Delayed speech and language development, and Lymphadenopathy

Medium match AICARDI-GOUTIERES SYNDROME 7; AGS7

Aicardi-Goutieres syndrome-7 is an autosomal dominant inflammatory disorder characterized by severe neurologic impairment. Most patients present in infancy with delayed psychomotor development, axial hypotonia, spasticity, and brain imaging changes, including basal ganglia calcification, cerebral atrophy, and deep white matter abnormalities. Laboratory evaluation shows increased alpha-interferon (IFNA1 ) activity with upregulation of interferon signaling and interferon-stimulated gene expression. Some patients may have normal early development followed by episodic neurologic regression (summary by Rice et al., 2014).For a phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (OMIM ).

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: UMLS MONDO OMIM

Low match IMMUNODEFICIENCY 8; IMD8

IMMUNODEFICIENCY 8; IMD8 Is also known as ;scid due to coro1a deficiency; scid due to coronin-1a deficiency; severe combined immunodeficiency due to coronin-1a deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Cognitive impairment
• Anemia

SOURCES: ORPHANET DOID MONDO OMIM UMLS

Low match AUTOIMMUNE HEMOLYTIC ANEMIA-AUTOIMMUNE THROMBOCYTOPENIA-PRIMARY IMMUNODEFICIENCY SYNDROME

AUTOIMMUNE HEMOLYTIC ANEMIA-AUTOIMMUNE THROMBOCYTOPENIA-PRIMARY IMMUNODEFICIENCY SYNDROME Is also known as evans syndrome associated with primary immunodeficiency; tppii deficiency; tppii-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion disease; triangle disease; tripeptidyl-peptidase ii deficiency

• Splenomegaly
• Respiratory tract infection
• Autoimmunity
• Lymphadenopathy
• Stroke

SOURCES: ORPHANET

Low match IMMUNODEFICIENCY 36; IMD36

IMD36 is a primary immunodeficiency with a highly heterogeneous clinical phenotype, characterized primarily by recurrent respiratory tract infections, lymphoproliferation, and antibody deficiency. Other features include growth retardation, mild neurodevelopmental delay, and autoimmunity. The major complication is development of B-cell lymphoma (Elkaim et al., 2016).

• Autosomal dominant inheritance
• Global developmental delay
• Growth delay
• Splenomegaly
• Diarrhea

SOURCES: MONDO UMLS OMIM

Low match PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY

Purine nucleoside phosphorylase (PNP) deficiency is a disorder of purine metabolism characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.

PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY Is also known as nucleoside phosphorylase deficiency;pnp deficiency; pnpase deficiency

• Autosomal recessive inheritance
• Intellectual disability
• Generalized hypotonia
• Ataxia
• Failure to thrive

SOURCES: SCTID NCIT OMIM ORPHANET DOID MESH GARD UMLS MONDO ICD10

Low match MACROCEPHALY/AUTISM SYNDROME

Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (Herman et al., 2007). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (Tsujita et al., 2016).

MACROCEPHALY/AUTISM SYNDROME Is also known as ;

• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Pica
• Hypertelorism

SOURCES: ORPHANET OMIM DOID UMLS MESH MONDO

Low match NIEMANN-PICK DISEASE, TYPE A

Niemann-Pick disease types A and B are caused by an inherited deficiency of acid sphingomyelinase activity. The clinical phenotype ranges from a severe infantile form with neurologic degeneration resulting in death usually by 3 years of age (type A) to a later-onset nonneurologic form (type B) that is compatible with survival into adulthood. Since intermediate cases also have been reported, the disease is best regarded a single entity with a clinical spectrum (summary by Schuchman, 2007).Knudson and Kaplan (1962) suggested that 3 types of the disorder can be distinguished: infantile cerebral, juvenile cerebral, and noncerebral. Later, 5 forms of Niemann-Pick disease were distinguished. Four were delineated by Crocker (1961): the classical infantile form (type A), the visceral form (type B), the subacute or juvenile form (type C; {257220}), and the Nova Scotian variant (type D; see {257220}). The fifth, the adult form (type E; see {607616}), was described by Terry et al. (1954) and Lynn and Terry (1964). Schneider et al. (1978) used the designation type F (see {607616}) for a form characterized in 2 patients by a thermolabile enzyme. Most patients fall into Crocker's group A, with death before age 3 years.Schuchman (2007) provided a detailed review of Niemann-Pick disease type A, including clinical management.

NIEMANN-PICK DISEASE, TYPE A Is also known as sphingomyelin lipidosis, sphingomyelinase deficiency;

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: UMLS GARD SCTID NCIT ORPHANET DOID ICD10 OMIM MESH MONDO

Low match NATURAL KILLER CELL AND GLUCOCORTICOID DEFICIENCY WITH DNA REPAIR DEFECT; NKGCD

Natural killer cell and glucocorticoid deficiency with DNA repair defect is an autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of NK cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer (summary by Gineau et al., 2012).

NATURAL KILLER CELL AND GLUCOCORTICOID DEFICIENCY WITH DNA REPAIR DEFECT; NKGCD Is also known as natural killer cell deficiency, familial isolated;nkcd;primary immunodeficiency due to mcm4 deficiency

• Autosomal recessive inheritance
• Global developmental delay
• Short stature
• Pica
• Microcephaly

SOURCES: MESH NCIT UMLS ORPHANET OMIM MONDO

Low match IMMUNODEFICIENCY 9; IMD9

Immunodeficiency-9 is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (summary by McCarl et al., 2009).

IMMUNODEFICIENCY 9; IMD9 Is also known as immune dysfunction with t-cell inactivation due to calcium entry defect 1;cid due to orai1 deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive

SOURCES: OMIM MESH MONDO GARD ORPHANET UMLS

Low match HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2; FHL2

Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG ) and TNF-alpha (OMIM ), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004).For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see {267700}.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2; FHL2 Is also known as hplh2, hlh2

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

SOURCES: GARD DOID OMIM UMLS MESH MONDO