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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.
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
Age of onset
Infancy
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.
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.
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.
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.
X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.
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.
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.
Not applicable
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.
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.
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.
All affected infants are homozygous for the same mutation of the SLC25A19 gene on chromosome 17 (17q25.3).
The condition follows an autosomal recessive pattern of inheritance.
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 | |
|
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] |
0000252 | |
|
Little lower jaw
Small jaw
Small lower jaw
[ more ] |
0000347 | |
| Optic atrophy | 0000648 | |
| Organic aciduria | 0001992 | |
| Severe global |
0011344 | |
| Sloping forehead |
Inclined forehead
Receding forehead
[ more ] |
0000340 |
| 30%-79% of people have these symptoms | ||
| Agenesis of |
0001274 | |
| Limb hypertonia |
Increased muscle tone of arm or leg
|
0002509 |
| Lissencephaly |
Fewer or absent grooves in brain
|
0001339 |
| Muscular |
Low or weak muscle tone
|
0001252 |
| 0000939 | ||
| Spina bifida | 0002414 | |
| Temperature instability | 0005968 | |
| Ventriculomegaly | 0002119 | |
| 5%-29% of people have these symptoms | ||
| Bilateral tonic-clonic |
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 | ||
| 0000007 | ||
| Cerebellar hypoplasia |
Small cerebellum
Underdeveloped cerebellum
[ more ] |
0001321 |
|
Symptoms present at birth
|
0003577 | |
| Flexion |
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.