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Ataxia-pancytopenia syndrome(ATXPC)

MedGen UID:
230896
Concept ID:
C1327919
Disease or Syndrome
Synonyms: ATXPC; Myelocerebellar disorder
SNOMED CT: Ataxia pancytopenia syndrome (768556005); Myelocerebellar disorder (768556005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): SAMD9L (7q21.2)
 
Monarch Initiative: MONDO:0008038
OMIM®: 159550
Orphanet: ORPHA2585

Disease characteristics

Excerpted from the GeneReview: SAMD9L Ataxia-Pancytopenia Syndrome
SAMD9L ataxia-pancytopenia (ATXPC) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure, myelodysplasia, and myeloid leukemia, sometimes associated with monosomy 7. The onset of hematologic abnormalities has been reported as early as age three months. The cytopenias in all cell lineages range from mild to very severe. Onset of neurologic impairment is variable. Nystagmus, dysmetria, increased deep tendon reflexes, and clonus are common. Gait impairment and other neurologic abnormalities are slowly progressive. [from GeneReviews]
Authors:
Wendy H Raskind  |  Dong-Hui Chen  |  Thomas Bird   view full author information

Additional descriptions

From OMIM
Ataxia-pancytopenia syndrome (ATXPC) is an autosomal dominant disorder characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to bone marrow failure and myeloid leukemia. The germline genetic defect is associated with somatic loss of chromosome 7 (monosomy 7) resulting in the deletion of several genes on chromosome 7 that may predispose to the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) (summary by Chen et al., 2016 and Tesi et al., 2017).  http://www.omim.org/entry/159550
From MedlinePlus Genetics
Ataxia-pancytopenia syndrome is a rare condition that affects the part of the brain that coordinates movement (the cerebellum) and blood-forming cells in the bone marrow. The age when signs and symptoms begin, the severity of the condition, and the rate at which it worsens all vary among affected individuals.

People with ataxia-pancytopenia syndrome have neurological problems associated with a loss of tissue (atrophy) and other changes in the cerebellum. These problems include poor coordination and balance (ataxia), difficulty with movements that involve judging distance or scale (dysmetria), uncontrollable muscle contractions (clonus), and involuntary back-and-forth eye movements (nystagmus). These neurological issues worsen over time, making walking and other movements challenging. Some affected individuals eventually require wheelchair assistance.

Ataxia-pancytopenia syndrome also causes a shortage of one or more types of normal blood cells: red blood cells, white blood cells, and platelets. A shortage of all three of these cell types is known as pancytopenia. Pancytopenia can result in extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and abnormal bleeding due to low numbers of platelets (thrombocytopenia). Ataxia-pancytopenia syndrome is also associated with an increased risk of certain cancerous conditions of the blood, particularly myelodysplastic syndrome and acute myeloid leukemia.  https://medlineplus.gov/genetics/condition/ataxia-pancytopenia-syndrome

Clinical features

From HPO
Acute myelomonocytic leukemia M4
MedGen UID:
9732
Concept ID:
C0023479
Neoplastic Process
An acute leukemia characterized by the proliferation of both neutrophil and monocyte precursors.
Ankle clonus
MedGen UID:
68672
Concept ID:
C0238651
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Hyperactive deep tendon reflexes
MedGen UID:
335355
Concept ID:
C1846176
Finding
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Impaired vibration sensation in the lower limbs
MedGen UID:
338617
Concept ID:
C1849134
Finding
A decrease in the ability to perceive vibration in the legs.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Hypoplastic anemia
MedGen UID:
64229
Concept ID:
C0178416
Disease or Syndrome
Anemia with varying degrees of erythrocytic hypoplasia without leukopenia or thrombocytopenia.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAtaxia-pancytopenia syndrome
Follow this link to review classifications for Ataxia-pancytopenia syndrome in Orphanet.

Recent clinical studies

Diagnosis

Narumi S
Pediatr Int 2022 Jan;64(1):e15283. doi: 10.1111/ped.15283. PMID: 35972063
Vaughan D, Bogdanova-Mihaylova P, Costello DJ, Sweeney BJ, McNamara B, Walsh RA, Murphy SM
J Peripher Nerv Syst 2020 Dec;25(4):433-437. Epub 2020 Sep 9 doi: 10.1111/jns.12409. PMID: 32808377
Viaene AN, Harding BN
J Neuropathol Exp Neurol 2020 Apr 1;79(4):458-462. doi: 10.1093/jnen/nlaa009. PMID: 32106287
Davidsson J, Puschmann A, Tedgård U, Bryder D, Nilsson L, Cammenga J
Leukemia 2018 May;32(5):1106-1115. Epub 2018 Feb 25 doi: 10.1038/s41375-018-0074-4. PMID: 29535429Free PMC Article
González-del Angel A, Cervera M, Gómez L, Pérez-Vera P, Orozco L, Carnevale A, Del Castillo V
Am J Med Genet 2000 Jan 31;90(3):252-4. doi: 10.1002/(sici)1096-8628(20000131)90:3<252::aid-ajmg14>3.3.co;2-m. PMID: 10678666

Prognosis

Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH
Am J Hum Genet 2016 Jun 2;98(6):1146-1158. doi: 10.1016/j.ajhg.2016.04.009. PMID: 27259050Free PMC Article

Clinical prediction guides

Viaene AN, Harding BN
J Neuropathol Exp Neurol 2020 Apr 1;79(4):458-462. doi: 10.1093/jnen/nlaa009. PMID: 32106287
Thunström S, Axelsson M
BMC Neurol 2019 May 3;19(1):89. doi: 10.1186/s12883-019-1319-1. PMID: 31053103Free PMC Article
Chen DH, Below JE, Shimamura A, Keel SB, Matsushita M, Wolff J, Sul Y, Bonkowski E, Castella M, Taniguchi T, Nickerson D, Papayannopoulou T, Bird TD, Raskind WH
Am J Hum Genet 2016 Jun 2;98(6):1146-1158. doi: 10.1016/j.ajhg.2016.04.009. PMID: 27259050Free PMC Article

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