Inspired by a patient
Finsterer J, Wakil SM, Laccone F. Familial, long-term pollakisuria as initial manifestation of HSP4 due to the SPAST variant c.683-2A>C. J Clin Neurosci. 2019 Jun;64:4-5.
Hereditary spastic paraplegia type-IV (HSP4) is the most common of the autosomal-dominant HSPs. Though urinary dysfunction is a frequent phenotypic feature, long-term pollakisuria as the initial manifestation of HSP4 has not been reported.
The patient is a 56yo female with an uneventful history until age 46y, when she developed pollakisuria. After another 6y she developed a coordination disorder, recognized as difficulties with running and climbing stairs. Since 6 m prior to presentation, she recognized mild dysphagia. The further history was positive for strabismus, varicosity, hepatopathy, thiamin-deficiency, niacin-deficiency, lumbago, cutaneous borelliosis, abortive psoriasis, lumbar spondylosis, osteochondrosis L5/S1, and HLA-B27-positive rheumatoid arthritis. Clinical exam revealed mild weakness for left foot extension (M5-), a right subclonic patella tendon reflex, and mildly impaired left hook transition. Nerve conduction studies revealed subclinical polyneuropathy. Ophthalmologic investigations, and MRI of the brain and spinal cord were non-informative. Genetic work-up revealed the novel variant c.683-2A > C in the SPAST gene. The family history was positive for HSP in her mother and sister. Pure HSP4 was diagnosed.
Pure HSP4 may manifest at onset with year-long pollakisuria exclusively. HSP4 may take a mild course over years, allowing the patient to do sports and to practice a demanding job.
Parodi L, Rydning SL, Tallaksen C, Durr A. Spastic Paraplegia 4. 2003 Apr 17 [updated 2019 Jun 13]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from http://www.ncbi.nlm.nih.gov/books/NBK1160/
Spastic paraplegia 4 (SPG4; also known as SPAST-HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. Sphincter disturbances are very common. Onset is insidious, mostly in young adulthood, although symptoms may start as early as age one year and as late as age 76 years. Intrafamilial variation is considerable.
The diagnosis of SPAST-HSP is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in SPAST identified by molecular genetic testing.
Treatment of manifestations: Antispastic drugs for leg spasticity; anticholinergic antispasmodic drugs for urinary urgency; regular physiotherapy to stretch spastic muscles and prevent contractures. Consideration of botulinum toxin and intrathecal baclofen when oral drugs are ineffective and spasticity is severe and disabling. Urodynamic evaluation in order to initiate treatment when sphincter disturbances become a problem. Surveillance: Evaluation every 6-12 months to update medications and physical rehabilitation.
SPAST-HSP is inherited in an autosomal dominant manner with age-related, nearly complete penetrance and is characterized by significant intrafamilial clinical variability. Most individuals diagnosed with SPAST-HSP have an affected parent. The proportion of cases caused by a de novo pathogenic variant is low. Each child of an individual with SPAST-HSP has a 50% chance of inheriting the pathogenic variant. Prenatal testing and preimplantation genetic diagnosis are possible if a pathogenic SPAST variant has been identified in an affected family member. Because of variable clinical expression, results of prenatal testing cannot be used to predict whether an individual will develop SPAST-HSP and, if so, what the age of onset, clinical course, and degree of disability will be.