In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense. [orpha.net]

[…] half of the patients presenting missense mutations. [jnnp.bmj.com]

Dysphagia is present and Rombergism and pseudoathetosis are observed. NCVs and nerve biopsy reveal demyelinating and axonal features. Anti-GD1b or GQ1b (consistently present) antibodies, IgM paraproteins and cold agglutinins are present. [neuroweb.us]

Dysarthria and bladder dysfunction are often present. Cerebellar ataxia is common and some patients first present with this as a prominent sign in the first and second decades. [disorders.eyes.arizona.edu]

The full spectrum of diseases involving spasticity in adults and children and the unique diagnostic and management challenges they present is addressed by experienced clinicians. [books.google.com]

• Asymptomatic

  The father, brother, and uncle were both asymptomatic while the grandfather was wheelchairbound and the mother had abnormal gait. [omicsonline.org]

  Intra-familial phenotypic variations were observed, including age-at-onset, severity of spasticity, as well as the presence of asymptomatic carrier. [mdsabstracts.org]

  The phenotype was one of pure HSP with a wide range of disease severity with some patients requiring a wheelchair whereas others remained asymptomatic at the age of 40 years. [jnnp.bmj.com]

  The age of onset is variable and asymptomatic, yet affected, elderly relatives may be identified. In HSMN males are commonly affected, whereas females are more often asymptomatic. [neuroweb.us]

  The parents (II-1 and 2), who were first cousins, were neurologically asymptomatic. Arrow indicates the proband, and dots indicate the persons who permit analysis of their DNAs. [intechopen.com]

• Swelling

  Tendon Reflex (PTR) − ++ Achilles Tendon Reflex (ATR) + − − Babinski sign + + Vibration sense Normal Normal Sphincter involvement − − Mini-Mental State Examination (MMSE) 16/30 25/30 Lower limb NCV FWCV decreased Decreased Sural nerve biopsy Axonal swelling [intechopen.com]

• Diarrhea

  Moreover, a number of patients reported gastrointestinal problems, including constipation (14.6%), alternation of constipation and diarrhea (8.0%), fecal incontinence (11.6%), an inability to hold back stools (38.5%), and an at least daily occurrence [emedicine.medscape.com]

  Ethylene dioxide Herbicide : early manifestations are nausea, vomiting and diarrhea followed by a few days by painful paresthesias in the fingers and toes. Motor NCVs are slowed. [neuroweb.us]

  Complex hereditary spastic paraplegia Complex regional pain syndrome Complex regional pain syndrome type 1 Complex regional pain syndrome type 2 Cone rod dystrophy Congenital absence/hypoplasia of thumb Congenital adrenal hyperplasia Congenital chloride diarrhea [sanfordresearch.org]

• Muscle Weakness

  weakness Lower extremity weakness Lower limb weakness Muscle weakness in lower limbs [ more ] 0007340 Skeletal muscle atrophy Muscle degeneration Muscle wasting [ more ] 0003202 Spastic paraplegia 0001258 Variable expressivity 0003828 Showing of 24 | [rarediseases.info.nih.gov]

• Retinal Pigmentation

  pigmentation, mental retardation, deafness, optic atrophy or seizures [ 1, 2 ]. [bmcmedgenet.biomedcentral.com]

  Joshita Y, Yamamoto Y and Satoh Y (1982) Two siblings of familial spastic paraplegia with retinal pigment degeneration (sine pigment). Rinshō Shinkeigaku 22: 789–794. [els.net]

  However, occasional reports of abnormalities have included increased protein concentrations in complicated families and raised homocarnosine concentrations in a complicated family with spastic paraplegia, progressive mental deficiency, and retinal pigmentation [jnnp.bmj.com]

• Urinary Urgency

  Bowel urgency is less common but may occur. Medications such as oxybutynin may reduce urinary urgency. If urinary urgency is severe or accompanied by difficulty initiating urination, consultation with a urologist is recommended. [rarediseases.org]

  urgency Overactive bladder 0000012 Percent of people who have these symptoms is not available through HPO Ankle clonus Abnormal rhythmic movements of ankle 0011448 Autosomal dominant inheritance 0000006 Babinski sign 0003487 Lower limb muscle weakness [rarediseases.info.nih.gov]

