Delayed speech and language development, and Atopic dermatitis

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

Medium match NETHERTON SYNDROME; NETH

Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002).

NETHERTON SYNDROME; NETH Is also known as erythroderma, ichthyosiform, with hypotrichosis and hyper-ige, ns, netherton disease, comel-netherton syndrome;bamboo hair syndrome; comèl-netherton syndrome; ns

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

SOURCES: NCIT ORPHANET MONDO SCTID OMIM

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

Medium match EVEN-PLUS SYNDROME; EVPLS

EVEN-PLUS syndrome is characterized by prenatal-onset short stature, vertebral and epiphyseal changes, microtia, midface hypoplasia with flat nose and triangular nares, cardiac malformations, and other findings including anal atresia, hypodontia, and aplasia cutis. The features overlap those reported in patients with CODAS syndrome ({600373}; Royer-Bertrand et al., 2015).

EVEN-PLUS SYNDROME; EVPLS Is also known as epiphyseal and vertebral dysplasia, microtia, and flat nose, plus associated malformations;epiphysial-vertebral-ear dysplasia-nose-plus associated findings syndrome

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

SOURCES: OMIM UMLS MONDO ORPHANET

Low match CARDIOFACIOCUTANEOUS SYNDROME 1; CFC1

Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects, and mental retardation (summary by Niihori et al., 2006). The heart defects include pulmonic stenosis, atrial septal defect, and hypertrophic cardiomyopathy. Some patients have ectodermal abnormalities such as sparse and friable hair, hyperkeratotic skin lesions, and a generalized ichthyosis-like condition. Typical facial characteristics include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Most cases occur sporadically, but autosomal dominant transmission has been rarely reported (Linden and Price, 2011).Roberts et al. (2006) provided a detailed review of CFC syndrome, including a discussion of the phenotypic overlap of CFC syndrome with Noonan syndrome (NS1 ) and Costello syndrome (OMIM ). Genetic Heterogeneity of Cardiofaciocutaneous SyndromeOther forms of cardiofaciocutaneous syndrome include CFC2 (OMIM ), caused by mutation in the KRAS gene (OMIM ); CFC3 (OMIM ), caused by mutation in the MAP2K1 gene (OMIM ); and CFC4 (OMIM ), caused by mutation in the MAP2K2 gene (OMIM ). The protein products of these causative genes, including BRAF, interact in a common RAS/ERK (see {601795}) pathway that regulates cell differentiation, proliferation, and apoptosis (summary by Roberts et al., 2006).

CARDIOFACIOCUTANEOUS SYNDROME 1; CFC1 Is also known as cfc syndrome, cfcs;cfc syndrome

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

SOURCES: UMLS ORPHANET SCTID MONDO OMIM

Low match IMMUNODEFICIENCY, DEVELOPMENTAL DELAY, AND HYPOHOMOCYSTEINEMIA; IMDDHH

IMDDHH is a multisystem disorder characterized by immunodeficiency, mildly delayed psychomotor development, poor overall growth from infancy, and hypohomocysteinemia. Additional features, such as congenital heart defects and liver involvement, are more variable (summary by Huppke et al., 2017).

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Pica

SOURCES: OMIM

Low match ROLANDIC EPILEPSY, MENTAL RETARDATION, AND SPEECH DYSPRAXIA, X-LINKED; RESDX

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Delayed speech and language development
• Hyperreflexia

SOURCES: MESH MONDO OMIM UMLS

Low match MENTAL RETARDATION, AUTOSOMAL DOMINANT 7; MRD7

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Generalized hypotonia
• Microcephaly

SOURCES: UMLS ORPHANET OMIM

Low match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE If; CDG1F

Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin. For a general discussion of CDGs, see CDG Ia (OMIM ) and CDG Ib (OMIM ).

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE If; CDG1F Is also known as cdg if;cdgif;cdg syndrome type if; cdg-if; cdg1f; carbohydrate deficient glycoprotein syndrome type if; congenital disorder of glycosylation type 1f; congenital disorder of glycosylation type if

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

SOURCES: MESH GARD UMLS NCIT MONDO SCTID OMIM ORPHANET

Low match IMMUNODEFICIENCY 49; IMD49

IMMUNODEFICIENCY 49; IMD49 Is also known as severe combined immunodeficiency, t cell-negative, b cell-positive, nk cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities, scid, t cell-negative, b cell-positive, nk cell-positive, with intellectual disability, spasticity, and craniofacial abnormalities

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

SOURCES: UMLS MONDO OMIM