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Disease Profile

Acrocallosal syndrome, Schinzel type

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

Q04.0

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)

Schinzel syndrome 1; Acrocallosal syndrome; ACS;

Categories

Congenital and Genetic Diseases; Musculoskeletal 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: 36

Definition
A polymalformative syndrome characterized by agenesis of corpus callosum (CC), distal anomalies of limbs, minor craniofacial anomalies and intellectual deficit.

Epidemiology
The prevalence is not known but fewer than 50 cases of ACS have been published since the first description in 1979.

Clinical description
In ACS, craniofacial anomalies include macrocephaly with protruding forehead and occiput, hypertelorism, large anterior fontanel, short mandible and nose with anteverted nostrils and broad nasal bridge. Cases of anencephaly were observed, as well as, in other infants, an extra bone within the anterior fontanel, a calvarian defect or a Dandy-Walker malformation (see this term). CC hypoplasia or agenesis is the main distinctive feature of ACS. It may be associated with arachnoidal cysts in about one third of cases and with various other brain abnormalities (medulla oblongata, temporal lobe or pons hypoplasia, micropolygyria and hypoplasia or agenesis of cerebellar vermis). Distal anomalies of limbs include preaxial or postaxial polydactyly or polysyndactyly of toes and/or hands. The large majority of ACS patients have intellectual deficit that is severe in 80% of cases, and substantial psychomotor retardation. Additional malformations have been described occasionally: short philtrum/upper lip, high-arched palate, cleft lip/palate, heart defects, hypospadias and inguinal and umbilical hernias.

Etiology
Mutations of the kinesin KIF7 (15q26.1) and the transcriptional activator GLI3 (7p14.1) genes are responsible for ACS. Both genes are involved in the ciliary Sonic Hedgehog pathway and their mutation most likely influences the early development of midline structures during embryogenesis.

Diagnostic methods
Diagnosis is based on physical examination and, given the high variability of phenotypes, a consensus on minimal diagnostic criteria has been established, with 3 of the 4 following criteria being necessary to suspect the ACS diagnosis: (1) total or partial absence of the CC, (2) minor craniofacial anomalies, (3) moderate to severe psychomotor retardation with hypotonia and (4) polydactyly.

Differential diagnosis
Differential diagnosis includes Greig cephalopolysyndactyly, oral-facial-digital I and II, Meckel-Gruber, Smith-Lemli-Opitz, Rubinstein-Taybi, cerebrooculofacioskeletal, Aicardi, Neu-Laxova, pseudotrisomy 13, Toriello-Carey, otopalatodigital II and Da Silva syndromes (see these terms).

Antenatal diagnosis
Antenatal diagnosis is based on ultrasonography examination from the 20th week of gestation and magnetic resonance imaging (MRI) of the fetus.

Genetic counseling
ACS is an autosomal recessive disease. There is therefore a 25% recurrence risk for a subsequent pregnancy. If the gene mutation in the kinesin/transcriptional activator genes has been identified in an affected sibling, molecular genetic diagnosis can be offered after chorionic villus sampling.

Management and treatment
Surgical intervention may be considered for the polydactyly.

Prognosis
Prognosis depends on the severity of malformations and hypotonia, and on the occurrence of seizures.

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
100% of people have these symptoms
Aplasia/Hypoplasia of the corpus callosum
0007370
80%-99% of people have these symptoms
Duplication of phalanx of hallux
Duplication of big toe bone
Duplication of great toes

[ more ]

0010066
Duplication of thumb phalanx
0009942
Hypertelorism
Widely spaced eyes
Wide-set eyes

[ more ]

0000316
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Macrocephaly
Increased size of skull
Large head circumference
Large head

[ more ]

0000256
Postaxial foot polydactyly
Extra toe attached near the little toe
0001830
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

0001162
Preaxial foot polydactyly
0001841
Preaxial hand polydactyly
Extra thumb
0001177
30%-79% of people have these symptoms
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

0000337
Dandy-Walker malformation
0001305
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Finger syndactyly
0006101
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Inguinal hernia
0000023
Preauricular skin tag
0000384
Prominent occiput
Prominent back of the skull
Prominent posterior skull

[ more ]

0000269
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770
Triphalangeal thumb
Finger-like thumb
0001199
Umbilical hernia
0001537
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
5%-29% of people have these symptoms
Abnormal clavicle morphology
Abnormal collarbone
0000889
Aplasia/Hypoplasia of the cerebellum
Absent/small cerebellum
Absent/underdeveloped cerebellum

[ more ]

0007360
Coloboma
Notched pupil
0000589
Congenital diaphragmatic hernia
0000776
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypospadias
0000047
Micropenis
Short penis
Small penis

[ more ]

0000054
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Sensorineural hearing impairment
0000407
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Tall stature
Increased body height
0000098
Tapered finger
Tapered fingertips
Tapering fingers

[ more ]

0001182
1%-4% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears

[ more ]

0000377
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Frontal bossing
0002007
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Hypoplasia of teeth
0000685
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Intracranial cystic lesion
0010576
Long philtrum
0000343
Microretrognathia
Small retruded chin
0000308
Open mouth
Gaped jawed appearance
Gaped mouthed appearance
Slack jawed appearance

[ more ]

0000194
Seizure
0001250
Short philtrum

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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

      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 Acrocallosal syndrome, Schinzel type. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        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 Acrocallosal syndrome, Schinzel type. Click on the link to view a sample search on this topic.

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