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Classic dopamine transporter deficiency syndrome(PKDYS1)

MedGen UID:
1814585
Concept ID:
C5700336
Disease or Syndrome
Synonyms: DOPAMINE TRANSPORTER DEFICIENCY SYNDROME; Parkinsonism-dystonia, infantile, 1; PKDYS1
 
SLC6A3 (5p15.33)
 
Monarch Initiative: MONDO:0054835
OMIM®: 613135

Disease characteristics

SLC6A3-related dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder with a continuum that ranges from classic early-onset DTDS (by age 6 months) to atypical later-onset DTDS (in childhood, adolescence, or adulthood). Classic early-onset DTDS: Infants typically manifest nonspecific findings (irritability, feeding difficulties, axial hypotonia, and/or delayed motor development) followed by a hyperkinetic movement disorder (with features of chorea, dystonia, ballismus, orolingual dyskinesia). Over time, affected individuals develop parkinsonism-dystonia characterized by bradykinesia (progressing to akinesia), dystonic posturing, distal tremor, rigidity, and reduced facial expression. Limitation of voluntary movements leads to severe motor delay. Episodic status dystonicus, exacerbations of dystonia, and secondary orthopedic, gastrointestinal, and respiratory complications are common. Many affected individuals appear to show relative preservation of intellect with good cognitive development. Atypical later-onset DTDS: Normal psychomotor development in infancy and early childhood. Attention-deficit/hyperactivity disorder (ADHD) is reported in childhood followed by later-onset manifestations of parkinsonism-dystonia with tremor, progressive bradykinesia, variable tone, and dystonic posturing. The long-term prognosis of this form of DTDS is currently unknown. [from GeneReviews]
Authors:
Robert VV Spaull  |  Manju A Kurian   view full author information

Additional descriptions

From OMIM
Infantile-onset parkinsonism-dystonia-1 (PKDYS1), also known as dopamine transporter deficiency syndrome (DTDS), is an autosomal recessive complex motor neurologic disorder with onset in infancy. Affected individuals show hyperkinesia with orolingual and limb dyskinesia, dystonia, and chorea, or hypokinesia with parkinsonian features, such as bradykinesia, rigidity, and tremor. Other features may include axial hypotonia, pyramidal tract signs, and eye movement abnormalities. Many patients are misdiagnosed as having cerebral palsy. Cognitive function appears to be less severely affected, but most patients die in the teenage years. There is no effective treatment. Laboratory studies show an increased ratio of homovanillic acid (HVA) to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), which represents an increased ratio of dopamine to serotonin metabolites (review by Kurian et al., 2011). Genetic Heterogeneity of Infantile- or Childhood-Onset Parkinsonism-Dystonia See also PKDYS2 (618049), caused by mutation in the SLC18A2 gene (193001) on chromosome 10q25, and PKDYS3 (619738), caused by mutation in the WARS2 gene (604473) on chromosome 1p12. For an overlapping phenotype, see tyrosine hydroxylase deficiency (605407), also known as autosomal recessive Segawa syndrome.  http://www.omim.org/entry/613135
From MedlinePlus Genetics
Dopamine transporter deficiency syndrome is a rare movement disorder. The condition is also known as infantile parkinsonism-dystonia because the problems with movement (dystonia and parkinsonism, described below) usually start in infancy and worsen over time. However, the features of the condition sometimes do not appear until childhood or later.

People with dopamine transporter deficiency syndrome develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia is widespread (generalized), affecting many different muscles. The continuous muscle cramping and spasms cause difficulty with basic activities, including speaking, eating, drinking, picking up objects, and walking.

As the condition worsens, affected individuals develop parkinsonism, which is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, and an inability to hold the body upright and balanced (postural instability). Other signs and symptoms that can develop include abnormal eye movements; reduced facial expression (hypomimia); disturbed sleep; frequent episodes of pneumonia; and problems with the digestive system, including a backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.

People with dopamine transporter deficiency syndrome may have a shortened lifespan, although the long-term effects of this condition are not fully understood. Children with this condition have died from pneumonia and breathing problems. When the first signs and symptoms appear later in life, affected individuals may survive into adulthood.  https://medlineplus.gov/genetics/condition/dopamine-transporter-deficiency-syndrome

Clinical features

From HPO

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Balint B, Bhatia KP
Eur J Neurol 2015 Apr;22(4):610-7. Epub 2015 Jan 29 doi: 10.1111/ene.12650. PMID: 25643588
Wong DF, Harris JC, Naidu S, Yokoi F, Marenco S, Dannals RF, Ravert HT, Yaster M, Evans A, Rousset O, Bryan RN, Gjedde A, Kuhar MJ, Breese GR
Proc Natl Acad Sci U S A 1996 May 28;93(11):5539-43. doi: 10.1073/pnas.93.11.5539. PMID: 8643611Free PMC Article

Diagnosis

Balint B, Bhatia KP
Eur J Neurol 2015 Apr;22(4):610-7. Epub 2015 Jan 29 doi: 10.1111/ene.12650. PMID: 25643588
Cummings JL, Fine MJ, Grachev ID, Jarecke CR, Johnson MK, Kuo PH, Schaecher KL, Oberdorf JA, Rezak M, Riley DE, Truong D
Am J Manag Care 2014 Mar;20(5 Suppl):S97-109. PMID: 24773455
Ng J, Zhen J, Meyer E, Erreger K, Li Y, Kakar N, Ahmad J, Thiele H, Kubisch C, Rider NL, Morton DH, Strauss KA, Puffenberger EG, D'Agnano D, Anikster Y, Carducci C, Hyland K, Rotstein M, Leuzzi V, Borck G, Reith ME, Kurian MA
Brain 2014 Apr;137(Pt 4):1107-19. Epub 2014 Mar 10 doi: 10.1093/brain/awu022. PMID: 24613933Free PMC Article

Therapy

Cummings JL, Fine MJ, Grachev ID, Jarecke CR, Johnson MK, Kuo PH, Schaecher KL, Oberdorf JA, Rezak M, Riley DE, Truong D
Am J Manag Care 2014 Mar;20(5 Suppl):S97-109. PMID: 24773455

Prognosis

Ng J, Zhen J, Meyer E, Erreger K, Li Y, Kakar N, Ahmad J, Thiele H, Kubisch C, Rider NL, Morton DH, Strauss KA, Puffenberger EG, D'Agnano D, Anikster Y, Carducci C, Hyland K, Rotstein M, Leuzzi V, Borck G, Reith ME, Kurian MA
Brain 2014 Apr;137(Pt 4):1107-19. Epub 2014 Mar 10 doi: 10.1093/brain/awu022. PMID: 24613933Free PMC Article

Clinical prediction guides

Wong DF, Harris JC, Naidu S, Yokoi F, Marenco S, Dannals RF, Ravert HT, Yaster M, Evans A, Rousset O, Bryan RN, Gjedde A, Kuhar MJ, Breese GR
Proc Natl Acad Sci U S A 1996 May 28;93(11):5539-43. doi: 10.1073/pnas.93.11.5539. PMID: 8643611Free PMC Article

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