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Disease Profile

Multiple congenital anomalies-hypotonia-seizures syndrome type 2

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

Infancy

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ICD-10

Q87.8

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)

MCAHS2; Early infantile epileptic encephalopathy 20; MCAHS type 2

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

Multiple congenital anomalieshypotoniaseizures syndrome type 2 (MCAHS2) is a genetic neurodevelopmental disorder characterized by distinctive facial features, low muscle tone (hypotonia) at birth, myoclonic seizures (which cause jerks or twitches of the upper body, arms, or legs), and various other problems involving the central nervous system, heart, and urinary system. Specific symptoms (especially those not involving the nervous system) and severity vary from person to person, but most children develop severe developmental delay and intellectual disability. This condition is caused by mutations in the PIGA gene on the X chromosome and inheritance is X-linked recessive, so it typically affects boys.[1] However, in some cases, MCAHS2 is not inherited from a parent and is the result of a new mutation occurring for the first time in a person with MCAHS2 (a de novo mutation).[2] Treatment depends on the symptoms present and aims to control symptoms and increase quality of life. The long-term outlook and life expectancy varies depending on severity. Some children with MCAHS2 do not survive beyond infancy.[3]

Symptoms

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
5%-29% of people have these symptoms
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Duplicated collecting system
0000081
Elevated alkaline phosphatase
Greatly elevated alkaline phosphatase
High serum alkaline phosphatase
Increased alkaline phosphatase
Increased serum alkaline phosphatase

[ more ]

0003155
Hepatomegaly
Enlarged liver
0002240
Ichthyosis
0008064
Polyhydramnios
High levels of amniotic fluid
0001561
Seborrheic dermatitis
0001051
Vesicoureteral reflux
0000076
1%-4% of people have these symptoms
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
Percent of people who have these symptoms is not available through HPO
Abnormality of skin pigmentation
Abnormal pigmentation
Abnormal skin color
Abnormal skin pigmentation
Abnormality of pigmentation
Pigmentary changes
Pigmentary skin changes
Pigmentation anomaly

[ more ]

0001000
Abnormality of the pons
0007361
Absent septum pellucidum
0001331
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Birth length greater than 97th percentile
0003517
Central hypotonia
0011398
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Cerebral visual impairment
0100704
Coarse facial features
Coarse facial appearance
0000280
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Delayed myelination
0012448
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

0002714
Elevated hepatic iron concentration
Increased iron concentration in liver
0012465
Epileptic encephalopathy
0200134
Flexion contracture
Flexed joint that cannot be straightened
0001371
Generalized myoclonic seizure
0002123
Gingival overgrowth
Gum enlargement
0000212
Gliosis
0002171
Global developmental delay
0001263
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hydrops fetalis
0001789
Hyperreflexia
Increased reflexes
0001347
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypsarrhythmia
0002521
Large fontanelles
Wide fontanelles
0000239
Large for gestational age
Birth weight > 90th percentile
Birthweight > 90th percentile

[ more ]

0001520
Lower limb spasticity
0002061
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Malar flattening
Zygomatic flattening
0000272
Microdontia
Decreased width of tooth
0000691
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Micropenis
Short penis
Small penis

[ more ]

0000054
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Narrow mouth
Small mouth
0000160
Neuronal loss in central nervous system
Loss of brain cells
0002529
Olfactory lobe agenesis
Olfactory lobe absence
0001341
Overfolded helix
Overfolded ears
0000396
Overgrowth
General overgrowth
0001548
Postnatal microcephaly
0005484
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Short neck
Decreased length of neck
0000470
Small nail
Small nails
0001792
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Triangular mouth
Triangular shaped mouth
0000207
Upp

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.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        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.

        In-Depth Information

        • 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. 
        • 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 Multiple congenital anomalies-hypotonia-seizures syndrome type 2. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 2; MCAHS2. Online Mendelian Inheritance in Man (OMIM). May 22, 2014; https://www.omim.org/entry/300868. Accessed 10/2/2015.
            2. Xie LL, Song XJ, Li TY, Jiang L. A novel germline PIGA mutation causes early-onset epileptic encephalopathies in Chinese monozygotic twins.. Brain Dev. March 1, 2018; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/29502866.
            3. Low KJ, James M, Sharples PM, Eaton M, Jenkinson S, Study DDD, Smithson SF. A novel PIGA variant associated with severe X-linked epilepsy and profound developmental delay. Seizure. March, 2018; Epub 2018 Jan 31:https://www.ncbi.nlm.nih.gov/pubmed/29414593.

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