Delayed speech and language development, and Bronchiectasis

High match ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH T-CELL IMMUNODEFICIENCY, AUTOSOMAL DOMINANT

Mutations in the NFKBIA gene result in functional impairment of NFKB1 (OMIM ), a master transcription factor required for normal activation of immune responses. Interruption of NFKB1 signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection (McDonald et al., 2007).

• Autosomal dominant inheritance
• Growth delay
• Failure to thrive
• Delayed speech and language development
• Tics

SOURCES: MESH MONDO OMIM UMLS

Medium 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

Medium match NEPHRONOPHTHISIS 15; NPHP15

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Nystagmus
• Abnormal facial shape

SOURCES: UMLS OMIM DOID MONDO

Medium 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

Medium match USHER SYNDROME, TYPE I; USH1

Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (OMIM ) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3 ) have progressive hearing loss. Genetic Heterogeneity of Usher Syndrome Type IUSH type I is genetically heterogeneous. USH1C (OMIM ), the 'Acadian variety,' is caused by mutation in harmonin (OMIM ), on 11p15. USH1D (OMIM ) is caused by mutation in the cadherin-23 (CDH23 ) on 10q21. USH1F (OMIM ) is caused by mutation in the protocadherin-15 (PCDH15 ) on 10q22. USH1G (OMIM ) is caused by mutation in the SANS gene (OMIM ), on 17q25. USH1E (OMIM ) maps to 21q21, and USH1H (OMIM ) maps to 15q22-q23. USH1J (OMIM ) is caused by mutation in the CIB2 gene (OMIM ) on 15q24. USH1K (OMIM ) maps to chromosome 10p11.21-q21.1.A form of USH type I in which affected members carried heterozygous mutations in both CDH23 and PCDH15 has been reported (USH1D/F; see {601067}), thus supporting a digenic model for some individuals with this phenotype.Gerber et al. (2006) presented evidence that the form of USH1 previously called USH1A, or the 'French variety,' and mapped to chromosome 14 does not in fact exist; mutations in the MYO7A gene were found in most of these families, and in others the phenotype was found to map to other loci.Ahmed et al. (2003) reviewed the molecular genetics of Usher syndrome and indicated that at least 12 loci had been identified as underlying the 3 different clinical subtypes.

USHER SYNDROME, TYPE I; USH1 Is also known as us1, retinitis pigmentosa and congenital deafness

• Autosomal recessive inheritance
• Intellectual disability
• Hearing impairment
• Ataxia
• Sensorineural hearing impairment

SOURCES: OMIM UMLS SCTID

Medium match PIGMENTARY DISORDER, RETICULATE, WITH SYSTEMIC MANIFESTATIONS, X-LINKED; PDR

X-linked reticulate pigmentary disorder shows more severe manifestations in hemizygous males compared to heterozygous females. Affected males have early onset of recurrent respiratory infections and failure to thrive resulting from inflammatory gastroenteritis or colitis. Patients also show reticular pigmentation abnormalities of the skin and may develop corneal scarring. Carrier females may be unaffected or have only pigmentary abnormalities along the lines of Blaschko (summary by Starokadomskyy et al., 2016).

PIGMENTARY DISORDER, RETICULATE, WITH SYSTEMIC MANIFESTATIONS, X-LINKED; PDR Is also known as xlpdr

• Intellectual disability
• Seizures
• Global developmental delay
• Pica
• Failure to thrive

SOURCES: MONDO OMIM

Medium match DEFICIENCY IN ANTERIOR PITUITARY FUNCTION-VARIABLE IMMUNODEFICIENCY SYNDROME

DEFICIENCY IN ANTERIOR PITUITARY FUNCTION-VARIABLE IMMUNODEFICIENCY SYNDROME Is also known as david syndrome

• Global developmental delay
• Failure to thrive
• Fatigue
• Alopecia
• Nail dystrophy

SOURCES: ORPHANET

Medium match IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 1; ICF1

Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency, and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients that is explained by mutations in the DNMT3B gene in some, but not all, ICF patients (Hagleitner et al., 2008). Genetic Heterogeneity of Immunodeficiency-Centromeric Instability-Facial Anomalies SyndromeSee also ICF2 (OMIM ), caused by mutation in the ZBTB24 gene (OMIM ) on chromosome 6q21; ICF3 (OMIM ), caused by mutation in the CDCA7 gene (OMIM ) on chromosome 2q31; and ICF4 (OMIM ), caused by mutation in the HELLS gene (OMIM ) on chromosome 10q23.

IMMUNODEFICIENCY-CENTROMERIC INSTABILITY-FACIAL ANOMALIES SYNDROME 1; ICF1 Is also known as immune deficiency, variable, with centromeric instability of chromosomes 1, 9, and 16, centromeric instability, immunodeficiency syndrome;ciid, immunodeficiency syndrome, variable

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Short stature
• Pica

SOURCES: OMIM SCTID DOID MONDO UMLS

Medium match IMMUNODEFICIENCY, COMMON VARIABLE, 10; CVID10

Common variable immunodeficiency-10 is an autosomal dominant primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency (summary by Chen et al., 2013).For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (OMIM ).

IMMUNODEFICIENCY, COMMON VARIABLE, 10; CVID10 Is also known as immunodeficiency, common variable, with central adrenal insufficiency, deficit in anterior pituitary function and variable immunodeficiency;david

• Autosomal dominant inheritance
• Global developmental delay
• Spasticity
• Gait disturbance
• Dysphagia

SOURCES: OMIM UMLS

Medium match IMMUNODEFICIENCY 23; IMD23

gene and characterized by neonatal to childhood onset of recurrent bacterial and viral infections, inflammatory skin diseases, atopic dermatitis and atopic diatheses, and marked serum IgE elevation. Early neurologic impairment is evident including developmental delay, intellectual disability, ataxia, dysarthria, sensorineural hearing loss, myoclonus and seizures.

IMMUNODEFICIENCY 23; IMD23 Is also known as immunodeficiency with hyper ige and cognitive impairment, immunodeficiency-vasculitis-myoclonus syndrome;ivms;cid due to pgm3 deficiency; combined immunodeficiency due to pgm3 deficiency; pgm3-related congenital disorder of glycosylation

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: MONDO GARD ORPHANET OMIM UMLS