Microphthalmia with linear skin defects syndrome

Author: Dr Delwyn Dyall-Smith FACD, Dermatologist, Australia, 2011.

What is microphthalmia with linear skin defects syndrome?

Microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a rare genetic neurodevelopmental disorder that presents at birth in females. The two major features are eye and skin abnormalities. Neurologic and cardiovascular problems can also be associated.

MLS syndrome is also known as MIDAS syndrome (MIcrophthalmia, Dermal Aplasia, Sclerocornea) or Gazali-Temple syndrome.

Who gets MLS syndrome and why?

MLS syndrome is an X-linked dominant genetic condition. It predominantly affects females. Mother to daughter transmission has been reported. X-chromosome inactivation influences the clinical appearance of the syndrome.

Only a single copy of the mutated gene is required to have an effect. In XY males, as they have only one X chromosome, the effect is lethal before birth. XX Males (eg 47:XXY or 46:XX with Xp;Y translocation) can survive and show the typical clinical features of MLS syndrome. Females have two copies of the X chromosome, and therefore affected females have one normal and one abnormal or deleted gene. To date, where the abnormality has been identified, it has usually involved a deletion in a specific region of the X chromosome. Point mutations (missense and nonsense) have been reported rarely. However, not all cases of MLS syndrome have had a mutation confirmed.

Mutations in the HCCS gene, located on Xp22.2, affect the holocytochrome-c type synthetase (also known as heme lyase). This enzyme is important in mitochondria for the production of cytochrome c, involved in oxidative phosphorylation and cell death (apoptosis)

Clinical features of MLS syndrome

The two major organs affected in MLS syndrome are the eye and the skin and these features are present at birth.

Microphthalmia

Microphthalmia is the name used to describe eyeballs that are smaller than usual. One or both eyes may be affected. It does not cause ‘anophthalmia’, which means absent eyeballs, although that name has incorrectly been used for some cases. In MLS syndrome the cornea is often cloudy (sclerocornea).

Linear skin defects

Skin is involved in nearly all cases. Characteristically there are irregular, linear skin defects localised to the face and neck. These may correspond with Blaschko lines. At birth the lines are red but they heal to leave brown pigmented areas.

Other features of MLS syndrome

Some patients have had only the eye or only the skin signs, in combination with other less common features. These other features are described in the table below.

Heart
  • Involved in approximately 18%
  • Cardiomyopathy (heart muscle defect)
  • Septal defect (hole in the heart)
  • Arrythmias (irregular heart beat)
Brain
  • Absent corpus callosum
  • Infantile seizures
  • Microcephaly (small brain)
  • Enlarged ventricles
  • Mild to severe mental retardation (25%)
Eye
  • Chorioretinal abnormalities (the lining of the eyeball)
  • Blepharophimosis (narrowed eye opening)
  • Orbital cysts (lumps in the eye socket)
Diaphragmatic hernia
  • Gap in diaphragm (muscle under the ribs used for breathing)
  • Respiratory distress (difficulty breathing)
Stature
  • Often short
Urogenital system
  • Anomalies of internal and external genitalia

There can be considerable variation in the clinical presentation, even within the one family.

How is MLS syndrome diagnosed?

MLS syndrome is initially a clinical diagnosis based on the characteristic eye and skin changes.

Chromosome (karyotype) studies commonly show an obvious difference in one of the X chromosomes, characteristically a deletion of the short arm. The HCCS gene can be sequenced for mutations in research laboratories if the deletion is not apparent.

Biopsy from a skin lesion has been reported from only one patient and showed a smooth muscle hamartoma.

MLS syndrome may need to be distinguished from focal dermal hypoplasia or Goltz syndrome (MIM305600), another X-linked syndrome with eye and skin abnormalities that predominantly affects females. However skeletal abnormalities such as syndactyly (joined fingers or toes) or clefting of the hands or feet are not seen in MLS syndrome. The gene responsible for focal dermal hypoplasia is the PORCN gene on Xp11.23.

Aicardi syndrome (MIM304050) may also need to be excluded as the eye and brain are similarly affected, only in females. However the skin is not involved. The gene causing this syndrome has not yet been identified, but it has been localised to Xp22.

Treatment of MLS syndrome

Treatment is directed at the specific symptoms as they arise. There is no cure.

The skin lesions heal by themselves leaving brown marks.

Related information

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