What Is Acrocallosal Syndrome - Schinzel Type?


Acrocallosal syndrome - Schinzel Type, also known as ACLS, is a rare and complex genetic disorder that is apparent at birth (congenital), and it affects various aspects of the infant’s development.¹ ² This article provides a thorough exploration of ACLS, its clinical features, diagnosis, treatment options, prognosis, and ongoing research efforts. Hopefully, this information increases awareness and understanding of this condition and its impacts on both individuals and their families.

Overview of acrocallosal syndrome³

Acrocallosal syndrome - Schinzel Type, originally reported in 1979 by A. Schinzel, is a rare genetic disorder typically characterised by a combination of physical, craniofacial, and neurological abnormalities. 

Research suggests this condition is likely to be a recessive autosomal disease, meaning that the person only inherits the condition if each of the parents passes on the faulty gene, causing their offspring to have two copies of the faulty gene. 

Some investigators have found that ACLS is a result of mutations in the kinesin (motor protein)⁴ KIF7 and sometimes in the transcriptional activator (a protein that turns on genes to copy genetic material)⁵ GLI3. Both these genes are involved in the development of the midline structures of the brain, the structures that connect the two hemispheres of the brain, and therefore, a mutation in these genes will likely affect their subsequent development.

ACLS is an exceedingly rare genetic disorder with only a limited number of cases reported worldwide. Due to its rarity, accurate prevalence data is challenging to obtain, but fewer than 50 cases have been published since its first report in 1979.

Clinical features of ACLS

The range and severity of the associated signs and symptoms vary widely in individuals with ACLS. However, in all reported cases, the disorder has been characterised by the underdevelopment (hypoplasia) or absence (agenesis) of the thick band of nerve fibres joining the two hemispheres of the brain known as the corpus callosum, as well as moderate to severe mental retardation. Furthermore, in some cases, brain malformations may cause additional complications such as seizures or hydrocephalus (the impaired flow or absorption of cerebrospinal fluid, leading to an increase in the fluid pressure in the brain). Individuals with ACLS may also have diminished muscle tone (hypotonia) and experience severe psychomotor retardation or marked delays in some developmental milestones.  

Additionally, many of the affected individuals have skull and facial (craniofacial) region malformations and/or distinctive abnormalities of the fingers and toes. Frequent characteristic craniofacial abnormalities may include:

  • Unusually large head (macrocephaly) with a prominent forehead
  • Widely spaced eyes (ocular hypertelorism)Downslanting eyelid folds (palpebral fissures)
  • A small nose with a broad nasal bridge
  • Upwardly turned nostrils (anteverted nares
  • Malformed (dysplastic) ears that may be abnormally rotated toward the back of the head
  • A prominent back region of the head (occiput)
  • Underdeveloped midfacial regions (midfacial hypoplasia)
  • Potential abnormally large “soft spot” at the front of the skull. These are membrane-covered gaps between the bones of the skull at birth
  • Occasionally have protruding lips, an abnormal groove in the upper lip (cleft lip), and/or incomplete closure of the roof of the mouth (cleft palate)Also, most affected individuals have distinctive digital malformations; these include:
    • Presence of extra (supernumerary) fingers and toes (polydactyly)
    • The webbing or fusion (syndactyly) of certain digits

Additional physical abnormalities may also occur; these include growth retardation, structural heart malformations such as a hole in the septum or of the valves, epigastric hernias or protrusion of an internal organ through the membrane of the middle region of the abdomen. Moreover, some affected males may have genitalia abnormalities such as undescended testes (cryptorchidism), abnormal placement of urinary openings (hypospadias), and/or an unusually small penis (micropenis).

For some infants with ACLS,some complications may be present shortly after birth including of seizures, feeding difficulties, and an increased risk of respiratory infections. In some cases, respiratory infections as well as breathing difficulties (dyspnea), lack of sufficient oxygen supply to bodily tissues (hypoxia), and other associated abnormalities (i.e., respiratory distress) may lead to potentially life-threatening complications.

However, as mentioned previously, reports in the medical literature suggest that the symptoms and findings associated with acrocallosal syndrome, Schinzel type may vary greatly in range and severity from case to case.


For families that have members who have been previously diagnosed with acrocallosal syndrome Schinzel type, it might be suspected prenatally and tested using specialised tests such as ultrasound or foetoscopy. In a foetoscopy, a flexible, ultrasound-guided viewing instrument is introduced into the uterus through the abdominal wall to directly observe the foetus.

However, the diagnosis is only usually made or confirmed at birth following a thorough clinical evaluation, identification of the characteristic physical symptoms, and various specialised tests such as genetic testing, CT and MRI scans, as well as a cardiac evaluation.

