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Microphthalmia with linear skin defects syndrome


Other Names:
MCOPS7; MLS syndrome; Microphthalmia with linear skin defects; 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 See More
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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.[1][2] 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).[1][2] 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.[3][4][5] 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.[1] 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.

Last updated: 5/19/2017
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.[6][1] 

Other eye symptoms in people with MLS syndrome may include:[6]
  • 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:[4][6]
  • 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


Last updated: 5/23/2017

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 87 |
Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Anophthalmia
Absence of eyeballs
Failure of development of eyeball
Missing eyeball
No eyeball
[ more ] 		0000528
Congenital diaphragmatic hernia 0000776
Dermal atrophy
Skin degeneration
0004334
Erythema 0010783
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Microphthalmia
Abnormally small eyeball
0000568
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Sclerocornea
Hardening of skin and connective tissue
0000647
30%-79% of people have these symptoms
Abnormal cardiac septum morphology 0001671
Abnormal eyelash morphology
Abnormal eyelashes
Abnormality of the eyelashes
Eyelash abnormality
[ more ] 		0000499
Abnormal facial shape
Unusual facial appearance
0001999
Abnormal nasolacrimal system morphology 0000614
Abnormality of retinal pigmentation 0007703
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Hypopigmented skin patches
Patchy loss of skin color
0001053
Mandibular aplasia
Failure of development of lower jaw
Missing lower jaw
[ more ] 		0009939
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw
[ more ] 		0000278
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe
[ more ] 		0003510
Vitritis 0011531
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
Wide nose
Broad nose
Increased breadth of nose
Increased nasal breadth
Increased nasal width
Increased width of nose
[ more ] 		0000445
5%-29% of people have these symptoms
Abnormal fallopian tube morphology 0011027
Abnormal testis morphology
Abnormality of the testis
0000035
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality
[ more ] 		0000682
Abnormality of the anus 0004378
Abnormality of the nail 0001597
Abnormality of the rectum
Anomaly of the rectum
0002034
Absent septum pellucidum 0001331
Agenesis of corpus callosum 0001274
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia
[ more ] 		0000062
Amblyopia
Lazy eye
Wandering eye
[ more ] 		0000646
Aphasia
Difficulty finding words
Losing words
Loss of words
[ more ] 		0002381
Blindness 0000618
Chorioretinal dysplasia 0007731
Cleft earlobe 0011265
Clitoral hypertrophy
Enlarged clitoris
0008665
Dysphasia 0002357
Echolalia
Echoing another person's speech
0010529
Epispadias 0000039
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Functional motor deficit 0004302
Glaucoma 0000501
Global developmental delay 0001263
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypospadias 0000047
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Male pseudohermaphroditism 0000037
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Mitral regurgitation 0001653
Mitral valve prolapse 0001634
Mutism
Inability to speak
Muteness
[ more ] 		0002300
Posterior embryotoxon 0000627
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
Respiratory failure 0002878
Retinal dysplasia 0007973
Retinal dystrophy
Breakdown of light-sensitive cells in back of eye
0000556
Sacral dimple
Spinal dimple
0000960
Specific learning disability 0001328
Status epilepticus
Repeated seizures without recovery between them
0002133
Tricuspid regurgitation 0005180
Tricuspid valve prolapse 0001704
Visual loss
Loss of vision
Vision loss
[ more ] 		0000572
1%-4% of people have these symptoms
Intellectual disability, progressive
Mental retardation, progressive
Progressive mental retardation
[ more ] 		0006887
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Anal atresia
Absent anus
0002023
Anteriorly placed anus 0001545
Asymmetric, linear skin defects 0007398
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Chordee 0000041
Colpocephaly 0030048
Histiocytoid cardiomyopathy 0005152
Hypoplasia of the uterus
Small uterus
Underdeveloped uterus
[ more ] 		0000013
Iris coloboma
Cat eye
0000612
Micropenis
Short penis
Small penis
[ more ] 		0000054
Overriding aorta 0002623
Ovotestis 0012861
Pigmentary retinopathy 0000580
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
X-linked dominant inheritance 0001423
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Last updated: 7/1/2020
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.[1]

In some cases, MLS syndrome may be caused by mutations in the COX7B and NDUFB11 genes, (also located on the X chromosome).[5]
Last updated: 5/23/2017
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.[1] 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.[1]
Last updated: 5/23/2017

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Microphthalmia with linear skin defects syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Microphthalmia with linear skin defects syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Microphthalmia with linear skin defects syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Microphthalmia with linear skin defects syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. microphthalmia with linear skin defects syndrome. Genetics Home Reference. October 2009; https://ghr.nlm.nih.gov/condition/microphthalmia-with-linear-skin-defects-syndrome.
  2. Microphthalmia with linear skin defects syndrome. Orphanet. September 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2556.
  3. Van Rahden VA, Fernandez-Vizarra E, Alawi M, et al. Encoding a Complex I Component of the Mitochondrial Respiratory Chain, Cause Microphthalmia with Linear Skin Defects Syndrome.. American Journal of Human Genetics. April 2, 2015; 96(4):640-650. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385192/.
  4. Van Rahden VA, Rau I, Fuchs S, et al. Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome. Orphanet Journal of Rare Diseases. April 15, 2014; 9(53):https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021606/.
  5. O'Neill MJF. Linear Skin Defects With Multiple Congenital Anomalies 1. Online Mendelian Inheritance in Man (OMIM). 9/23/2016; https://www.omim.org/entry/309801.
  6. Morleo M, Franco B. Microphthalmia with Linear Skin Defects Syndrome. GeneReviews. August 18, 2011; https://www.ncbi.nlm.nih.gov/books/NBK7041.