Immunodeficiency, and Overgrowth

Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.

PROPIONIC ACIDEMIA Is also known as glycinemia, ketotic|ketotic hyperglycinemia|propionyl-coa carboxylase deficiency|propionic aciduria|pcc deficiency|hyperglycinemia with ketoacidosis and leukopenia

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MESH MENDELIAN

Cowden syndrome (CS) is a difficult to recognize, under-diagnosed genodermatosis characterized by the presence of multiple hamartomas in various tissues and an increased risk for malignancies of the breast, thyroid, endometrium, kidney and colorectum. When CS is accompanied by germline PTEN mutations, it belongs to the PTEN hamartoma tumor syndrome (PHTS; see this term) group.

COWDEN SYNDROME Is also known as bzs|cowden disease|bbrs|macrocephaly, multiple lipomas, and hemangiomata|pten hamartoma tumor syndrome with granular cell tumor|bannayan-zonana syndrome|macrocephaly, pseudopapilledema, and multiple hemangiomata|cs|cd|mham|pten hamartoma tumor syndrome|ri

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Proteus syndrome (PS) is a very rare and complex hamartomatous overgrowth disorder characterized by progressive overgrowth of the skeleton, skin, adipose, and central nervous systems.

PROTEUS SYNDROME Is also known as partial gigantism-nevi-hemihypertrophy-macrocephaly syndrome|gigantism, partial, of hands and feet, nevi, hemihypertrophy, and macrocephaly

• Intellectual disability
• Seizures
• Scoliosis
• Hypertelorism
• Nystagmus

SOURCES: ORPHANET OMIM MESH MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Abnormal facial shape

SOURCES: OMIM MENDELIAN

Phelan-McDermid syndrome is a developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior (see {209850}), and minor dysmorphic features (Precht et al., 1998; Prasad et al., 2000; Durand et al., 2007).

PHELAN-MCDERMID SYNDROME; PHMDS Is also known as chromosome 22q13.3 deletion syndrome|telomeric 22q13 monosomy syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET MESH OMIM MENDELIAN

Alpha-mannosidosis is an autosomal recessive lysosomal storage disease characterized by mental retardation, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency. Expression of the disease varies considerably, and there is a wide spectrum of clinical findings and severity. Affected children are often normal at birth and during early development. They present in early childhood with delayed psychomotor development, delayed speech, and hearing loss. Additional features include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, dysostosis multiplex, and motor impairment (summary by Malm and Nilssen, 2008). Classification SystemsTwo classification systems have been used to describe the clinical presentation of alpha-mannosidosis. The earlier system delineated a more severe 'type I,' which shows infantile onset, rapid mental deterioration, hypotonia, splenomegaly, severe dysostosis multiplex, and severe recurrent infections, often resulting in death by age 8 years. Individuals with the less severe 'type II' show normal early development with later childhood development of mental retardation, hearing loss, coarse facies, neurologic deterioration, and survival well into adulthood (summary by Desnick et al., 1976 and Gotoda et al., 1998). A later classification system delineated 3 clinical types. Type 1 is the mildest form, with onset after age 10 years, without skeletal abnormalities and very slow progression. Type 2 is a moderate form, with onset before age 10 years, presence of skeletal abnormalities, and slow progression with development of ataxia by age 20 to 30 years. Type 3 is the severe form, with onset in early infancy, skeletal abnormalities, and obvious progression leading to early death from primary central nervous system involvement or myopathy. Most patients belong to clinical type 2 (summary by Malm and Nilssen, 2008). Despite the clinical heterogeneity of the disorder, there are no apparent genotype/phenotype correlations (Berg et al., 1999; Riise Stensland et al., 2012).

MANNOSIDOSIS, ALPHA B, LYSOSOMAL; MANSA Is also known as alpha-mannosidosis|lysosomal alpha-d-mannosidase deficiency|alpha-mannosidase b deficiency

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Scoliosis

SOURCES: ORPHANET OMIM MENDELIAN

Krakow-type spondyloepimetaphyseal dysplasia is characterized by severe skeletal dysplasia, severe immunodeficiency, and developmental delay (Csukasi et al., 2018).

SPONDYLOEPIMETAPHYSEAL DYSPLASIA, KRAKOW TYPE; SEMDK Is also known as immunoosseous dysplasia, krakow type

• Global developmental delay
• Neoplasm
• Immunodeficiency
• Skeletal dysplasia
• Rhizomelia

SOURCES: OMIM MENDELIAN

Facial dysmorphism-immunodeficiency-livedo-short stature syndrome is a rare genetic disease characterized by facial dysmorphism with malar hypoplasia and high forehead, immunodeficiency resulting in recurrent infections, impaired growth (with normal growth hormone production and response) resulting in short stature, and livedo affecting face and extremities. Immunological analyses show low memory B-cell and naïve T cell counts, decreased T cell proliferation, and reduced IgM, IgG2 and IgG4 titers. Patients do not exhibit increased susceptibility to cancer.

FACIAL DYSMORPHISM-IMMUNODEFICIENCY-LIVEDO-SHORT STATURE SYNDROME Is also known as fils syndrome

• Short stature
• Abnormal facial shape
• Pain
• Macrocephaly
• Malar flattening

SOURCES: ORPHANET OMIM MENDELIAN

Autoimmune lymphoproliferative syndrome (ALPS) with recurrent viral infections is a rare genetic disorder characterized by lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses.

AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME WITH RECURRENT VIRAL INFECTIONS Is also known as caspase 8 deficiency syndrome|autoimmune lymphoproliferative syndrome, type iib|alps2b|ceds|alps with recurrent viral infections

• Short stature
• Failure to thrive
• Splenomegaly
• Immunodeficiency
• Pneumonia

SOURCES: OMIM ORPHANET MENDELIAN

Primary immunodeficiency syndrome due to p14 deficiency is characterised by short stature, hypopigmentation, coarse facies and frequent bronchopulmonary Streptococcus pneumoniae infections.

PRIMARY IMMUNODEFICIENCY SYNDROME DUE TO P14 DEFICIENCY Is also known as primary immunodeficiency syndrome with short stature

• Short stature
• Immunodeficiency
• Coarse facial features
• Neutropenia
• Hypopigmentation of the skin

SOURCES: OMIM ORPHANET MESH MENDELIAN