Anemia, and Osteopenia

Medium match OSTEOPETROSIS, AUTOSOMAL DOMINANT 3; OPTA3

Autosomal dominant osteopetrosis-3 is characterized by phenotypic variability. Some patients have typical features of osteopetrosis, including fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density, whereas other patients exhibit localized osteosclerosis and generalized osteopenia. OPTA3 represents a relatively malignant form of osteopetrosis in some patients who develop significant pancytopenia and hepatosplenomegaly (Bo et al., 2016).For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (OMIM ).

• Anemia
• Fatigue
• Headache
• Osteoporosis
• Osteopenia

SOURCES: OMIM MENDELIAN

Medium match LEUKOENCEPHALOPATHY, BRAIN CALCIFICATIONS, AND CYSTS; LCC

Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome, is characterized by a constellation of features restricted to the central nervous system, including leukoencephalopathy, brain calcifications, and cysts, resulting in spasticity, dystonia, seizures, and cognitive decline (summary by Labrune et al., 1996).See also cerebroretinal microangiopathy with calcifications and cysts (CRMCC ), an autosomal recessive disorder caused by mutation in the CTC1 gene (OMIM ) that shows phenotypic similarities to Labrune syndrome. CRMCC includes the neurologic findings of intracranial calcifications, leukodystrophy, and brain cysts, but also includes retinal vascular abnormalities and other systemic manifestations, such as osteopenia with poor bone healing, a high risk of gastrointestinal bleeding, hair, skin, and nail changes, and anemia and thrombocytopenia. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012).

LEUKOENCEPHALOPATHY, BRAIN CALCIFICATIONS, AND CYSTS; LCC Is also known as labrune syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Spasticity

SOURCES: OMIM MESH MENDELIAN

Medium match PANCREATIC INSUFFICIENCY-ANEMIA-HYPEROSTOSIS SYNDROME

This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis.

• Global developmental delay
• Failure to thrive
• Anemia
• Hepatomegaly
• Splenomegaly

SOURCES: ORPHANET MESH OMIM MENDELIAN

Medium match ATYPICAL GAUCHER DISEASE DUE TO SAPOSIN C DEFICIENCY

• Seizures
• Ataxia
• Anemia
• Dysarthria
• Tremor

SOURCES: OMIM MESH ORPHANET MENDELIAN

Medium match SHORT STATURE WITH MICROCEPHALY AND DISTINCTIVE FACIES

• Global developmental delay
• Microcephaly
• Growth delay
• Abnormal facial shape
• Anemia

SOURCES: OMIM MENDELIAN

Medium match CONGENITAL ERYTHROPOIETIC PORPHYRIA

Congenital erythropoietic porphyria, or Günther disease, is a form of erythropoietic porphyria characterized by very severe and mutilating photodermatosis.

CONGENITAL ERYTHROPOIETIC PORPHYRIA Is also known as cep|gÜnther disease

• Splenomegaly
• Immunodeficiency
• Thrombocytopenia
• Osteopenia
• Abnormality of the foot

SOURCES: ORPHANET MENDELIAN

Medium match BETA-THALASSEMIA

Beta-thalassemia is characterized by a reduced production of hemoglobin A (HbA, alpha-2/beta-2), which results from the reduced synthesis of beta-globin chains relative to alpha-globin chains, thus causing an imbalance in globin chain production and hence abnormal erythropoiesis. The disorder is clinically heterogeneous (summary by Ottolenghi et al., 1975).Absence of beta globin causes beta-zero-thalassemia. Reduced amounts of detectable beta globin causes beta-plus-thalassemia. For clinical purposes, beta-thalassemia is divided into thalassemia major (transfusion dependent), thalassemia intermedia (of intermediate severity), and thalassemia minor (asymptomatic, carrier state). The molecular and clinical aspects of the beta-thalassemias were reviewed by Olivieri (1999).The remarkable phenotypic diversity of the beta-thalassemias reflects the heterogeneity of mutations at the HBB locus, the action of many secondary and tertiary modifiers, and a wide range of environmental factors (Weatherall, 2001).

• Growth delay
• Failure to thrive
• Muscle weakness
• Anemia
• Feeding difficulties

SOURCES: OMIM ORPHANET MENDELIAN

Medium match MULTIPLE MYELOMA

Multiple myeloma (MM) is a malignant tumor of plasma cell characterized by overproduction of abnormal plasma cells in the bone marrow and skeletal destruction. The clinical features are bone pain, renal impairment, immunodeficiency, anemia and presence of abnormal immunoglobulins (Ig).

MULTIPLE MYELOMA Is also known as plasma cell myeloma|myelomatosis|kahler's disease|medullary plasmacytoma

• Neoplasm
• Anemia
• Fatigue
• Splenomegaly
• Weight loss

SOURCES: ORPHANET OMIM MENDELIAN

Medium match PORPHYRIA, CONGENITAL ERYTHROPOIETIC

The porphyrias are diseases caused by defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver (Gross et al., 2000).Desnick and Astrin (2002) provided a comprehensive review of congenital erythropoietic porphyria pathogenesis and treatment.One patient with a phenotype suggestive of congenital erythropoietic anemia was found to have a mutation in the GATA1 gene ({305371.0010}) that affected UROS expression (see XLTT, {314050}).

PORPHYRIA, CONGENITAL ERYTHROPOIETIC Is also known as cep|uros deficiency|uroporphyrinogen iii synthase deficiency|gunther disease

• Short stature
• Anemia
• Splenomegaly
• Thrombocytopenia
• Alopecia

SOURCES: OMIM ORPHANET MENDELIAN

Medium match ROTHMUND-THOMSON SYNDROME TYPE 2

Rothmund-Thomson syndrome type 2 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, congenital bone defects and an increased risk of osteosarcoma in childhood and squamous cell carcinoma later in life.

ROTHMUND-THOMSON SYNDROME TYPE 2 Is also known as poikiloderma of rothmund-thomson type 2|rts2

• Growth delay
• Cataract
• Anemia
• Frontal bossing
• Diarrhea

SOURCES: ORPHANET MENDELIAN