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Disease Profile

Amish lethal microcephaly

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

Q02

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)

Microcephaly, Amish type; MCPHA

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 99742

Definition
A very rare syndrome characterized by extreme microcephaly and early death, within the first year.

Epidemiology
It has been described only in the Old Order Amish of Lancaster County Pennsylvania. In this population, birth prevalence is about 1/500.

Clinical description
Microcephaly is a microcephalia vera (MV), evident at birth or through 22-week fetal ultrasound. Affected children have high urinary levels of alpha-ketoglutaric acid.

Etiology
All affected infants are homozygous for the same mutation of the SLC25A19 gene on chromosome 17 (17q25.3).

Genetic counseling
The condition follows an autosomal recessive pattern of inheritance.

Prognosis
Prognosis is very poor: the average life span of affected infants is between five and six months.

Visit the Orphanet disease page for more resources.

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
80%-99% of people have these symptoms
Cerebellar vermis hypoplasia
0001320
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Irritability
Irritable
0000737
Metabolic acidosis
0001942
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Optic atrophy
0000648
Organic aciduria
0001992
Severe global developmental delay
0011344
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
30%-79% of people have these symptoms
Agenesis of corpus callosum
0001274
Limb hypertonia
Increased muscle tone of arm or leg
0002509
Lissencephaly
Fewer or absent grooves in brain
0001339
Muscular hypotonia
Low or weak muscle tone
0001252
Osteoporosis
0000939
Spina bifida
0002414
Temperature instability
0005968
Ventriculomegaly
0002119
5%-29% of people have these symptoms
Bilateral tonic-clonic seizure
Grand mal seizures
0002069
Cleft soft palate
0000185
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Decreased skull ossification
Decreased bone formation of skull
0004331
Hepatomegaly
Enlarged liver
0002240
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Congenital onset
Symptoms present at birth
0003577
Flexion contracture
Flexed joint that cannot be straightened
0001371
Lactic acidosis
Increased lactate in body
0003128
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Partial agenesis of the corpus callosum
0001338
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253

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.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

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 Amish lethal microcephaly. 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. 
  • 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 Amish lethal microcephaly. Click on the link to view a sample search on this topic.