• Urinary Retention

  Autonomic dysfunction in form of tachycardia, hypertension, and urinary retention are common. NCVs are consistent with axonal neuropathy. Very often patients are labeled as hysterical and have a drug-seeking behavior. [neuroweb.us]

  Hokkaido J Med Sci 80 185-189 2005年 [査読有り] A case of acute urinary retention caused by periaqueductal grey (PAG) lesion. Yaguchi, H., Soma, H., Miyazaki, Y., Tashiro, J., Yabe, I. [researchmap.jp]

• Hyperreflexia

  Paraplegia 24, Autosomal Recessive Summaries for Spastic Paraplegia 24, Autosomal Recessive Symptoms & Phenotypes for Spastic Paraplegia 24, Autosomal Recessive Symptoms via clinical synopsis from OMIM: 57 Neurologic Central Nervous System: spasticity hyperreflexia [malacards.org]

  Neurologic examination revealed hyperreflexia and spasticity in the lower extremities, weakness of hip flexion and ankle dorsiflexion, extensor plantar response, diminished vibratory sense in the feet, and pes cavus. [neurology.org]

  […] in upper limbs 0007350 Impaired proprioception 0010831 Lower limb hyperreflexia Overactive lower leg reflex 0002395 Pes cavus High-arched foot 0001761 Proximal lower limb amyotrophy Wasting of thigh muscle 0008956 5%-29% of people have these symptoms [rarediseases.info.nih.gov]

• Spastic Gait

  […] with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood or adulthood (>30 years). [orpha.net]

  Orpha Number: 101011 Disease definition A rare type of hereditary spastic paraplegia usually characterized by a pure phenotype of proximal weakness of the lower extremities with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood [rarediseases.info.nih.gov]

• Seizure

  In addition, the sister carrying the R294H variant had several prolonged febrile seizures; her sister only had a single febrile seizure. Spasticity was not noted at age 20 in the sister carrying the pathogenic variant. From EE to HSP. [epilepsygenetics.net]

  In patients with a pure HSP kindred, the presence of additional deficits, such as visual disturbance, marked muscle wasting, fasciculations, dementia, seizures, and peripheral neuropathy, should not be attributed to variant presentations of pure HSP. [emedicine.medscape.com]

  In our cohort, we report 4.7% of patients with genetically diagnosed spastin mutation and learning disabilities and 3.5% of seizures. Interestingly, all three cases with seizures reported in our study were associated with cognitive deficit. [jnnp.bmj.com]

  Axenfeld-Rieger syndrome B-cell chronic lymphocytic leukemia Babesiosis Bannayan-Riley-Ruvalcaba syndrome Baroreflex Failure Barrett esophagus Bazex-Dupre-Christol syndrome Beckwith-Wiedemann syndrome Behcet disease Benign essential blepharospasm Benign focal seizures [sanfordresearch.org]

• Tremor

  Gilbert directs the Movement Disorders and Tourette's Syndrome Clinics, which specialize in evaluation and pharmacologic treatment of tics, chorea, tremor, dystonia, stereotypies, ataxia, and other movement disorders http://www.cincinnatichildrens.org [books.google.com]

  Jerky tremor was also noticed bilaterally in the hands while reaching to grab objects. Over time, he also developed bilateral upper-extremity rest tremor. His gait became stiff and he developed postural instability and near falling. [movementdisorders.org]

  Parkinsonism, with symptoms such as tremor, abnormal slowness of movement and an inability to remain in a stable or balanced position, may also occur. Onset can range from infancy to mid-adulthood. [flybase.org]

  The sister carrying the R294H variant had an ataxic gait and hand tremor at 3 years, which was not present in her sister. [epilepsygenetics.net]

  E - beta-thalassemia Hereditary cerebral cavernous malformation Hereditary chronic pancreatitis Hereditary coproporphyria Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia Hereditary episodic ataxia Hereditary essential tremor [sanfordresearch.org]

• Babinski Sign

  Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. [rarediseases.info.nih.gov]

High-arched feet (pescavus) are generally present and are usually prominent in older patients. workup Genetic Testing 43. Imaging Studies MRI scans may demonstrate atrophy of the spinal cord. [slideshare.net]

Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. [link.springer.com]

