Introduction 

Bachmann-Bupp syndrome (BABS) is a rare genetic disorder characterised by a range of developmental and neurological symptoms. Patients affected by BABS may exhibit developmental delays, intellectual disabilities, speech and language difficulties, behavioural abnormalities, such as autism spectrum disorder, and hypotonia.¹ 

BABS expression occurs in an autosomal dominant manner, in which pathogenic variants or mutations in the ornithine decarboxylase (OCD1) gene lead to elevated retention of the OCD protein. The decarboxylase converts ornithine into putrescine, and as there are increased OCD levels, this leads to enhanced cellular accumulation of putrescine.² Although putrescine is an important component for cell growth in mammals,³ excess levels of putrescine are associated with cell membrane damage⁴ and necrotic cell death.⁵ 

Early intervention is crucial in managing BABS as it may significantly improve the quality of life for affected individuals. By identifying and addressing the symptoms early through targeted therapies and medical interventions, there is potential to mitigate the impact of the disorder on cognitive, motor, and social development. This article aims to address early intervention and therapies that provide families with the necessary tools and support to navigate the challenges associated with the syndrome.

Early identification of Bachmann-Bupp syndrome

BABS was first reported in the medical literature in 2018, and the prevalence of this rare disorder is unknown. In November 2022, there were fewer than 30 affected individuals worldwide, but the number of identifiable cases may have risen since.²

Bachmann-Bupp syndrome presents with a range of developmental and neurological symptoms, which may vary in severity among affected individuals. Early identification of these symptoms is crucial for timely intervention. Key symptoms and signs include:

• Alopecia
  • One of the main early identifiable features of BABS is a distinctive form of alopecia, in which the affected individual will typically have hair at birth but experiences sudden-onset hair loss¹ 
• Distinctly absent or sparse eyebrows and eyelashes² 
• Nonspecific dysmorphic features
  • Elongated heads and faint eyebrows⁶

• Moderate to severe developmental delays
  • Affected children often struggle with mobility issues, with some toddlers achieving to walk by the age of four, whilst others are hindered indefinitely
• Hypotonia
  • Hypotonia, reduced muscle tone, may contribute to motor delays and difficulties in movement 
•  Speech and language impairments
  • Some children may have severe speech delays or be non-verbal¹ 
• Feeding difficulties
• Seizures
• Behavioural and emotional symptoms
  • Autism-spectrum disorder-like features may be exhibited in some BABS-affected individuals, such as social communication difficulties.
  • Attention-deficit/hyperactivity disorder (ADHD)
  • Aggression
• Skin problems
  • Appearance of keratosis pilaris, recurrent follicular cysts and dry skin in childhood.
•  Macrocephaly² 

The diagnostic process for BABS involves a combination of clinical evaluation, genetic testing and additional diagnostic tools. Since many symptoms associated with BABS are also present in other disorders, there may be confusion in accurate diagnosis. Therefore, it is essential to pursue comprehensive and differential diagnosis via: 

• Collaboration with multidisciplinary specialists
  • To identify distinctive manifestations
• Molecular genetic testing for variants in the OCD1 gene
• Testing for biomarkers 

That being said, a consensus clinical diagnostic criteria for BABS is yet to be established.¹ 

Early intervention strategies

Early intervention and therapies for BABS focus on managing symptoms and preventing complications from arising. As mentioned previously, a multidisciplinary approach is necessary to manage the complexity of the condition. Since clinical features vary among affected individuals, the treatment of BABS is therefore tailored to the patient. The following are treatment options that may be recommended for BABS-affected individuals:

Medication

• Muscle-tone management - alpha-Difluoromethylornithine (DFMO) is a drug that inhibits ODC. DFMO is used to treat trypanosomiasis and many cancers, but may be repurposed to manage hypotonia symptoms in BABS. Affected individuals with BABS display improved muscle tone and hair growth after DFMO administration⁷
• Behavioural and mood regulation - in cases where behavioural issues such as hyperactivity, irritability, or mood disorders are present, medications used to treat ADHD and other behavioural concerns may be considered to help stabilise mood and manage symptoms¹
• Seizure management - a neurological evaluation may be performed on patients displaying seizure symptoms. The choice of medication depends on the type and frequency of seizures²

