Delayed speech and language development, and Congenital diaphragmatic hernia

Medium match MICROPHTHALMIA, SYNDROMIC 12; MCOPS12

MICROPHTHALMIA, SYNDROMIC 12; MCOPS12 Is also known as microphthalmia with or without pulmonary hypoplasia, diaphragmatic hernia, and/or cardiac defects

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Generalized hypotonia
• Micrognathia

SOURCES: MONDO GARD OMIM UMLS

Medium match GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; GCPS

Greig cephalopolysyndactyly syndrome is characterized by frontal bossing, scaphocephaly, and hypertelorism associated with pre- and postaxial polydactyly and variable syndactyly. The phenotype shows variable expressivity and can also include craniosynostosis. Affected individuals usually have normal psychomotor development (summary by Gorlin et al., 2001).

GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; GCPS Is also known as polysyndactyly with peculiar skull shape;gcps

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

SOURCES: NCIT ORPHANET UMLS OMIM DOID MONDO MESH GARD SCTID

Medium match MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 1; MCAHS1

Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age (summary by Maydan et al., 2011). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (OMIM ). Genetic Heterogeneity of Multiple Congenital Anomalies-Hypotonia-Seizures SyndromeMCAHS2 (OMIM ) is caused by mutation in the PIGA gene (OMIM ) on chromosome Xp22, and MCAHS3 (OMIM ) is caused by mutation in the PIGT gene (OMIM ) on chromosome 20q13.

MULTIPLE CONGENITAL ANOMALIES-HYPOTONIA-SEIZURES SYNDROME 1; MCAHS1 Is also known as glycosylphosphatidylinositol biosynthesis defect 3;gpibd3;congenital disorder of glycosylation due to pign deficiency; pign-cdg

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

SOURCES: MONDO DOID UMLS GARD OMIM ORPHANET

Medium match CHROMOSOME 15q26-qter DELETION SYNDROME

Distal monosomy 15q is a rare chromosomal anomaly syndrome characterized by pre- and postnatal growth restriction, developmental delay, variable degrees of intellectual disability, hand and foot anomalies (e.g. brachy-/clinodactyly, talipes equinovarus, nail hypoplasia, proximally placed digits) and mild craniofacial dysmorphism (incl. microcephaly, triangular face, broad nasal bridge, micrognathia). Neonatal lymphedema, heart malformations, aplasia cutis congenita, aortic root dilatation, and autistic spectrum disorder have also been reported.

CHROMOSOME 15q26-qter DELETION SYNDROME Is also known as drayer syndrome;15q26 deletion syndrome; distal 15q deletion syndrome; monosomy 15q26; telomeric 15q deletion syndrome

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

SOURCES: MONDO ORPHANET OMIM DOID MESH UMLS

Medium match CHROMOSOME 16p11.2 DELETION SYNDROME, 593-KB

The proximal 16p11.2 microdeletion syndrome is a chromosomal anomaly characterized by developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity.

CHROMOSOME 16p11.2 DELETION SYNDROME, 593-KB Is also known as ;proximal del(16)(p11.2); proximal monosomy 16p11.2

• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly
• Scoliosis

SOURCES: OMIM ORPHANET NCIT MONDO SCTID MESH GARD

Medium match WITTEVEEN-KOLK SYNDROME; WITKOS

15q24 microdeletion syndrome is a rare chromosomal anomaly characterized cytogenetically by a 1.7-6.1 Mb deletion in chromosome 15q24 and clinically by pre- and post-natal growth retardation, intellectual disability, distinct facial features, and genital, skeletal, and digital anomalies.

WITTEVEEN-KOLK SYNDROME; WITKOS Is also known as ;del(15)(q24); monosomy 15q24

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

SOURCES: OMIM UMLS ORPHANET SCTID MESH DOID MONDO GARD

Medium match CHROMOSOME 22q11.2 DELETION SYNDROME, DISTAL

Distal 22q11.2 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 22, with a highly variable phenotype characterized by prematurity, pre- and post-natal growth retardation, developmental delay (particularly speech), mild intellectual disability, variable cardiac defects, and minor skeletal anomalies (such as clinodactyly). Dysmorphic features include prominent forehead, arched eyebrows, deep set eyes, narrow upslanting palpebral fissures, ear abnormalities, hypoplastic alae nasi, smooth philtrum, down-turned mouth, thin upper lip, retro/micrognatia and pointed chin. For certain very distal deletions, there is a risk of developing malignant rhabdoid tumours.

