Rare Hematology News

Disease Profile

Congenital intrauterine infection-like 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

Q87.8

Inheritance

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

no.svg

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

rnn-autosomalrecessive.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

Band-like calcification with simplified gyration and polymicrogyria ; BLCPMG ; BLC-PMG;

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: 1229

Definition
Congenital intrauterine infection-like syndrome is characterised by the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent.

Epidemiology
More than 30 cases have been described in the literature so far.

Clinical description
The clinical presentation of the reported cases is rather heterogeneous with variable manifestations including intrauterine growth retardation, hepatosplenomegaly, hyperbilirubinaemia, cerebellar hypoplasia or atrophy, and congenital cataract. Affected individuals with associated thrombocytopaenia have also been reported but it has been suggested that these patients may have a distinct subtype.

Etiology
The cause remains unknown.

Diagnostic methods
Diagnosis relies on the clinical picture and requires exclusion of intrauterine infections.

Differential diagnosis
Congenital intrauterine infection-like syndrome shows considerable clinical overlap with Aicardi-Goutieres syndrome (AGS, see this term). The two syndromes were reported to differ by the presence of cerebrospinal fluid anomalies (CSF leucocytosis and elevated IFN-alpha levels) in AGS and hepatic dysfunction, congenital microcephaly and thrombocytopaenia in congenital intrauterine infection-like syndrome. However, as the clinical manifestations of both syndromes show significant variability, it has been suggested that AGS and congenital intrauterine infection-like syndrome represent different presentations of the same disease. The differential diagnosis should also include other syndromes characterised by microcephaly and intracranial calcification such as Cockayne syndrome, COFS syndrome (which is usely considered as the neonatal form of Cockayne syndrome) and Hoyeraal-Hreidarsson syndrome (the neonatal presentation of dyskeratosis congenita syndrome; see these terms), some cases of mitochondrial encephalomyopathy, and pseudohypoarathyroidism. Ancient cases may have been reported as ``Fahr disease'', an outdated, causally heterogeneous clinical entity that encompasses several entities with intracranial calcifications.

Genetic counseling
Several familial cases, compatible with an autosomal recessive pattern of inheritance, have been described.

Management and treatment
Treatment is symptomatic only.

Prognosis
The prognosis is variable but can be severe with several of the reported patients dying within the first year of life.

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
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Hyperreflexia
Increased reflexes
0001347
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Seizure
0001250
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
30%-79% of people have these symptoms
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
5%-29% of people have these symptoms
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Opacification of the corneal stroma
0007759
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Percent of people who have these symptoms is not available through HPO
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Autosomal recessive inheritance
0000007
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum

[ more ]

0001321
Decreased liver function
Liver dysfunction
0001410
Elevated hepatic transaminase
High liver enzymes
0002910
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Global developmental delay
0001263
Hepatomegaly
Enlarged liver
0002240
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Increased CSF protein
0002922
Intellectual disability, profound
IQ less than 20
0002187
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952
Long philtrum
0000343
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Microretrognathia
Small retruded chin
0000308
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Pachygyria
Fewer and broader ridges in brain
0001302
Petechiae
0000967
Polymicrogyria
More grooves in brain
0002126
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
Splenomegaly
Increased spleen size
0001744
Thrombocytopenia
Low platelet count
0001873
Ventriculomegaly
0002119

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.