Delayed speech and language development, and Iris coloboma

High match DEAFNESS, AUTOSOMAL RECESSIVE 108; DFNB108

• Hearing impairment
• Sensorineural hearing impairment
• Peripheral neuropathy
• Delayed speech and language development
• Coloboma

SOURCES: DOID OMIM MONDO

High match CATARACT 21, MULTIPLE TYPES; CTRCT21

Mutations in the MAF gene have been found to cause multiple types of cataract, which have been described as cortical pulverulent, lamellar, nuclear, nuclear pulverulent, nuclear stellate, anterior polar, anterior subcapsular, posterior subcapsular, and cerulean. In some cases, the cataracts are of juvenile onset.The preferred title of this entry was formerly 'Cataract, Pulverulent, Juvenile-Onset,' with an 'Included' title/symbol of 'Cataract, Congenital, Cerulean Type, 4; CCA4.'

CATARACT 21, MULTIPLE TYPES; CTRCT21 Is also known as cataract 21, multiple types, with or without microcornea, cataract, congenital, cerulean type, 4;cca4, cataract, pulverulent, juvenile-onset

• Autosomal dominant inheritance
• Cataract
• Delayed speech and language development
• Atrial septal defect
• Microphthalmia

SOURCES: UMLS OMIM DOID MONDO MESH

High match DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY

Dihyropyrimidine dehydrogenase deficiency shows large phenotypic variability, ranging from no symptoms to a convulsive disorder with motor and mental retardation in homozygous patients. In addition, homozygous and heterozygous mutation carriers can develop severe toxicity after the administration of the antineoplastic drug 5-fluorouracil (5FU), which is also catabolized by the DPYD enzyme. This is an example of a pharmacogenetic disorder (Van Kuilenburg et al., 1999).Since there is no correlation between genotype and phenotype in DPD deficiency, it appears that the deficiency is a necessary, but not sufficient, prerequisite for the development of clinical abnormalities (Van Kuilenburg et al., 1999; Enns et al., 2004).

DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY Is also known as dpd deficiency, dpyd deficiency, thymine-uraciluria, hereditary, pyrimidinemia, familial;familial pyrimidinemia

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

SOURCES: NCIT ORPHANET MONDO MESH OMIM DOID GARD SCTID

High match MENTAL RETARDATION, AUTOSOMAL DOMINANT 20; MRD20

MENTAL RETARDATION, AUTOSOMAL DOMINANT 20; MRD20 Is also known as mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations

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

SOURCES: UMLS DOID OMIM MONDO

Medium match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id; CDG1D

Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006).CDG1D is a type I CDG that generally presents with severe neurologic involvement associated with dysmorphism and visual impairment. Liver involvement is sometimes present (summary by Marques-da-Silva et al., 2017).For a discussion of the classification of CDGs, see CDG1A (OMIM ).

CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id; CDG1D Is also known as cdg id;cdgid, carbohydrate-deficient glycoprotein syndrome, type iv, formerly;cdgs4, formerly, cdgs, type iv, formerly;cdg syndrome type id; cdg-id; cdg1d; carbohydrate deficient glycoprotein syndrome type id; congenital disorder of glycosylation type 1d; congenital disorder of glycosylation type id; mannosyltransferase 6 deficiency

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

SOURCES: UMLS MESH NCIT GARD SCTID ORPHANET OMIM MONDO

Medium match CHROMOSOME 17q11.2 DELETION SYNDROME, 1.4-MB

Approximately 5 to 20% of all patients with neurofibromatosis type I (OMIM ) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003).

CHROMOSOME 17q11.2 DELETION SYNDROME, 1.4-MB Is also known as neurofibromatosis 1 microdeletion syndrome, nf1 microdeletion syndrome, van asperen syndrome;dup(17)(q11.2); grisart-destrée syndrome; trisomy 17q11.2

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

SOURCES: GARD ORPHANET DOID OMIM MONDO

Medium match HELSMOORTEL-VAN DER AA SYNDROME; HVDAS

HELSMOORTEL-VAN DER AA SYNDROME; HVDAS Is also known as mental retardation, autosomal dominant 28;mrd28;

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

SOURCES: MONDO GARD DOID OMIM ORPHANET UMLS

Medium match CHROMOSOME 13q14 DELETION SYNDROME

Monosomy 13q14 is a rare chromosomal anomaly syndrome, resulting from a partial deletion of the long arm of chromosome 13, characterized by developmental delay, variable degrees of intellectual disability, retinoblastoma and craniofacial dysmorphism (incl. micro/dolichocephaly, high and broad forehead, prominent eyebrows, thick, anteverted ear lobes, short nose with a broad nasal bridge and bulbous tip, prominent philtrum, large mouth with thin upper lip and thick, everted lower lip). Other features reported include high birth weight, macrocephaly, pinealoma, hepatomegaly, inguinal hernia and cryptorchidism.

