Lymphoma, and Irritability

Medium match EHLERS-DANLOS SYNDROME, PERIODONTAL TYPE, 2; EDSPD2

• Autosomal dominant inheritance
• Scoliosis
• Neoplasm
• Fever
• Arthritis

SOURCES: OMIM MONDO UMLS

Medium match LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2

XLP2 is an X-linked primary immune deficiency with symptom onset usually in the first years of life, although later onset may occur. Features are compatible with immune dysregulation and include hemophagocytic lymphohistiocytosis (HLH), often associated with chronic Epstein-Barr virus (EBV) infection, splenomegaly, fever, colitis or inflammatory bowel disease (IBD), and recurrent infections. Laboratory abnormalities are variable, but can include hypogammaglobulinemia, cytopenias, and low levels of a particular subset of T cells known as NKT (or iNKT) cells. Functional studies show increased sensitivity of T cells to apoptosis (activation-induced cell death, AICD), impaired cytokine production, including of TNF-alpha (TNFA ), and general dysregulation of the immune pathway, such as increased levels of IL18 (OMIM ). However, circulating levels of lymphocytes and NK cells are usually normal. Many patients die from fulminant HLH, and the only curative treatment is a hematopoietic stem cell transplant, although this procedure has been associated with a poor prognosis. Female mutation carriers are usually asymptomatic, although some female carriers may have less severe manifestations, which appears to depend on X-inactivation patterns (summary by Yang et al., 2012; review by Latour and Aguilar, 2015).Latour and Aguilar (2015) provided a detailed review of XIAP deficiency, including clinical features, molecular genetics, and pathophysiology.For a general phenotypic description and a discussion of genetic heterogeneity of X-linked lymphoproliferative syndrome, see XLP1 (OMIM ).

LYMPHOPROLIFERATIVE SYNDROME, X-LINKED, 2; XLP2 Is also known as xiap deficiency

• Pica
• Ptosis
• Anemia
• Splenomegaly
• Fever

SOURCES: UMLS DOID OMIM GARD MESH MONDO NCIT

Medium match HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 1; FHL1

Zur Stadt et al. (2005) summarized the clinical features of hemophagocytic lymphohistiocytosis (HLH), a rare autosomal recessive disorder characterized by massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently central nervous system involvement. In FHL, the familial form of the disease, first episodes occur mostly during infancy, with a rapidly fatal outcome if untreated. Diagnostic criteria also include low fibrinogen and high triglyceride and ferritin levels. Chemoimmunotherapy based on corticosteroids, epipodophyllotoxins, and cyclosporin succeeds in controlling the disease in the majority of patients, although remission is rarely obtained (Henter et al., 2002). Most patients suffer an early death unless they are treated by hematopoietic stem cell transplantation (Durken et al., 1999). Genetic Heterogeneity of Familial Hemophagocytic LymphohistiocytosisFamilial hemophagocytic lymphohistiocytosis exhibits genetic heterogeneity. In some families, familial hemophagocytic lymphohistiocytosis has been found to be linked to chromosome 9q (HPLH1, FHL1). FHL2 (OMIM ) is caused by mutation in the PRF1 gene (OMIM ) on chromosome 10q22; FHL3 (OMIM ) is caused by mutation in the UNC13D gene (OMIM ) on chromosome 17q25; FHL4 (OMIM ) is caused by mutation in the syntaxin-11 gene (STX11 ) on chromosome 6q24; and FHL5 (OMIM ) is caused by mutation in the syntaxin-binding protein-2 (STXBP2 ), which is an interaction partner of STX11, on chromosome 19p13.Furthermore, before the identification of mutations in the RAG1 (OMIM ) and RAG2 (OMIM ) genes, both of which map to 11p, Omenn syndrome (familial reticuloendotheliosis with eosinophilia; {603554}) was not thought to be clearly distinct from other reported cases of hemophagocytic lymphohistiocytosis.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 1; FHL1 Is also known as hplh1, hlh1, hemophagocytic lymphohistiocytosis, familial;fhl;fhlh;hplh, reticulosis, familial histiocytic, hemophagocytic reticulosis, familial, erythrophagocytic lymphohistiocytosis, familial;fel

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: NCIT DOID MONDO ORPHANET ICD10 OMIM

Medium match CELIAC DISEASE, SUSCEPTIBILITY TO, 1; CELIAC1

Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy (GSE), is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). Long regarded as gastrointestinal disorder of childhood, the disease is now considered to be a chronic systemic autoimmune disease and is more often diagnosed in adults than in children (Monsuur et al., 2005).For a discussion of genetic heterogeneity of celiac disease, see MAPPING.

