Delayed speech and language development, and Blue sclerae

High match INTELLECTUAL DEVELOPMENTAL DISORDER WITH PERSISTENCE OF FETAL HEMOGLOBIN

Intellectual developmental disorder with persistence of fetal hemoglobin is characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin (HbF) (summary by Dias et al., 2016).Many of these features overlap with chromosome 2p16.1-p15 deletion syndrome (OMIM ).

INTELLECTUAL DEVELOPMENTAL DISORDER WITH PERSISTENCE OF FETAL HEMOGLOBIN Is also known as intellectual developmental disorder with hereditary persistence of fetal hemoglobin

• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Microcephaly
• Strabismus

SOURCES: MONDO OMIM UMLS

High match YOU-HOOVER-FONG SYNDROME; YHFS

YOU-HOOVER-FONG SYNDROME; YHFS Is also known as ;you-hoover-fong syndrome

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

SOURCES: UMLS OMIM ORPHANET MONDO

High match CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIB; ARCL3B

De Barsy syndrome, also known as autosomal recessive cutis laxa type III (ARCL3), is a rare autosomal recessive disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation (IUGR), and cutis laxa (summary by Lin et al., 2011).For a phenotypic description and a discussion of genetic heterogeneity of de Barsy syndrome, see {219150}.For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see {219200}.

CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIB; ARCL3B Is also known as de barsy syndrome b;pycr1 deficiency; pyrroline-5-carboxylate reductase 1 deficiency

• Autosomal recessive inheritance
• Intellectual disability
• Hypertelorism
• Cryptorchidism
• Flexion contracture

SOURCES: OMIM ORPHANET MONDO DOID UMLS

Medium match CLEFT PALATE, PSYCHOMOTOR RETARDATION, AND DISTINCTIVE FACIAL FEATURES; CPRF

Palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome is a rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, axial hypotonia, palate abnormalities (including cleft palate and/or high and narrow palate), dysmorphic facial features (including prominent forehead, hypertelorism, downslanting palpebral fissures, wide nasal bridge, thin lips and widely spaced teeth), and short stature. Additional manifestations may include digital anomalies (such as brachydactyly, clinodactyly, and hypoplastic toenails), a single palmar crease, lower limb hypertonia, joint hypermobility, as well as ocular and urogenital anomalies.

CLEFT PALATE, PSYCHOMOTOR RETARDATION, AND DISTINCTIVE FACIAL FEATURES; CPRF Is also known as ;palatal anomalies-multiple diastemata-facial dysmorphism-developmental delay syndrome

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: MONDO UMLS OMIM ORPHANET

Medium match ADAMS-OLIVER SYNDROME 2; AOS2

Adams-Oliver syndrome-2 is an autosomal recessive multiple congenital anomaly syndrome characterized by aplasia cutis congenita (ACC) and terminal transverse limb defects, in association with variable involvement of the brain, eyes, and cardiovascular systems (summary by Shaheen et al., 2011).For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (OMIM ).

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

SOURCES: UMLS OMIM MONDO

Medium match INSULIN-LIKE GROWTH FACTOR I, RESISTANCE TO; IGF1RES

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum).

INSULIN-LIKE GROWTH FACTOR I, RESISTANCE TO; IGF1RES Is also known as somatomedin, end-organ insensitivity to, somatomedin-c, resistance to, igf-i resistance;resistance to igf-1

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

SOURCES: ORPHANET OMIM MONDO UMLS GARD SCTID

Medium match CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A

De Barsy syndrome, or autosomal recessive cutis laxa type III (ARCL3), is characterized by cutis laxa, a progeria-like appearance, and ophthalmologic abnormalities (summary by Kivuva et al., 2008).For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see {219100}. Genetic Heterogeneity of de Barsy SyndromeAlso see ARCL3B (OMIM ), caused by mutation in the PYCR1 gene (OMIM ) on chromosome 17q25.

CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A Is also known as de barsy syndrome a, cutis laxa, corneal clouding, and mental retardation, progeroid syndrome of de barsy

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

SOURCES: MONDO OMIM DOID ORPHANET

Medium 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

Medium match OSTEOGENESIS IMPERFECTA, TYPE XV; OI15

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (OMIM ); perinatal lethal OI type II, also known as congenital OI (OMIM ); OI type III, a progressively deforming form with normal sclerae (OMIM ); and OI type IV, with normal sclerae (OMIM ). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (OMIM ) and COL1A2 (OMIM ). Keupp et al. (2013) and Pyott et al. (2013) described osteogenesis imperfecta type XV, an autosomal recessive form of the disorder characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclera. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.

OSTEOGENESIS IMPERFECTA, TYPE XV; OI15 Is also known as oi, type xv

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

SOURCES: DOID OMIM MONDO UMLS

Medium match COLE-CARPENTER SYNDROME 2; CLCRP2

• Autosomal recessive inheritance
• Short stature
• Pica
• Hypertelorism
• Motor delay

SOURCES: MONDO UMLS OMIM