Bachmann-Bupp syndrome is a type of developmental delay. It has been observed as an impairment of neurological development, no hair growth, dysmorphic differences, behavioural abnormalities, and feeding difficulties. It is a highly rare condition that only 9 individuals have been recorded in the literature data. Even though it is a newly discovered genetic condition, the fascinating collaboration with other research groups has already discovered a promising match with a repurposed anticancer drug. This drug is under investigation and waiting for FDA approval for its Bachmann-Bpp syndrome use.
What is bachmann-bupp syndrome?
Bachmann-Bupp syndrome (BABS) is a highly rare developmental impairment disorder.1 Only 9 individuals have written reports which indicate that they have been diagnosed with the syndrome from nine independent families across the whole globe. In addition to this, 3 more individuals have also been mentioned in the literature by the researchers without any medical reports. BABS is defined by a few characteristics, such as a type of alopecia, mild to intense levels of developmental setback, unspecific morphological abnormalities, hypotonia, behavioural problems and eating problems.
Alopecia is a medical condition where your own immune system attacks your hair follicles because of seeing it as a pathogen due to problems in identifying the body's own cells.2 Therefore, the hair falls out in clusters. For some patients, hair has been observed to present at bare intervals at birth and recorded to fall out later. Behavioural anomalies include autism spectrum disorder and attention-deficit disorder.1 Hypotonia is a condition where your muscles stay contracted even without moving, and you always feel tension.3
What causes bachmann-bupp syndrome?
Bachmann-Bupp syndrome is a genetic condition. It occurs as a result of the mutations in the gene that codes for Ornithine decarboxylase 1 (ODC1). This gene normally plays a significant role in organogenesis and embryogenesis, which are organ formation and embryo development processes, respectively, and neuronal cell growth. When the gene is mutated, it results in the formation of proteins with altered functions. Those proteins affect normal development and prevent the normal formation of the systems, and the characteristics mentioned above arise.4
Is bachmann-bupp syndrome heritable?
No, the information that has been obtained from the research so far suggests that the disease did not pass from the healthy parents. This means it is not transferable from one generation to the next. The mutations are believed to arise while the embryo develops. This means that healthy parents have not inherited the disease. However, there will be a chance of those individuals with Bachmann-Bupp syndrome to have a 50% chance of having a child with Bachmann-Bupp syndrome. Nevertheless, this information is not proven yet since the Bachmann-Bopp syndrome patients are not at their reproductive age yet.1
What are the symptoms and clinical features of bachmann-bopp syndrome?
The most remarkable characteristic of BABS is the alopecia syndrome. However, there is a long list of symptoms and clinical features accompanied by BABS disease.1 Here are the main highlights of the characteristics:
- Unspecified appearance anomalies
- Intellectual retardness
- Issues with feeding and intestines
- Brain abnormalities
- Issues on skin
- Hearing loss
- Heart disease
- Nail problems
The babies have been reported to have motor (movement) and speech delays compared to normal time slots. The head skull is larger compared to individuals without the condition. Besides, some babies were born with macrosomia, where the size or weight of the baby is larger than normal.
The behaviours of the individuals with BABS led to the diagnosis of Attention-deficit/hyperactivity disorder (ADHD), autism, and aggression conditions.
Some people are not able to eat by mouth, and they require a gastrointestinal feeding tube where they feed directly into their intestines. Meanwhile, some patients experience constipation.
The brain images of individuals with BABS are different from those of other individuals without the condition. The white matter, where the nerve fibres are located for the signal transduction between different parts of the brain, either gets lost or displays a change in behaviour. Moreover, lesions can also be observed in the brains of BABS patients.
Cysts can also be seen on the skin,, and dry skin was also monitored during childhood. Moreover, nails can be brittle or extra elastic.
How to diagnose bachmann-bpp syndrome?
The disease can be identified from the distinctive qualities mentioned above. There will be confusion with other genetic conditions due to carrying similarities with other disorders. As a result, the complete diagnosis can be achieved by molecular genetic testing with a method called whole exome sequencing (WES).5 This method simply scans the DNA for its exomes which are the regions that carry a code for protein production. In this case, they look for different variants of (ODC1) gene mutations mentioned above.
The management approach for the bachmann-bupp syndrome
The disease is very rare, with multiple conditions. Hence, a multidisciplinary approach is required to manage the disease. The geneticist and neurologists can co-work at the diagnosis stage and identify how many of the characteristics are present and how severe the condition is. Therapists can work together for speech therapy for talking delay and physical therapy for motor skills. For the cognitive challenges related to cognitive functions, educational support will be delivered by the teachers. On the other hand, counselling support for the families is also highly beneficial for emotional strength and better coping up with the situation. It is very important to start those therapies as early as possible to improve the quality of life and develop abilities while growing up.
