Zimmermann–Laband Syndrome (ZLS)

Zimmermann–Laband syndrome (ZLS) is an extremely rare autosomal dominant congenital disorder characterized by a combination of distinctive facial features, abnormalities of the fingers and toes, and other developmental and health issues. The term was coined by Carl Jacob Witkop in 1971.

Symptoms & Signs:

• Facial Features: Individuals with ZLS often have coarse facial features, including a broad nasal bridge, wide nostrils, thick lips, and large, low-set ears. The eyebrows may be bushy, and the eyelashes may be long and thick.
• Gingival Hypertrophy: One of the hallmark features of ZLS is gingival hypertrophy, which refers to overgrowth of the gums. This can lead to enlarged, thickened gums that may cover the teeth and cause dental problems.
• Skeletal Abnormalities: ZLS can involve abnormalities of the bones and joints, particularly in the fingers and toes. These abnormalities may include extra fingers or toes (polydactyly), unusually shaped nails, and joint stiffness or contractures.
• Developmental Delay: Some individuals with ZLS may experience developmental delay, including delays in reaching developmental milestones such as sitting, standing, and walking. Intellectual disability may also be present in some cases.

Zimmermann-Laband syndrome is caused by mutations in the gene encoding the ATPase family AAA domain-containing protein 5 (ATAD5). This gene is involved in various cellular processes, including DNA repair and cell cycle regulation. The inheritance pattern of ZLS is typically autosomal dominant, meaning that a mutation in one copy of the ATAD5 gene is sufficient to cause the disorder. Type 1 ZLS is caused by pathogenic variants (mutations) in a potassium channel gene – KCNH1. Similar pathogenic variants in this gene were previously found to cause Temple-Baraitser syndrome, which shares similar clinical features. This has led many to believe that ZLS, type 1 and TBS are actually the same disorder. Type 2 ZLS is caused by pathogenic variants in the brain isoform of V-type proton ATPase subunit B, ATP6V1B2.

Management:

Management of Zimmermann-Laband syndrome typically involves a multidisciplinary approach to address the various symptoms and complications associated with the disorder. This may include dental care to manage gingival hypertrophy, physical therapy to address skeletal abnormalities and joint stiffness, and educational support for developmental delay and intellectual disability. Genetic counseling may also be beneficial for affected individuals and their families to understand the inheritance pattern of the syndrome and the risk of passing it on to future generations.