Patient Information

HEREDITARY SPASTIC PARAPLEGIA (HSP)

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MGZMedical Genetics Center

3 PROGRESSION AND TREATMENT

HSPs are chronic, progressive diseases, although severityand the progression of the disease may vary greatlydepending on the genetically defined form. Patients withuncomplicated HSP usually retain full strength and mobilityof the upper extremities and have no difficulties speaking,chewing or swallowing. Although symptoms can be restrict-ing, lifespan is not shortened by HSP.

Although, with exceptions, current treatment optionsdon't target genetic causes, quality of life, course of thedisease and prognosis can be improved by early detectionof symptoms and specific associated disease risks. Thesecan be addressed by physiotherapy, orthopedic measures,or symptomatic pharmacological treatment.

3 SELF-HELP GROUPS/USEFUL ADDRESSES

1 Orphanet. The platform for rare diseases and orphan drugs. www.orpha.net

On our website you will find additional information onother clinical topics as well as organizational information.Visit us at www.mgz-muenchen.com

MGZ – Medical Genetics CenterProf. Elke Holinski-Feder, MD

Angela Abicht, MDClinical Geneticists, MVZ

Bayerstrasse 3 - 5 | D-80335 MunichPhone +49 (0)89 / 30 90 886 - 0 | Fax +49 (0)89 / 30 90 886 - 66

inquiry@mgz-muenchen.com | www.mgz-muenchen.com Vers

ion

2018

-06

Prof. Elke Holinski-Feder, MD

Angela Abicht, MD

Clinical Geneticists

Stefanie Balg, MDBrigitte SchönfeldTeresa Neuhann, MDKerstin Becker, MDDaniela González FassrainerVerena Steinke-Lange, MDYvonne Müller-Koch, MDAnne Behnecke, MDClinical Geneticists

Silja Gnann, MDInternistClinical Geneticist

Isabel Diebold, MDPediatrician

MGZ – Medical Genetics CenterBayerstrasse 3 - 5 (Entrance: Schlosserstrasse 6)80335 Munich

Munich Central Station

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Disease onset can occur from early childhood to lateradulthood. A peak of disease onset is observed in infancyand around age 40, although this is also determined bythe respective genetically determined sub-form of the disease.

The overall frequency (prevalence) of HSPs is estimatedto be 1:10,000 (1 in 10,000 people affected by disease inthe general population). It is therefore relatively commonamong the ”rare diseases“.

3 GENETIC CAUSES

The HSPs are diseases that are caused by a change in thegenetic material.

The genetic material is present in every human being in theform of DNA molecules that, in certain sequences, form theso-called genes. The genes are the blueprint that underliesall processes in the human body. Pathological gene changesare called mutations or pathogenic variants.

In case of HSPs, there are a variety of different geneswhose alterations lead to genetically defined forms ofHSP. These various sub-forms have heterogeneous bio-logical causes and therefore differ with regard to fre-quency of occurrence, inheritance, disease-associatedsymptoms, and sometimes therapeutic approach.

3 INHERITANCE

The DNA, which is the genetic material of humans, formstwo sets of 23 chromosomes each. One set of chromosomesis inherited from the mother, the other one from the father.

Dear patient,

This booklet summarizes information about the basics ofthe disease, the hereditary aspects, as well as medicalcare.

3 HEREDITARY SPASTIC PARAPLEGIA

The group of hereditary spastic paraplegias (HSPs)includes various neurological diseases of genetic originwith the leading symptom of progressive spastic paralysisof the legs (= spastic paraplegias).

Spasticity refers to an increased intrinsic tension of the mus-cles, which usually presents itself with a decrease in musclestrength (= paresis) and increased reflexes. It is caused bydamage to the motor pathways of the central nervous sys-tem (brain or spinal cord).

For the patient, the disease is initially perceived as anunsteady gait or weakness of the legs while walking.

1 HSPs are referred to as ”pure“ or ”uncompli-cated“, if symptoms are mainly limited to spasticparaplegia of the legs. However, this is oftenaccompanied by a bladder disorder that can man-ifest as urge incontinence or difficulty emptying thebladder.

1 By contrast, in ”complex“ or ”complicated“ forms,a wide variety of additional neurological symptomscan arise. These notably include disorders of thecerebellar function, which manifest as dizziness orunsteady gait (ataxia) or difficulty speaking(dysarthria).

The inheritance of HSPs depends on the geneticallydefined subtype of the individual patient. As many differ-ent subtypes exist, all modes of inheritance (autosomaldominant, autosomal recessive, X-linked or mitochondrial)are possible. The risk of disease occurrence in genetic rel-atives or offspring depends on the underlying inheritanceand can differ greatly.

Genetically-induced HSP cannot be ruled out if there areno other affected family members.

If the family includes affected persons in several genera-tions, this can indicate autosomal dominant inheritance.In this case, in about half of the cases, the most commonform of HSP is present (SPG4), which results from geneticmodification of the SPAST gene.

In the context of human genetic counseling - should thecausative genetic change be identified – the mode offamilial inheritance, as well as individual risk of havingaffected offspring can be determined, and possibilities forfamily planning can be discussed.

3 DIAGNOSIS

Even if a characteristic clinical presentation suggests anHSP, the diagnosis and delimitation of non-genetic differ-ential diagnoses is made by a human genetic analysis froma blood sample. Only by detecting the underlying geneticchange, can the disease be categorized as one of thenumerous genetically determined forms of HSP.

However, as there are still scientifically unexplainedgenetic causes, it is not always possible to confirm thediagnosis genetically. Depending on the family history andthe scope of the examination, this is possible in 30 - 70%of patients.