How to treat bachmann-bupp syndrome?
The drug α-difluoromethylornithine (DFMO) is a type of drug which is approved by the US Food and Drug Administration (FDA) for anti-cancer treatment and is currently in use for the clinical setting for the treatment of BABS patients 6. However, the drug is still under investigation for BABs patients, and it has not been approved by the FDA for its new purpose. DFMO is also known as eflornithine.
There are promising results from the clinical evaluation of the DFMO. The positive outcome of the treatment includes the growth of eyebrow and scalp hair, being able to sit without assistance, and gaining limited motor skills, such as holding a fork for feeding alone. Also, follicular cysts on the skin did not re-occur on the patient's skin after the treatment.6 Furthermore, there are outcomes from different research groups that indicated the observation of weight gain, healthier posture, and other neurological improvements.
Additionally, feeding tubes are used for eating problems, stool smoothing or osmotic agents are in use for constipation problems, and the application of standard treatments for mental disorders is also accompanied by the DFMO treatment of BABs patients.
Moreover, the therapies used for other conditions which have been mentioned above are also in use due to already proven effectiveness and safety for the disorders by the research.
What is the prognosis of the disease?
It is hard to comment on the prognosis of Bachmann-Bupp syndrome with only 9 patients with literature data. However, it can be proposed that the prognosis is very similar for all patients except for a few additional diagnoses for some patients. The severity of the disease is mostly the same with differences in motor activity levels4 as long as the patients do not have seizures, which increase the intensity of the condition. To further clarify the differences, some patients have seizures and are non-mobile whereas some patients have vision and nail differences. However, the individuals with slightly different characteristics were treated with the same DFMO drug, and all have already displayed improvement in their symptoms.5
Meanwhile, there is no evidence about the life expectancy of the patients. In the past, the condition was unknown. The individuals have not grown up yet.
Is there any current research on the bachmann-bupp syndrome?
Currently, Difluoromethylornithine (DFMO) is under investigation and waiting for FDA approval for its use in the Bachmann-bupp syndrome. DFMO analogues are also under research. Those analogues have the same typical shape as DFMO but have different chemical structures.1 Additionally, OCD gene inhibitors, which are a type of drug that blocks the activity of the mutated gene OCD mentioned above, are also being evaluated.
However, the research and treatment are highly challenging for the rare disease due to having a very small number of patients with the disease, the high cost of clinical trials and drug development, as well as limited availability of the information.
Bachmann-bupp syndrome includes a metabolic dysfunction within the same pathway as other diseases, and the OCD gene has already been investigated.6 Consequently, finding a suitable drug and further investigating it was easy, gladly.
Summary of key points
- Bachmann-bupp syndrome is a highly rare genetic disorder
- Only 9 individuals with a medical record are known who carry the disorder
- The onset of the disease is similar for all
- Few of them had seizures, which made the condition severe.
- Bachmann-bupp syndrome is a recently discovered condition
- The anti-cancer drug DFMO is under investigation for Bachmann-bupp
- Therapy in many forms can help patients live better lives
- Early detection of anomalies is important
- Cognitive dysfunction and speech difficulties can be elevated
- Neurological improvements have been achieved with DFMO
- More research is required to understand the prognosis of the disease
- The life expectancy of Bachmann-bupp syndrome patients is unknown
- More information is required for better understanding of the disease
- Bupp C, Michael J, VanSickle E, Rajasekaran S, Bachmann AS. Bachmann-Bupp Syndrome [Internet]. Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. PubMed. Seattle (WA): University of Washington, Seattle; 1993 [cited 2023 Aug 23]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK583220/
- Darwin E, Hirt P, Fertig R, Doliner B, Delcanto G, Jimenez J. Alopecia areata: Review of epidemiology, clinical features, pathogenesis, and new treatment options. International Journal of Trichology [Internet]. 2018;10(2):51. Available from: http://www.ijtrichology.com/article.asp?issn=0974-7753;year=2018;volume=10;issue=2;spage=51;epage=60;aulast=Darwin;type=3
- Madhok SS, Shabbir N. Hypotonia [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562209/
- VanSickle E, Michael J, Bachmann AS, Rajasekaran S, Prokop JW, Kuzniecky R, et al. Expanding the phenotype: Four new cases and hope for treatment in Bachmann‐Bupp syndrome. American Journal of Medical Genetics. 2021 Sep 3;185(11):3485–93.
- Rajasekaran S, Bupp CP, Leimanis-Laurens M, Shukla A, Russell C, Junewick J, et al. Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease. eLife. 2021 Jul 20;10.
- Bachmann AS, VanSickle E, Michael J, Vipond M, Bupp C. Bachmann–Bupp syndrome and treatment. Developmental Medicine & Child Neurology. 2023 Jul 19;