Delayed speech and language development, and Tetralogy of Fallot

Low match DUPLICATION/INVERSION 15Q11

The duplication/inversion 15q11 or isodicentric 15 chromosome (inv dup(15) or idic(15)) syndrome is a chromosomal disorder with distinctive clinical findings characterized by early central hypotonia, developmental delay and intellectual deficit, epilepsy, and autistic behavior.

DUPLICATION/INVERSION 15Q11 Is also known as invdup(15); isodicentric 15 chromosome; non-distal tetrasomy 15q; non-telomeric tetrasomy 15q; idic(15)

• Seizures
• Generalized hypotonia
• Microcephaly
• Growth delay
• Strabismus

SOURCES: MONDO UMLS ORPHANET MESH GARD

Low match CHROMOSOME 22q11.2 DUPLICATION SYNDROME

The newly described 22q11.2 microduplication syndrome (dup22q11 syndrome) is the association of a broad clinical spectrum and a duplication of the region that is deleted in patients with DiGeorge or velocardiofacial syndrome (DG/VCFS; see this term), establishing a complementary duplication syndrome.

CHROMOSOME 22q11.2 DUPLICATION SYNDROME Is also known as chromosome 22q11.2 microduplication syndrome;dup(22)(q11); duplication 22q11.2; trisomy 22q11.2

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

SOURCES: DOID MONDO ORPHANET GARD OMIM UMLS MESH SCTID

Low match KLEEFSTRA SYNDROME 1; KLEFS1

Submicroscopic subtelomeric deletions of chromosome 9q are associated with a recognizable mental retardation syndrome (Harada et al., 2004; Iwakoshi et al., 2004; Stewart et al., 2004; Neas et al., 2005). Common features in patients with 9q subtelomeric deletion syndrome are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, everted lower lip, carp mouth with macroglossia, and heart defects. Genetic Heterogeneity of Kleefstra SyndromeKLEFS2 (OMIM ) is caused by mutation in the KMT2C gene (OMIM ) on chromosome 7q36.

KLEEFSTRA SYNDROME 1; KLEFS1 Is also known as chromosome 9q34.3 deletion syndrome, 9q- syndrome, 9q subtelomeric deletion syndrome

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

SOURCES: DOID MONDO ORPHANET OMIM

Low match RENPENNING SYNDROME 1; RENS1

Renpenning syndrome is an X-linked mental retardation syndrome with clinically recognizable features. Affected individuals have microcephaly, short stature, small testes, and dysmorphic facies, including tall narrow face, upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. Stevenson et al. (2005) proposed that the various X-linked mental retardation syndromes due to PQBP1 mutations be combined under the name of Renpenning syndrome.

RENPENNING SYNDROME 1; RENS1 Is also known as mental retardation, x-linked, renpenning type, sutherland-haan x-linked mental retardation syndrome;shs, golabi-ito-hall syndrome, mental retardation, x-linked, with spastic diplegia, mental retardation, x-linked, syndromic 3;mrxs3, mental retardation, x-linked, syndromic 8;mrxs8, mental retardation, x-linked 55;mrx55

• Intellectual disability
• Seizures
• Short stature
• Hearing impairment
• Microcephaly

SOURCES: OMIM ORPHANET SCTID UMLS

Low match MOWAT-WILSON SYNDROME; MOWS

Mowat-Wilson syndrome is an autosomal dominant complex developmental disorder; individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. Mowat-Wilson syndrome has many clinical features in common with Goldberg-Shprintzen syndrome (OMIM ) but the 2 disorders are genetically distinct (Mowat et al., 2003). Goldberg-Shprintzen syndrome is caused by mutation in the KIAA1279 gene (OMIM ) located on 10q.

MOWAT-WILSON SYNDROME; MOWS Is also known as microcephaly, mental retardation, and distinct facial features, with or without hirschsprung disease, hirschsprung disease-mental retardation syndrome

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

SOURCES: SCTID ORPHANET OMIM UMLS

Low match ACROFACIAL DYSOSTOSIS 1, NAGER TYPE; AFD1

Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hypoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. The presence of anterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome (OMIM ), another rare AFD; however, distinguishing Nager syndrome from other AFDs, including Miller syndrome, can be challenging (summary by Bernier et al., 2012).

ACROFACIAL DYSOSTOSIS 1, NAGER TYPE; AFD1 Is also known as mandibulofacial dysostosis, treacher collins type, with limb anomalies, nager acrofacial dysostosis, afd, nager type, nager syndrome;mandibulofacial dysostosis with preaxial limb anomalies; nafd; nager acrofacial dysostosis; preaxial acrodysostosis

• Autosomal dominant inheritance
• Intellectual disability
• Short stature
• Pica
• Hearing impairment

SOURCES: ORPHANET SCTID GARD MONDO MESH UMLS OMIM DOID

Low match RITSCHER-SCHINZEL SYNDROME 1; RTSC1

The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay (summary by Leonardi et al., 2001; Seidahmed et al., 2011). Genetic Heterogeneity of Ritscher-Schinzel SyndromeSee also RTSC2 (OMIM ), caused by mutation in the CCDC22 gene (OMIM ) on chromosome Xp11.

RITSCHER-SCHINZEL SYNDROME 1; RTSC1 Is also known as craniocerebellocardiac dysplasia, 3c syndrome, dandy-walker-like malformation with atrioventricular septal defect;craniocerebellocardiac dysplasia; ritscher-schinzel syndrome

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

SOURCES: SCTID UMLS OMIM MONDO DOID ORPHANET

Low match VELOCARDIOFACIAL SYNDROME

VELOCARDIOFACIAL SYNDROME Is also known as chromosome 22q11.2 deletion syndrome, vcf syndrome;vcfs, shprintzen vcf syndrome

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

SOURCES: OMIM

Low match DIGEORGE SYNDROME; DGS

DiGeorge syndrome (DGS) comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and outflow tract defects of the heart. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. This deletion may present with a variety of phenotypes: Shprintzen, or velocardiofacial, syndrome (VCFS ); conotruncal anomaly face (or Takao syndrome); and isolated outflow tract defects of the heart including tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch. A collective acronym CATCH22 has been proposed for these differing presentations. A small number of cases of DGS have defects in other chromosomes, notably 10p13 (see {601362}). In the mouse, a transgenic Hox A3 (Hox 1.5) knockout produces a phenotype similar to DGS as do the teratogens retinoic acid and alcohol.

DIGEORGE SYNDROME; DGS Is also known as chromosome 22q11.2 deletion syndrome, hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome

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

SOURCES: OMIM

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