Clinical Guidance

LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurologic disorder of central nervous system white matter. Adults show autonomic dysfunction, the first evidence of the disorder, in the fourth to fifth decade of life, followed by pyramidal and cerebellar abnormalities resulting in spasticity, ataxia, and tremor . To date, at least 33 families have been identified with a pathogenic variant in LMNB1 [, , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Autonomic dysfunction, a nearly universal feature , includes bladder dysfunction, constipation, postural hypotension, erectile dysfunction, and (less often) impaired sweating.

Diagnostic Criteria

No formal diagnostic criteria exist.

Suggestive Findings

LMNB1-related autosomal dominant leukodystrophy (ADLD) should be suspected in adults with the following clinical, neuroimaging, and family history findings:

Clinical features

• Onset in the fourth to fifth decade of signs and symptoms of autonomic dysfunction including bladder dysfunction, constipation, erectile dysfunction, and postural hypotension

Management Guidelines

No clinical practice guidelines for LMNB1-related autosomal dominant leukodystrophy (ADLD) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with LMNB1-related ADLD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with LMNB1-related Autosomal Dominant Leukodystrophy (ADLD)

Surveillance Guidelines

Recommended surveillance:

• Routine assessment of weight, nutrition, and feeding; pulmonary status (re possible recurrent pneumonia); bladder and erectile function; psychosocial well-being; and medications and dosage to avoid iatrogenic polypharmacy

• At least annual assessment by multidisciplinary specialists including a neurologist for disease manifestations and progression; and by a physiatrist, orthopedist, physical therapist, and occupational therapist to address orthopedic, equipment, and functional needs