CHROMOSOME 13q14 DELETION SYNDROME Is also known as chromosome 13q deletion syndrome;del(13)(q14); deletion 13q14

• Autosomal dominant inheritance
• Intellectual disability
• Short stature
• Generalized hypotonia
• Pica

SOURCES: MONDO UMLS MESH NCIT ORPHANET OMIM DOID

Medium match ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL

Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007).The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).

ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; ECCL Is also known as ;haberland syndrome

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

SOURCES: ORPHANET SCTID MESH GARD OMIM UMLS MONDO NCIT

Medium match BARDET-BIEDL SYNDROME 1; BBS1

Bardet-Biedl syndrome is an autosomal recessive and genetically heterogeneous ciliopathy characterized by retinitis pigmentosa, obesity, kidney dysfunction, polydactyly, behavioral dysfunction, and hypogonadism (summary by Beales et al., 1999). Eight proteins implicated in the disorder assemble to form the BBSome, a stable complex involved in signaling receptor trafficking to and from cilia (summary by Scheidecker et al., 2014). Genetic Heterogeneity of Bardet-Biedl SyndromeBBS1 is caused by mutation in a gene on chromosome 11q13 (OMIM ); BBS2 (OMIM ), by mutation in a gene on 16q13 (OMIM ); BBS3 (OMIM ), by mutation in the ARL6 gene on 3q11 (OMIM ); BBS4 (OMIM ), by mutation in a gene on 15q22 (OMIM ); BBS5 (OMIM ), by mutation in a gene on 2q31 (OMIM ); BBS6 (OMIM ), by the MKKS gene on 20p12 (OMIM ), mutations in which also cause McKusick-Kaufman syndrome (OMIM ); BBS7 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS8 (OMIM ), by mutation in the TTC8 gene on 14q32 (OMIM ); BBS9 (OMIM ), by mutation in a gene on 7p14 (OMIM ); BBS10 (OMIM ), by mutation in a gene on 12q (OMIM ); BBS11 (OMIM ), by mutation in the TRIM32 gene on 9q33 (OMIM ); BBS12 (OMIM ), by mutation in a gene on 4q27 (OMIM ); BBS13 (OMIM ), by mutation in the MKS1 gene (OMIM ) on 17q23, mutations in which also cause Meckel syndrome-1 (OMIM ); BBS14 (OMIM ), by mutation in the CEP290 gene (OMIM ) on 12q21, mutations in which also cause Meckel syndrome-4 (OMIM ) and several other disorders; BBS15 (OMIM ), by mutation in the C2ORF86 gene (OMIM ), which encodes a homolog of the Drosophila planar cell polarity gene 'fritz,' on 2p15; BBS16 (OMIM ), by mutation in the SDCCAG8 gene (OMIM ) on 1q43, mutations in which also cause Senior-Loken syndrome-7 (OMIM ); BBS17 (OMIM ), by mutation in the LZTFL1 gene (OMIM ) on 3p21; BBS18 (OMIM ), by mutation in the BBIP1 gene (OMIM ) on 10q25; BBS19 (OMIM ), by mutation in the IFT27 gene (OMIM ) on 22q12; BBS20 (OMIM ), by mutation in the IFT74 gene (OMIM ) on 9p21; and BBS21 (OMIM ), by mutation in the C8ORF37 gene (OMIM ).The CCDC28B gene (OMIM ) modifies the expression of BBS phenotypes in patients who have mutations in other genes. Mutations in MKS1, MKS3 (TMEM67 ), and C2ORF86 also modify the expression of BBS phenotypes in patients who have mutations in other genes.Although BBS had originally been thought to be a recessive disorder, Katsanis et al. (2001) demonstrated that clinical manifestation of some forms of Bardet-Biedl syndrome requires recessive mutations in 1 of the 6 loci plus an additional mutation in a second locus. While Katsanis et al. (2001) called this 'triallelic inheritance,' Burghes et al. (2001) suggested the term 'recessive inheritance with a modifier of penetrance.' Mykytyn et al. (2002) found no evidence of involvement of the common BBS1 mutation in triallelic inheritance. However, Fan et al. (2004) found heterozygosity in a mutation of the BBS3 gene ({608845.0002}) as an apparent modifier of the expression of homozygosity of the met390-to-arg mutation in the BBS1 gene ({209901.0001}).Allelic disorders include nonsyndromic forms of retinitis pigmentosa: RP51 (OMIM ), caused by TTC8 mutation, and RP55 (OMIM ), caused by ARL6 mutation.

• Autosomal recessive inheritance
• Intellectual disability
• Global developmental delay
• Pica
• Hearing impairment

SOURCES: OMIM UMLS DOID MESH MONDO GARD EFO