MICROFTALMIA sindrome
OMIM 309801 (MCOPS7)
OMIM 156845 (MITF)
GeneReviews MICROPHTHALMIA
Clinical characteristics
Microphthalmia with linear skin defects (MLS) syndrome is characterized by unilateral or bilateral microophthalmia and/or anophthalmia and linear skin defects, usually involving the face and neck, which are present at birth and heal with age, leaving minimal residual scarring. Other findings can include central nervous system involvement (e.g., structural anomalies, infantile seizures), developmental delay, heart defects (e.g., hypertrophic cardiomyopathy, oncocytic cardiomyopathy, arrhythmias), short stature, diaphragmatic hernia, nail dystrophy, preauricular pits and hearing loss, and genitourinary malformations. Inter- and intrafamilial variability is considerable.
Diagnosis/testing
Diagnosis is based on clinical findings and detection of either a chromosomal abnormality that results in monosomy for Xp22 or mutation of HCCS, the only gene known to be associated with MLS syndrome.
Management
Treatment of manifestations: Use of a prosthesis for severe microphthalmia and anophthalmia; routine dermatologic care for significant skin lesions; treatment of seizures and/or other neurologic abnormalities by a pediatric neurologist; appropriate developmental stimulation and special education as indicated for developmental delay; routine care for other malformations when present.
Surveillance: Monitoring and follow-up with ophthalmologist, dermatologist, pediatric neurologist, cardiologist, or other professionals as needed.
Genetic counseling
MLS syndrome is inherited in an X-linked manner and mainly affects females as it is usually lethal in males. Most cases are simplex (i.e., a single occurrence in a family), but familial occurrences have been described. Women who are affected or have either the deleted X chromosome or an HCCS pathogenic variant have a 50% chance of passing the genetic alteration to each offspring. Because male conceptuses with the deleted X chromosome or the HCCS pathogenic variant are typically nonviable, the likelihood of a live-born affected child is less than 50%. Carrier testing for at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing genetic alteration has been identified in an affected family member.