Surgical intervention

• Orthopaedic surgery - for individuals with significant motor impairments, such as contractures or scoliosis resulting from hypotonia or muscle imbalance, orthopaedic surgery might be necessary to improve mobility and prevent complications
• Gastrointestinal Surgery - in cases where feeding difficulties lead to significant nutritional deficits or aspiration risks, surgical interventions like gastrostomy tube placement might be necessary to ensure adequate nutrition²

Therapeutic approaches 

• Speech therapy - speech language specialists may perform an augmentative and alternative communication (AAC) evaluation on individuals who express language distress. Speech therapy is essential for addressing delays in speech and language development. Therapists work on building vocabulary, improving articulation, and developing expressive and receptive language skills
• Occupational therapy - this type of therapy helps individuals develop fine motor skills necessary for daily activities such as dressing, feeding, and writing. Therapists may use exercises and activities that enhance hand-eye coordination, dexterity, and strength
• Physical therapy - patients are recommended to undergo physical therapy to maximise mobility and improve gross motor skills. This may reduce the risk of further orthopaedic complications, such as scoliosis¹ 

Early and consistent implementation of these medical and therapeutic interventions can significantly enhance the quality of life and developmental outcomes for individuals with BABS. The goal is to maximise functional abilities, promote independence, and improve overall well-being.

Educational and developmental interventions

Educational and developmental interventions are critical components of a comprehensive approach to managing BABS. These interventions and consultation with paediatric specialists aim to support the child’s cognitive, social, and emotional development, helping them reach their full potential in both academic and everyday life.

Early childhood education is crucial for children with BABS, as it provides a structured environment where developmental milestones can be nurtured. Early intervention programs focus on promoting cognitive, language, motor, and social skills, all of which may be delayed in children with BABS. Early developmental programs are designed specifically for children with developmental delays and disabilities. They provide individualised attention and specialised instruction in a supportive setting.¹

Individualised education plan (IEP) services are available to all ages and outline the educational goals, accommodations, and services a child with BABS will receive in the school setting. The IEP is tailored to the specific needs of the child and is developed through a collaborative process involving educators, therapists, parents, and other specialists. The IEP process begins with a comprehensive assessment of the child’s strengths, challenges, and needs. Based on this assessment, specific, measurable goals are established in areas such as academic achievement, communication, social skills, and motor development. There is an annual review of the IEP to ensure appropriate decisions are made in the patient’s best interest.¹ 

Parents of children with BABS need to understand the disorder so that they can adapt their lifestyle to the betterment of their children. Educating parents on how to reinforce social skills at home is crucial. Parents can be trained to use strategies that encourage positive social interactions in everyday situations. Participation in community programs, such as sports, arts, or recreational activities, provides additional opportunities for children with BABS to practise social skills and interact with a broader peer group in a supportive environment.²

These educational and developmental interventions are designed to support the holistic development of children with BABS, helping them to achieve their academic potential, build meaningful social relationships, and develop the skills needed for daily life.

Summary 

BABS is a rare genetic disorder caused by mutations in the OCD1 gene, leading to developmental delays, neurological symptoms, and other systemic effects. Early identification and intervention are critical for improving outcomes and managing the wide range of symptoms associated with this condition. Due to the similarity of symptoms between BABS and other developmental or neurological disorders, accurate diagnosis can be challenging. Comprehensive genetic testing, differential diagnosis, and collaboration with a multidisciplinary team are essential to ensure a correct diagnosis and to tailor appropriate interventions. By addressing the unique needs of each individual with BABS, these interventions aim to maximise their developmental potential, enhance their quality of life, and support their long-term well-being.