A Doody's Core Title 2012 Spasticity: Diagnosis and Management is the first book solely dedicated to the diagnosis and treatment of spasticity. [books.google.com]

Treatment Treatment Options: No treatment is known for the basic disease but physical therapy and low vision aids are likely beneficial. [disorders.eyes.arizona.edu]

The information obtained from validated rating scales (SPRS and SF-36), TMS, and serum biomarkers, will allow for the development of treatment trials. [clinicaltrials.gov]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

This network is dedicated to the acceleration of clinical trials in search of effective treatments for SMA. [books.google.ro]

Prognosis: predicting symptoms and course of HSP As noted above, there is significant variation in HSP symptoms and their severity. This limits the certainty of making predictions. [rarediseases.org]

Prognosis [ edit ] Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. [en.wikipedia.org]

Favorable prognosis is indicated by preserved action potential preserved R1 or reappearance of R1 after 3 weeks. About 15% of patients will have permanent sequelae. [neuroweb.us]

Disorders, the prognosis of which differs significantly from HSP, such as multiple sclerosis and familial motor neuron disease should also be excluded. The necessity for investigations will vary depending on the individual clinical picture. [jnnp.bmj.com]

The wide range of disease severity and the overlapping of many signs can make pedigree construction and the determination of recurrence risks and prognosis challenging. The only recourse may be genotyping. [disorders.eyes.arizona.edu]

The increasing availability of WES in clinical practice will undoubtedly broaden the known clinical and etiological spectrum of DRD. Our case supports the notion that DRD is a syndrome with multiple etiologies and clinical phenomenologies. [movementdisorders.org]

Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet 1987 ; 41 : 933 –43 ↵ Goldblatt J, Ballo R, Sachs B, et al. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype. [ajnr.org]

Arthrogryposis (multiple congenital contractures): Diagnostic approach to etiology, classification, genetics, and general principles. European Journal of Medical Genetics, 57(8), 464-472. doi:10.1016/j.ejmg.2014.03.008 Request Information [igenomix.es]

Early ( 45 years) and late-onset RLS differ etiologically. [neuroweb.us]

Consequently, they are often approached together in epidemiological studies. [karger.com]

A population-based survey from 1993-2004 and a retrospective medical record review allowed a systematic review of clinical, genetic, and epidemiologic features of 89 Portuguese families, who had a total of 239 patients with autosomal dominant hereditary [medscape.com]

Relevant External Links for REEP1 Genetic Association Database (GAD) REEP1 Human Genome Epidemiology (HuGE) Navigator REEP1 Atlas of Genetics and Cytogenetics in Oncology and Haematology: REEP1 No data available for Genatlas for REEP1 Gene Autosomal dominant [genecards.org]

The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014; 42(3):174-83. [invitae.com]

Spasticity: Diagnosis and Management clearly defines the process for the diagnosis of spasticity, the basic science behind its pathophysiology, the measurement tools used for evaluation, and reviews the available treatment options. [books.google.com]

DESIGN This is an observational study of autosomal dominant forms of hereditary spastic paraplegia progression, pathophysiology, and biomarkers. [clinicaltrials.gov]

PATHOPHYSIOLOGY 6. Impaired cellular membrane trafficking 7. More particularly axonal transport of macromolecules and organelles. 8. Mutation of proteins, spastin and atlastin-1 causes impaired cellular membrane trafficking. [slideshare.net]

Pathophysiology [ edit ] The major feature of HSP is a length dependent axonal degeneration. [21] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. [en.wikipedia.org]

Treating hereditary spastic paraplegia It isn't possible to prevent, slow or reverse hereditary spastic paraplegia, but some of the symptoms can be managed so that day-to-day activities become easier. [nhs.uk]

TREATMENT Currently, no specific treatment exists to prevent, retard, or reverse progressive disability in patients with HSP. [slideshare.net]

Treatment [ edit ] No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. [en.wikipedia.org]

Extra genetic material from the X chromosome interferes with male sexual development, preventing the testicles from functioning normally, males with Klinefelter syndrome typically have one extra copy of the X chromosome in each cell, for a total of two [wikivisually.com]

Advances in genetic research in the last decades have improved their diagnosis and brought new possibilities for prevention and future treatments. Still, there is great uncertainty regarding their global epidemiology. [karger.com]