Zimmermann–Laband Syndrome

Overview

Zimmermann–Laband syndrome (ZLS) is a rare genetic disorder characterized by a combination of craniofacial abnormalities, gingival fibromatosis (excessive gum overgrowth), skeletal anomalies, and intellectual disability. The syndrome was first described by Zimmermann in 1928 and further defined by Laband in the 1960s. It belongs to a group of disorders involving connective tissue development and has two known subtypes (ZLS1 and ZLS2), each linked to different genetic mutations. Due to its rarity, fewer than 100 cases have been reported in medical literature.

Causes

ZLS is primarily caused by mutations in one of two genes:

• KCNH1 – associated with Zimmermann–Laband syndrome type 1 (ZLS1)

• ATP6V1B2 – associated with Zimmermann–Laband syndrome type 2 (ZLS2)

These genes are involved in regulating ion channels and cellular transport mechanisms. The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is sufficient to cause the disorder. In many cases, however, the mutation arises de novo (sporadically), with no prior family history.

Symptoms

Zimmermann–Laband syndrome presents with a broad range of physical and developmental abnormalities. Common symptoms include:

• Gingival fibromatosis – thick, overgrown gums, often requiring surgical reduction

• Coarse facial features – bulbous soft nose, thick lips, and large ears

• Hepatomegaly and/or splenomegaly in some cases

• Skeletal anomalies – hyperextensible joints, long and thin fingers (arachnodactyly), and hypoplasia of the distal phalanges

• Developmental delay and mild to moderate intellectual disability

• Enlarged nails or nail dysplasia

• Occasional epilepsy or behavioral disturbances

Severity and specific manifestations can vary between individuals, even within the same family.

Diagnosis

Diagnosis is based on clinical features and confirmed with genetic testing. Diagnostic steps may include:

• Thorough physical examination to identify characteristic facial and skeletal features

• Dental evaluation for gingival fibromatosis

• Radiographic imaging of hands and long bones to assess phalangeal abnormalities

• Developmental and cognitive assessments

• Genetic testing to identify mutations in KCNH1 or ATP6V1B2

Because ZLS shares features with other overgrowth or craniofacial syndromes, differential diagnosis is important to exclude conditions like Coffin–Siris syndrome or gingival fibromatosis with hypertrichosis.

Treatment

There is no cure for Zimmermann–Laband syndrome. Treatment focuses on managing the symptoms and improving quality of life. Common approaches include:

• Regular dental care and gingivectomy procedures to manage gum overgrowth

• Speech, occupational, and physical therapy for developmental support

• Orthopedic interventions for joint and skeletal issues

• Special education services for learning difficulties

• Behavioral therapy and anticonvulsants if seizures or behavioral symptoms occur

A coordinated, multidisciplinary care team is often needed to address the various manifestations over time.

Prognosis

Zimmermann–Laband syndrome is a lifelong condition, but it is not considered life-threatening. The prognosis depends on the severity of physical and intellectual impairments. Many individuals live into adulthood and can function independently with supportive care. However, developmental and behavioral challenges may limit academic and occupational achievements. Early intervention and personalized therapy significantly improve long-term outcomes.