Clinical Guidance

To date, 85 individuals from 36 families have been identified with a pathogenic variant in SAMD9L [; ; ; ; ; ; ; ; ; ; ; ; Author, unpublished data]. In addition, approximately 15% of children with myelodysplastic syndrome are found to have a germline pathogenic variant in SAMD9L. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Select Features of SAMD9L Ataxia-Pancytopenia Syndrome

Source: GeneReviews — "SAMD9L Ataxia-Pancytopenia Syndrome"

Penetrance

Given the variable expressivity of both hematologic and neurologic manifestations, the sometimes episodic asymptomatic cytopenias, the paucity of detailed neurologic/neuroimaging evaluations, and the effect of additional somatic genetic events on the hematologic manifestations , it is difficult to estimate the penetrance. However, the majority of persons with a pathogenic variant in SAMD9L will manifest some feature of the syndrome. There is no difference in range of manifestations for males and females. The phenomena of hematopoietic clones with additional genetic alterations repopulating the bone marrow appear to explain striking reports of non-penetrance or spontaneous and long-term disease remission in some affected individuals and some unaffected carrier parents of affected children .

Source: GeneReviews — "SAMD9L Ataxia-Pancytopenia Syndrome"

Differential Diagnosis

Hematologic disorders with neurologic manifestations. See .

Table 3.

Disorders to Consider in the Differential Diagnosis of SAMD9L Ataxia-Pancytopenia Syndrome

Gene(s) | Disorder | MOI | Hematologic Manifestations | Neurologic Manifestations | Other

ABCB7

| X-linked sideroblastic anemia ataxia(OMIM 301310) | XL | • Moderate hypochromic microcytic anemia w/o progression to marrow failure

• Not assoc w/malignancy

| Spinocerebellar syndrome in males1 |

ACD

CTC1

DKC1

NHP2

NOP10

PARN

RTEL1

TERC

TERT

TINF2

WRAP53

| Dyskeratosis congenita | XLADAR | • Progressive bone marrow failure

• Myelodysplasia

• Acute myeloid leukemia

| • Normal psychomotor development neurologic function in most persons

• See footnote 2 for exceptions.

| • Dysplastic nails

Source: GeneReviews — "SAMD9L Ataxia-Pancytopenia Syndrome"

Clinical Guidance

Nonsteroidal anti-inflammatory agents, anticoagulants, and thrombolytic agents are contraindicated if thrombocytopenia is present and should be used with caution given the fluctuating nature of the cytopenias. Avoid consuming alcohol and medications that cause sedation, which can increase problems with gait and coordination.

Source: GeneReviews — "SAMD9L Ataxia-Pancytopenia Syndrome"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SAMD9L Ataxia-Pancytopenia Syndrome"