Delayed speech and language development, and Neuroblastoma

Medium match SKIN CREASES, CONGENITAL SYMMETRIC CIRCUMFERENTIAL, 1; CSCSC1

Congenital symmetric circumferential skin creases is characterized by the folding of excess skin, which leads to ringed creases, primarily of the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features (summary by Isrie et al., 2015). Genetic Heterogeneity of Congenital Symmetric Circumferential Skin CreasesCSCSC2 (OMIM ) is caused by mutation in the MAPRE2 gene (OMIM ) on chromosome 18q12.

SKIN CREASES, CONGENITAL SYMMETRIC CIRCUMFERENTIAL, 1; CSCSC1 Is also known as skin creases, multiple benign ring-shaped, of limbs, circumferential skin creases, kunze type, michelin tire baby syndrome;ccsf; circumferential skin creases, kunze type; congenital circumferential skin folds; kunze-riehm syndrome

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

SOURCES: ORPHANET OMIM UMLS SCTID

Low match ACHONDROPLASIA; ACH

Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by Bellus et al., 1995).

• Autosomal dominant inheritance
• Short stature
• Generalized hypotonia
• Pica
• Hearing impairment

SOURCES: ICD10 NCIT DOID MESH GARD MONDO OMIM

Low match SOTOS SYNDROME 1; SOTOS1

SOTOS SYNDROME 1; SOTOS1 Is also known as sotos syndrome, cerebral gigantism, chromosome 5q35 deletion syndrome

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

SOURCES: NCIT MONDO OMIM

Low match CHROMOSOME 1p36 DELETION SYNDROME

The constitutional deletion of chromosome 1p36 results in a syndrome with multiple congenital anomalies and mental retardation (Shapira et al., 1997). Monosomy 1p36 is the most common terminal deletion syndrome in humans, occurring in 1 in 5,000 births (Shaffer and Lupski, 2000; Heilstedt et al., 2003).See also neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH ), which shows overlapping features and is caused by heterozygous mutation in the RERE gene (OMIM ) on proximal chromosome 1p36.

CHROMOSOME 1p36 DELETION SYNDROME Is also known as monosomy 1p36 syndrome;del(1)(p36); deletion 1p36; deletion 1pter; monosomy 1p36; monosomy 1pter; subtelomeric 1p36 deletion

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

SOURCES: GARD UMLS ORPHANET MONDO SCTID DOID OMIM NCIT MESH

Low match WEAVER SYNDROME; WVS

Weaver syndrome comprises pre- and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance, and developmental delay. Most cases are sporadic, although autosomal dominant inheritance has been reported. Although there is phenotypic overlap between Weaver syndrome and Sotos syndrome (OMIM ), distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand in Weaver syndrome, whereas in Sotos syndrome carpal bone development is at or behind that of the rest of the hand (summary by Basel-Vanagaite, 2010).The 'Weaver-like' syndrome reported by Stoll et al. (1985) in a mother and son may be a separate entity.Sotos syndrome (OMIM ), which shows considerable phenotypic overlap with Weaver syndrome, is caused by mutation in the NSD1 gene (OMIM ) on chromosome 5q35.

WEAVER SYNDROME; WVS Is also known as weaver-smith syndrome;wss

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

SOURCES: OMIM ORPHANET

Low match COSTELLO SYNDROME; CSTLO

Costello syndrome is a rare multiple congenital anomaly syndrome associated in all cases with a characteristic coarse facies, short stature, distinctive hand posture and appearance, severe feeding difficulty, and failure to thrive. Other features include cardiac anomalies and developmental disability. Facial warts, particularly nasolabial, are often present in childhood (Kerr et al., 2006).In patients with a clinical diagnosis of Costello syndrome, Zenker et al. (2007) identified mutations in the KRAS gene, but noted that these patients may later develop features of CFC syndrome. In either case, the findings underscore the central role of Ras in the pathogenesis of these phenotypically related disorders (Zenker et al., 2007). However, Kerr et al. (2008) commented that the diagnosis of Costello syndrome should only be used to refer to patients with mutations in the HRAS gene.