CHROMOSOME 22q11.2 DELETION SYNDROME, DISTAL Is also known as distal chromosome 22q11.2 deletion syndrome;distal del(22)(q11.2); distal monosomy 22q11.2

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

SOURCES: MESH UMLS DOID OMIM MONDO ORPHANET

Low match COFFIN-SIRIS SYNDROME 1; CSS1

Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014). Mutations in the ARID1B gene are the most common cause of Coffin-Siris syndrome (Wieczorek et al., 2013). Genetic Heterogeneity of Coffin-Siris SyndromeForms of Coffin-Siris syndrome have been shown to be caused by mutations in genes encoding subunits of the SWI/SNF complex, also known as the BAF complex, which functions as a chromatin remodeling factor. These include CSS2 (OMIM ), caused by mutation in the ARID1A gene (OMIM ); CSS3 (OMIM ), caused by mutation in the SMARCB1 gene (OMIM ); CSS4 (OMIM ), caused by mutation in the SMARCA4 gene (OMIM ); CSS5 (OMIM ), caused by mutation in the SMARCE1 gene (OMIM ); and CSS6 (OMIM ), caused by mutation in the ARID2 gene (OMIM ).A similar phenotype, Nicolaides-Baraitser syndrome (NCBRS ), is also caused by mutation in a subunit of this complex, i.e., SMARCA2 (OMIM ).

COFFIN-SIRIS SYNDROME 1; CSS1 Is also known as coffin-siris syndrome;css, fifth digit syndrome, mental retardation, autosomal dominant 12;mrd12

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay

SOURCES: OMIM MONDO

Low match DIAPHRAGMATIC HERNIA, CONGENITAL

Congenital diaphragmatic hernia (CDH) refers to a group of congenital defects in the structural integrity of the diaphragm which are often associated with lethal pulmonary hypoplasia and pulmonary hypertension. Prevalence in newborns ranges from 1 in 2,500 to 1 in 4,000, and there is a 30 to 60% mortality rate (Langham et al., 1996; Harrison et al., 1994; Nobuhara et al., 1996). Most cases of congenital diaphragmatic hernia are sporadic. Genetic Heterogeneity of Diaphragmatic HerniaCongenital diaphragmatic hernia-1 (DIH1) maps to chromosome 15q26; DIH2 (OMIM ) maps to chromosome 8p23; and DIH3 (OMIM ) is associated with mutation in the ZFPM2 gene (OMIM ). There is evidence for further genetic heterogeneity, including a possible X-linked form (OMIM ).Congenital diaphragmatic hernia can also present with other congenital anomalies. Fryns syndrome (OMIM ) may be the most common autosomal recessive syndrome with DIH as a cardinal feature (Slavotinek et al., 2005).See Holder et al. (2007) for a review of genetic factors in congenital diaphragmatic hernia. Pober (2008) reviewed genetic aspects of congenital diaphragmatic hernia, with emphasis on various syndromes in which CDH occurs along with other manifestations.

DIAPHRAGMATIC HERNIA, CONGENITAL Is also known as dih, hernia, congenital diaphragmatic;hcd;cdh, diaphragmatic defect, congenital, diaphragm, unilateral agenesis of, hemidiaphragm, agenesis of;cdh

• Global developmental delay
• Hearing impairment
• Growth delay
• Atrial septal defect
• Respiratory distress

SOURCES: ORPHANET MONDO UMLS ICD10 SCTID OMIM

Low match CORNELIA DE LANGE SYNDROME 1; CDLS1

The Cornelia de Lange syndrome (CDLS) is a multisystem malformation syndrome recognized primarily on the basis of characteristic facial dysmorphism, including low anterior hairline, arched eyebrows, synophrys, anteverted nares, maxillary prognathism, long philtrum, thin lips, and 'carp' mouth, in association with prenatal and postnatal growth retardation, mental retardation and, in many cases, upper limb anomalies. However, there is wide clinical variability in this disorder, with milder phenotypes that may be difficult to ascertain on the basis of physical features (summary by Rohatgi et al., 2010).Boyle et al. (2015) provided a detailed review of CDLS, including clinical features, diagnosis, and genetic counseling. Genetic Heterogeneity of Cornelia de Lange SyndromeAbout 50 to 60% of the cases of CDLS are due to mutation in the NIPBL gene (Musio et al., 2006; Rohatgi et al., 2010).One X-linked form of CDLS (CDLS2 ) is caused by mutation in the SMC1A gene (OMIM ), which accounts for about 5% of cases. Two milder variants of Cornelia de Lange syndrome have been identified: CDLS3 (OMIM ), caused by mutation in the SMC3 gene (OMIM ), and CDLS4 (OMIM ), caused by mutation in the RAD21 gene (OMIM ). All 4 genes, NIPBL, SMC1A, SMC3, and RAD21, encode components of the cohesin complex. Another X-linked form, CDLS5 (OMIM ), is caused by mutation in the HDAC8 gene (OMIM ), the vertebrate histone deacetylase of SMC3.

CORNELIA DE LANGE SYNDROME 1; CDLS1 Is also known as cdl;cdls, typus degenerativus amstelodamensis, de lange syndrome, brachmann-de lange syndrome;bdls

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

SOURCES: NCIT OMIM