Bachmann-Bupp Syndrome

Excerpt

Clinical characteristics: Bachmann-Bupp syndrome (BABS) is characterized by a distinctive type of alopecia, global developmental delay in the moderate to severe range, hypotonia, nonspecific dysmorphic features, behavioral abnormalities (autism spectrum disorder, attention-deficit/hyperactivity disorder) and feeding difficulties. Hair is typically present at birth but may be sparse and of an unexpected color with subsequent loss of hair in large clumps within the first few weeks of life. Rare findings may include seizures with onset in later childhood and conductive hearing loss.

Diagnosis/testing: The finding of abnormal polyamine pathway metabolites (including increased N-acetylputrescine) on metabolomic profiling is suggestive of a diagnosis of BABS. The diagnosis is established in a proband with suggestive findings and a heterozygous pathogenic variant in ODC1 identified by molecular genetic testing. Heterozygous pathogenic variants in ODC1 that cause BABS are typically gain-of-function variants.

Management: Treatment of manifestations: Feeding therapy with a low threshold for a clinical feeding evaluation and/or gastrostomy tube placement; nutritional intervention for those with obesity; stool softeners, prokinetics, osmotic agents or laxatives for constipation; standard treatment for epilepsy, developmental delay / intellectual disability, refractive error, strabismus, hearing loss, follicular cysts, and congenital heart defects.

Surveillance: Measurement of growth parameters, evaluation of nutritional status and safety of oral intake, monitoring for signs and symptoms of constipation, assessment of mobility and self-help skills, monitoring of developmental progress and educational needs, and assessment for new manifestations (seizures, changes in tone) at each visit. Complete skin evaluation for follicular cysts at least annually. Behavioral assessment for signs of autism spectrum disorder, attention, and aggressive or self-injurious behaviors annually. Ophthalmology and audiology evaluations annually or as clinically indicated.

Therapies under investigation: An experimental targeted treatment with difluoromethylornithine (DFMO) is being explored on a compassionate use basis; it is not currently an FDA-approved treatment for BABS.

Genetic counseling: BABS is expressed in an autosomal dominant manner and typically caused by a de novo ODC1 pathogenic variant. Therefore, the risk to other family members is presumed to be low. Once an ODC1 pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.