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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. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	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.

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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.

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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).

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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.

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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.

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Unsteady gait

MedGen UID:: 68544
•Concept ID:: C0231686
•: Finding

A shaky or wobbly manner of walking.

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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.

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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.

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Abnormal cerebral white matter morphology

MedGen UID:: 181756
•Concept ID:: C0948163
•: Pathologic Function

An abnormality of the cerebral white matter.

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Hyperactive deep tendon reflexes

MedGen UID:: 335355
•Concept ID:: C1846176
•: Finding

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Distal sensory impairment

MedGen UID:: 335722
•Concept ID:: C1847584
•: Finding

An abnormal reduction in sensation in the distal portions of the extremities.

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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.

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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.

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Anemia

MedGen UID:: 1526
•Concept ID:: C0002871
•: Disease or Syndrome

A reduction in erythrocytes volume or hemoglobin concentration.

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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).

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Thrombocytopenia

MedGen UID:: 52737
•Concept ID:: C0040034
•: Disease or Syndrome

A reduction in the number of circulating thrombocytes.

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Hypoplastic anemia

MedGen UID:: 64229
•Concept ID:: C0178416
•: Disease or Syndrome

Anemia with varying degrees of erythrocytic hypoplasia without leukopenia or thrombocytopenia.

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Neutropenia

MedGen UID:: 163121
•Concept ID:: C0853697
•: Finding

An abnormally low number of neutrophils in the peripheral blood.

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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.

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Show all Hide all

Abnormality of blood and blood-forming tissues
Abnormality of limbs
- Ankle clonus
Abnormality of the eye
- Nystagmus
Abnormality of the immune system
- Neutropenia
Abnormality of the nervous system
Neoplasm
- Acute myelomonocytic leukemia M4

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVAtaxia-pancytopenia syndrome

Disorder of medulla oblongata
- Ataxia-pancytopenia syndrome

Follow this link to review classifications for Ataxia-pancytopenia syndrome in Orphanet.

Recent clinical studies

Diagnosis

Discovery of MIRAGE syndrome.

Narumi S
Pediatr Int 2022 Jan;64(1):e15283. doi: 10.1111/ped.15283. PMID: 35972063

Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy.

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

The Neuropathology of MIRAGE Syndrome.

Viaene AN, Harding BN
J Neuropathol Exp Neurol 2020 Apr 1;79(4):458-462. doi: 10.1093/jnen/nlaa009. PMID: 32106287

SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies.

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: 29535429 Free PMC Article

Ataxia-pancytopenia syndrome.

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

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Prognosis

Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L.

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: 27259050 Free PMC Article

See all (1)