CELIAC DISEASE, SUSCEPTIBILITY TO, 1; CELIAC1 Is also known as celiac sprue, susceptibility to, 1, gluten-sensitive enteropathy, susceptibility to, 1

• Autosomal recessive inheritance
• Seizures
• Short stature
• Pica
• Ataxia

SOURCES: UMLS MONDO OMIM

Medium match POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY; PLOSL

Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities.

POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY; PLOSL Is also known as nasu-hakola disease;nhd, presenile dementia with bone cysts, dementia, prefrontal, with bone cysts, dementia, progressive, with lipomembranous polycystic osteodysplasia, brain-bone-fat disease;nhd; plo-sl; plosl; polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

• Autosomal recessive inheritance
• Seizures
• Pica
• Spasticity
• Pain

SOURCES: ORPHANET MESH UMLS DOID GARD MONDO SCTID OMIM

Low match CEROID LIPOFUSCINOSIS, NEURONAL, 4B, AUTOSOMAL DOMINANT; CLN4B

Neuronal ceroid lipofuscinosis-4B is an autosomal dominant neurodegenerative disorder characterized by onset of symptoms in adulthood. It belongs to a group of progressive neurodegenerative diseases characterized by accumulation of intracellular autofluorescent lipopigment storage material in the brain and other tissues. Several different forms have been described according to age of onset (see, e.g., CLN3, {204200}). Individuals with the adult form, sometimes referred to as Kufs disease, develop psychiatric manifestations, seizures, cerebellar ataxia, and cognitive decline. Retinal degeneration is usually not present (summary by Benitez et al., 2011 and Velinov et al., 2012).For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (OMIM ).

CEROID LIPOFUSCINOSIS, NEURONAL, 4B, AUTOSOMAL DOMINANT; CLN4B Is also known as kufs disease, autosomal dominant, ceroid lipofuscinosis, neuronal, parry type;

• Autosomal dominant inheritance
• Seizures
• Hearing impairment
• Ataxia
• Behavioral abnormality

SOURCES: OMIM MONDO DOID ORPHANET UMLS NCIT GARD

Low match ATYPICAL TERATOID RHABDOID TUMOR

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant central nervous system (CNS) rhabdoid tumor (RT; see this term) found almost exclusively in children.

ATYPICAL TERATOID RHABDOID TUMOR Is also known as atrt

• Seizures
• Ataxia
• Muscle weakness
• Macrocephaly
• Hydrocephalus

SOURCES: ORPHANET

Low match HUNTINGTON DISEASE-LIKE 2; HDL2

Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder considered part of the neuroacanthocytosis syndromes (see this term) characterized by a triad of movement, psychiatric, and cognitive abnormalities.

HUNTINGTON DISEASE-LIKE 2; HDL2 Is also known as ;hdl2

• Autosomal dominant inheritance
• Seizures
• Ataxia
• Hyperreflexia
• Dysarthria

SOURCES: MONDO DOID UMLS OMIM ORPHANET SCTID MESH

Low match ALZHEIMER DISEASE 4

Alzheimer's disease with an early onset (starts before the age of 65). It is caused by mutations in the PSEN2 gene.

ALZHEIMER DISEASE 4 Is also known as ad4, alzheimer disease, familial, 4

• Autosomal dominant inheritance
• Seizures
• Pica
• Tremor
• Depressivity

SOURCES: UMLS GARD NCIT MESH OMIM DOID MONDO

Low match LIVER FAILURE, INFANTILE, TRANSIENT; LFIT

Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009).See also transient infantile mitochondrial myopathy (MMIT ), which is a similar disorder.A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (OMIM ).See ILFS1 (OMIM ) for information on syndromic infantile liver failure.

LIVER FAILURE, INFANTILE, TRANSIENT; LFIT Is also known as ;acute infantile liver failure due to synthesis defect of mitochondrial dna-encoded proteins

• Autosomal recessive inheritance
• Generalized hypotonia
• Nevus
• Feeding difficulties
• Hepatomegaly

SOURCES: ORPHANET MONDO GARD OMIM UMLS