior hyaloid artery and other vitreous opacities, and patchy hypopigmentation of the RPE.
Systemic Features
The skin on the nose, cheeks and neck has linear red rashes and scar-like lesions. Biopsy of these has revealed smooth muscle hemartomata rather than simple dermal aplasia. There may be some healing of the skin defects. The corpus callosum is sometimes absent. Diaphragmatic hernias are often present. Cardiac abnormalities include hypertrophic cardiomyopathy, arrhythmias, and septal defects. Preauricular pits and hearing loss have been found in some patients. Patients may be short in stature and some have nail dysplasia. GU and GI anomalies may be present.
Genetics
Inheritance
This is an X-linked dominant disorder with lethality in the hemizygous male. Many patients (79%) have interstitial deletions of the Xp22.2 region of the X chromosome. Sequence analysis of this region has revealed heterozygous point mutations in the HCCS gene (Xp22.2) in numerous other patients. In several additional cases deleterious mutations have been found in the X-linked COX7B gene. However, familial occurrence is uncommon. X chromosome inactivation may be skewed with the abnormal X being inactive in virtually all cases. Several 46 XX males with this syndrome have been described.
Goltz syndrome (305600), also called focal dermal hypoplasia, may have similar skin and ocular findings but the limb anomalies are not found in the disorder described here. Goltz syndrome (305600) is the result of mutations in PORCN at another locus on the X chromosome and is thus unrelated.
Other X-linked dominant disorders with lethality in hemizygous males and abnormalities in skin and the eye are Incontinentia pigmenti (308300) and Aicardi syndrome (304050). The skin lesions and ocular anomalies are dissimilar to those in MLS and they often have far more severe CNS abnormalities. Further, the mutation causing Aicardi is in the NEMO (IKBKG) gene at another location on the X chromosome.
Pedigree
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.