What is the definition of Microphthalmia with Linear Skin Defects Syndrome?

Microphthalmia with linear skin defects syndrome (MLS syndrome) is a genetic condition that affects the eyes and skin. It is mainly found in females and is characterized by small or poorly developed eyes (microphthalmia) and characteristic linear skin markings on the head and neck. The signs and symptoms of this condition may include abnormalities of the brain, heart, and genitourinary system. Other symptoms may include short stature, developmental delay, and finger and toenails that do not grow normally (nail dystrophy). MLS syndrome is typically caused by either a deletion of certain genetic material on the p (short) arm of the X chromosome or by a mutation in the HCCS gene. In some cases, it may be caused by mutations in the COX7B and NDUFB11 genes, (also located on the X chromosome). According to the mutated gene, the disease may be classified in three subtypes. This condition is inherited in an X-linked manner and is thought to result in serious early developmental concerns in males, leading to almost no males with this condition surviving to delivery. Although there is no specific treatment or cure for MLS syndrome, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options based on each person’s symptoms.

What are the alternative names for Microphthalmia with Linear Skin Defects Syndrome?

  • MCOPS7
  • MLS syndrome
  • Microphthalmia with linear skin defects
  • Microphthalmia Dermal Aplasia and Sclerocornea syndrome
  • MIDAS syndrome
  • Syndromic microphthalmia type 7
  • Micropthalmia syndromic 7
  • Linear skin defects with multiple congenital anomalies 1
  • Microphthalmia-dermal aplasia-sclerocornea syndrome

What are the causes for Microphthalmia with Linear Skin Defects Syndrome?

MLS syndrome is most commonly caused by mutations in the HCCS gene or a deletion of genetic material on the X chromosome that includes the HCCS gene. This gene provides instructions for a protein that is involved in many tissues of the body-particularly the mitochondria. The mitochondria are the structures in our cells that produce energy. The protein is additionally involved in the process in which damaged cells are destroyed (apoptosis). A mutations within the HCCS gene or loss of the gene entirely may lead to an issue with energy production and the ability to destroy damaged cells. In some cases, MLS syndrome may be caused by mutations in the COX7B and NDUFB11 genes, (also located on the X chromosome).

What are the symptoms for Microphthalmia with Linear Skin Defects Syndrome?

The signs and symptoms of MLS syndrome differ among individuals; however, the condition is characterized by eye and skin findings. Most commonly, individuals are found to have small or poorly formed eyes (microphthalmia). One or both eyes may also be missing (anophthalmia). People with this condition usually also have what is described as linear skin defects on the head and neck. These are characteristic skin markings that follow the paths along which cells migrate as the skin develops before birth. These paths are known as the lines of Blaschko.  Other eye symptoms in people with MLS syndrome may include:
  • Poor development of the clear layer that covers the front of the eye (sclerocornea)
  • Cysts in the cavity of the skull where the eye is located (orbital cysts)
  • Congenital glaucoma
Other symptoms may include:
  • Brain malformations
  • Developmental delay
  • Intellectual disability
  • Short stature
  • An abnormal opening in the diaphragm (diaphragmatic hernia)
  • Finger and toenails that do not grow normally (nail dystrophy)
  • A small pit in the outside part of the ear (preauricular pits)
  • Hearing loss
  • Heart defects 
  • Abnormalities in the development of the genitals and urinary tract
  • A missing or blocked opening in the anus

Is Microphthalmia with Linear Skin Defects Syndrome an inherited disorder?

MLS syndrome is inherited in an X-linked manner. This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition. There is nothing either parent can do, before or during a pregnancy, to cause a child to have this condition. Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females. Males that inherit MLS syndrome usually have very serious developmental concerns. Almost no males are born with this condition. If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene. Most cases of MLS syndrome occur in people with no history of the disorder in their family. These cases usually result from the deletion of a piece of the X chromosome during the formation of the eggs or sperm or in early fetal development. They may also result from a new (de novo) mutation in the HCCS gene.