Treatment and management

The treatment of ACLS is based on the specific symptoms that each individual presents. As a result, the management of ACLS requires a multidisciplinary team of healthcare professionals, including paediatricians, surgeons, neurologists, cardiologists, and orthopedists. This collaborative and patient-centred approach is essential for addressing the diverse range of symptoms and challenges associated with the syndrome.

Each treatment recommended will be in response to their corresponding symptom. For example, for those with hydrocephalus early surgery might be advised to insert a shunt (tube) to drain excess cerebrospinal fluidinto another part of the body to be absorbed and decrease fluid pressure in the brain. Another example is surgery to correct certain craniofacial malformations, polydactyly and syndactyly, and/or other physical abnormalities potentially associated with the disorder.  

Additionally, for those with congenital heart defects, treatment with certain medications, surgical intervention, and other measures may be necessary. The surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.

Moreover, physicians may regularly monitor affected infants and children to help ensure prompt detection and early treatment of respiratory infections.

To manage the disease, supportive therapies may also be included to ensure proper caloric intake and nutrition and to prescribe the required medications to manage other symptoms, such as the usage of anticonvulsants to cope with seizures.

Regardless of the severity and the symptoms presented by the infant, it is fundamental to have an early intervention in order to better help them treat and manage their conditions and improve their quality of life.

Prognosis and life expectancy

The prognosis of individuals with ACLS varies widely depending on the severity of their symptoms and the availability of early intervention and support. This leads some individuals to experience a shorter life expectancy and poorer quality of life whilst others have a more typical one.

Coping and support for patients and families

A diagnosis of ACLS can be emotionally challenging for not only the affected individual but also for their families. Access to counselling and support services may be essential to help families cope with the psychological and emotional aspects associated with the condition.

Support groups go above psychological support by also providing families with information and opportunities to connect with other families facing similar challenges, building a sense of community.

These are two support groups in the UK that help with conditions related to the agenesis (absence) of the corpus callosum:

For organisations in the US, here is a link with the list of support groups: https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=nord22 

Ongoing research and future directions

Ongoing research endeavours aim to deepen further our understanding of the acrocallosal syndrome, Schinzel type, as well as develop new therapies and interventions to improve the impact of the symptoms and, subsequently, their quality of life.


Acrocallosal Syndrome - Schinzel Type (ACLS) is a rare genetic disorder characterised by craniofacial abnormalities, limb malformations, and central nervous system issues. While ACLS is exceptionally rare, its impact on affected individuals is significant. Diagnosis often involves genetic testing, and treatment requires a multidisciplinary approach, including surgeries and various therapies. The prognosis varies but can be improved with early interventions and support. Due to the challenging nature of ACLS, families and the affected individuals would benefit from psychological support, support groups, and reliable resources. However, on a hopeful note, ongoing research that aims to understand ACLS better, potentially leading to targeted treatments and improved outcomes provides an optimistic prospect.


  1. Acrocallosal syndrome: MedlinePlus Genetics [Internet]. medlineplus.gov. Available from: https://medlineplus.gov/genetics/condition/acrocallosal-syndrome/
  2. Acrocallosal Syndrome, Schinzel Type [Internet]. NORD (National Organization for Rare Disorders). Available from: https://rarediseases.org/rare-diseases/acrocallosal-syndrome-schinzel-type/
  3. RESERVED IU -- AR. Orphanet: Acrocallosal syndrome [Internet]. www.orpha.net. [cited 2023 Sep 8]. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=36
  4. Kinesin - an overview | ScienceDirect Topics [Internet]. www.sciencedirect.com. Available from: https://www.sciencedirect.com/topics/neuroscience/kinesin
  5. Ma J. Transcriptional activators and activation mechanisms. Protein & Cell. 2011 Nov;2(11):879–88.
  6. Acrocallosal Syndrome, Schinzel Type [Internet]. NORD (National Organization for Rare Disorders). Available from: https://rarediseases.org/rare-diseases/acrocallosal-syndrome-schinzel-type/
  7. Acrocallosal Syndrome - an overview | ScienceDirect Topics [Internet]. www.sciencedirect.com. [cited 2023 Sep 9]. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/acrocallosal-syndrome
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Érica Ramos Lopes Sousa

Medical Undergraduate - MBBS / BSc , Imperial College London

Érica, a first-year medical student at Imperial College London, is already displaying a keen interest in the fields of neurosurgery and genetics. Her foundation in academic writing, acquired during her International Baccalaureate studies, serves as a strong platform for her goal of crafting informative health-related articles for the general public. As she progresses through her medical education, she harbours ambitions of further enhancing her expertise and insights, with the ultimate aim of contributing to significant advancements in the field of medicine.

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