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Disease Profile

Microphthalmia with linear skin defects syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q11.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MCOPS7; MLS syndrome; Microphthalmia with linear skin defects;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Eye diseases;

Summary

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.

Symptoms

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

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.

Medical Terms Other Names
Learn More:
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 rectum morphology
Abnormality of the rectum
Anomaly of the rectum

[ more ]

0002034
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
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

Diagnosis

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.

Learn more

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.

References

  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; https://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.

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