COSTELLO SYNDROME; CSTLO Is also known as faciocutaneoskeletal syndrome, fcs syndrome;fcs syndrome; faciocutaneoskeletal syndrome

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

SOURCES: DOID OMIM MONDO GARD SCTID ORPHANET MESH UMLS NCIT

Low match RUBINSTEIN-TAYBI SYNDROME 1; RSTS1

Rubinstein-Taybi syndrome is a multiple congenital anomaly syndrome characterized by mental retardation, postnatal growth deficiency, microcephaly, broad thumbs and halluces, and dysmorphic facial features. The facial appearance is striking, with highly arched eyebrows, long eyelashes, downslanting palpebral fissures, broad nasal bridge, beaked nose with the nasal septum, highly arched palate, mild micrognathia, and characteristic grimacing or abnormal smile. Affected individuals also have an increased risk of tumor formation (Rubinstein and Taybi, 1963; review by Hennekam, 2006).Floating-Harbor syndrome (OMIM ), which shows phenotypic overlap with Rubinstein-Taybi syndrome, is caused by mutation in the SRCAP gene (OMIM ), a coactivator for CREBBP. Genetic Heterogeneity of Rubinstein-Taybi SyndromeRubinstein-Taybi syndrome-1 (RSTS1) constitutes about 50 to 70% of patients with the disorder. Rubinstein-Taybi syndrome-2 (RSTS2 ) comprises about 3% of patients and is primarily due to de novo heterozygous mutation in the EP300 gene (OMIM ) on chromosome 22q13 (Bartsch et al., 2010).See also chromosome 16p13.3 deletion syndrome (OMIM ), a severe form of Rubinstein-Taybi syndrome resulting from a contiguous gene deletion involving the CREBBP gene as well as other neighboring genes.

RUBINSTEIN-TAYBI SYNDROME 1; RSTS1 Is also known as rubinstein syndrome, broad thumbs and great toes, characteristic facies, and mental retardation, broad thumb-hallux syndrome

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

SOURCES: OMIM

Low match LEOPARD SYNDROME 1; LPRD1

LEOPARD is an acronym for the manifestations of this syndrome as listed by Gorlin et al. (1969): multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. Genetic Heterogeneity of LEOPARD SyndromeLEOPARD syndrome is a genetically heterogeneous disorder. See also LEOPARD syndrome-2 (OMIM ), caused by mutation in the RAF1 gene (OMIM ), and LEOPARD syndrome-3 (OMIM ), caused by mutation in the BRAF gene (OMIM ).

LEOPARD SYNDROME 1; LPRD1 Is also known as lentiginosis, cardiomyopathic, multiple lentigines syndrome;cardiomyopathic lentiginosis; familial multiple lentigines syndrome; leopard syndrome

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

SOURCES: SCTID OMIM ORPHANET UMLS

Low match HADDAD SYNDROME

Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS), or Ondine syndrome, occurs concurrently with Hirschsprung disease (see these terms).

HADDAD SYNDROME Is also known as congenital central alveolar hypoventilation-hirschsprung disease syndrome; ondine-hirschsprung disease; ondine-hirschsprung syndrome

• Intellectual disability
• Seizures
• Strabismus
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: ORPHANET SCTID

Low match NIJMEGEN BREAKAGE SYNDROME; NBS

The Nijmegen breakage syndrome and the phenotypically indistinguishable Berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. Ataxia-telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2 is the designation for the Berlin breakage syndrome, which differ only in complementation studies. Cells from NBS/BBS patients are hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia (AT ), but NBS/BBS patients have a distinct clinical phenotype.The clinical features of LIG4 syndrome (OMIM ), caused by mutation in the LIG4 gene (OMIM ), resemble those of NBS.

NIJMEGEN BREAKAGE SYNDROME; NBS Is also known as ataxia-telangiectasia variant v1;at-v1, microcephaly with normal intelligence, immunodeficiency, and lymphoreticular malignancies, seemanova syndrome ii, nonsyndromal microcephaly, autosomal recessive, with normal intelligence, immunodeficiency, microcephaly, and chromosomal instability;at v1; ataxia-telangiectasia, variant 1; berlin breakage syndrome; immunodeficiency-microcephaly-chromosomal instability syndrome; microcephaly-immunodeficiency-lymphoreticuloma syndrome; nbs; seemanova syndrome type 2

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

SOURCES: ORPHANET DOID NCIT MESH GARD MONDO SCTID OMIM UMLS