Bachmann-Bupp Syndrome

Bachmann-Bupp syndrome (BABS) is a rare genetic disorder caused by gain-of-function changes (pathogenic variants or mutations) in the ODC1 gene. Affected individuals have a distinctive type of hair loss (alopecia), global developmental delay, low muscle tone (hypotonia), nonspecific abnormal physical characteristics (dysmorphic features) and behavioral abnormalities. There is no cure for the disorder, but research is underway to better understand and treat this disease. Current treatment is aimed at the specific symptoms present in each individual.

• ODC1 gain-of-function-related neurodevelopmental disorder
• neurodevelopmental disorder with alopecia and brain abnormalities; NEDABA
• BABS

Causes

BABS is caused by changes (pathogenic variants or mutations) in the ornithine decarboxylase (ODC1) gene that are located at one end of the gene, the C terminus. Genes provide instructions for creating proteins which play a critical role in many bodily functions. Pathogenic variants in the ODC1 gene that cause BABS result in an elevated level of ODC protein followed by an increased conversion of ornithine to putrescine and increased accumulation of putrescine in the cells. These are called gain-of-function pathogenic variants.

The penetrance of pathogenic variants in the ODC1 gene is believed to be 100%, meaning that any person who has a pathogenic change in one copy of their ODC1 gene is expected to develop the associated signs and symptoms. It is unclear whether variations in different portions of the gene or variants resulting in loss-of-function of specific proteins may cause other symptoms.

BABS is inherited in an autosomal dominant pattern. Genetic conditions inherited in a dominant pattern occur when an individual has a pathogenic variant in one of their copies of a particular gene. Thus far, all reported patients whose parents have undergone molecular genetic testing have BABS as the result of a de novo, or new pathogenic variant that was not inherited. Each child of an individual with BABS has a 50% chance of inheriting the ODC1 pathogenic variant. To date, no individuals with BABS have reproduced and many are not yet of reproductive age.

Symptoms

There are 9 patients reported in the medical literature with BABS. From their histories, pathogenic variants in the ODC1 gene are thought to be responsible for the following:

• Alopecia – hair is typically present at birth but is sometimes sparse and atypical in color; hair loss in clumps begins in the first few weeks of life; there is typically congenital absence or sparseness of eyebrows and eyelashes; some individuals regrow scalp hair that usually remains sparse.
• Dysmorphic features have been identified in most affected individuals but not with any specific pattern or consistency.
• Moderate to severe global developmental delay – walking was achieved between ages 17 months and 4 years and first words were said between ages 3 and 6 years. Some individuals have not yet achieved these milestones at the time of this report.
• Hypotonia
• Behavior concerns – attention-deficit/hyperactivity disorder, autism spectrum and aggression have all been reported.
• Skin findings – Dry, rough patches and bumps on skin (keratosis pilaris), recurrent follicular cysts and dry skin have been reported.
• Feeding concerns and constipation.
• Large head (macrocephaly) and nonspecific brain MRI findings.
• Too much amniotic fluid during pregnancy (prenatal polyhydramnios).

Other findings reported have been quite variable. One patient has been reported with a history of seizures starting at 14 years of age. One individual has been reported with congenital sensorineural hearing loss in one ear. Two individuals with congenital heart disease – one with mild pulmonary stenosis and the other with self-resolved ventricular septal defect – have been reported. Two individuals with brittle nails and one with underdeveloped (hypoplastic) toenails have been reported. One individual with an inward turned eye (esotropia), eyes that appear to be misaligned (pseudostrabismus) and a vision abnormality related to an overly curved cornea (myopic astigmatism) has been reported.

Due to the small number of identified cases, the young age of reported patients and recent discovery of the condition, there is much yet to learn about the natural history of the disease.

Diagnosis

A diagnosis of BABS is based upon identification of characteristic symptoms and molecular genetic testing that reveals a pathogenic variant in the ODC1 gene. Consensus clinical diagnostic criteria have not been established.

Other tests may be performed to assess specific symptoms. For example, if seizure activity is seen or suspected based on body shaking or staring spells, physicians may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and help to detect seizures. Several patients with BABS have had changes noted on brain MRI, but not with a recurrent pattern of abnormalities.

Treatment

Following initial diagnosis, there are a variety of recommended evaluations. Evaluation with a gastroenterology/nutrition/feeding therapy team helps to investigate aspiration risk, nutritional status and signs of constipation. Developmental assessment is important to determine if early intervention services are needed. Neuropsychiatric evaluation is done to screen for behavior concerns. Ophthalmologic and audiology referrals are done to evaluate for vision or hearing concerns. A referral to a dermatologist is indicated if follicular cysts are present. A referral to a cardiologist is indicated if a heart murmur is present. If there is a concern for seizures, a neurologic evaluation with consideration of EEG might be recommended.

The treatment of BABS is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Primary care physicians, geneticists, neurologists and other healthcare professionals may need to systematically and comprehensively plan treatment.

Genetic counseling is recommended for families who have a child with BABS.

Psychosocial support for the entire family is essential as well.

Individuals with BABS are recommended to receive the following surveillance at each visit:

• Measurement of growth parameters
• Evaluation of nutritional status and safety of eating by mouth
• Constipation monitoring
• Assessment of mobility and self-help skills
• Developmental progress and educational needs evaluation
• Monitoring for new neurologic manifestations such as seizures and changes in tone
• Assessment of family needs for support and care coordination

Additionally, annual behavioral assessments, ophthalmology and audiology evaluations and skin checks for follicular cysts are recommended.

Affected children may benefit from occupational, physical and speech therapy. Additional medical, social and/or vocational services including specialized learning programs may be necessary.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.