Global developmental delay, and Blue sclerae

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

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Scoliosis

SOURCES: OMIM MENDELIAN

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 dias-logan syndrome|intellectual developmental disorder with hereditary persistence of fetal hemoglobin

• Intellectual disability
• Global developmental delay
• Microcephaly
• Strabismus
• Low-set ears

SOURCES: OMIM MENDELIAN

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 ). Cabral et al. (2007) described a form of autosomal recessive OI, which they designated OI type VIII, characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses.

OSTEOGENESIS IMPERFECTA, TYPE VIII; OI8 Is also known as oi, type viii

• Global developmental delay
• Scoliosis
• Growth delay
• Kyphosis
• Inguinal hernia

SOURCES: OMIM MESH MENDELIAN

The features of Ehlers-Danlos syndrome spondylodysplastic type 2 include an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin (Okajima et al., 1999).For a discussion of genetic heterogeneity of the spondylodysplastic type of Ehlers-Danlos syndrome, see {130070}.

EHLERS-DANLOS SYNDROME, SPONDYLODYSPLASTIC TYPE, 2; EDSSPD2 Is also known as ehlers-danlos syndrome, progeroid type, 2, formerly|edsp2, formerly

• Global developmental delay
• Short stature
• Generalized hypotonia
• Cleft palate
• Talipes equinovarus

SOURCES: OMIM MENDELIAN

TELO2-RELATED INTELLECTUAL DISABILITY-NEURODEVELOPMENTAL DISORDER Is also known as you-hoover-fong syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 26 Is also known as coxpd26

• Global developmental delay
• Generalized hypotonia
• Growth delay
• Failure to thrive
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

Osteogenesis imperfecta type XVIII (OI18) is characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life (Doyard et al., 2018).

• Global developmental delay
• Generalized hypotonia
• Micrognathia
• Delayed speech and language development
• Motor delay

SOURCES: OMIM MENDELIAN

The musculocontractural type of Ehlers-Danlos syndrome is characterized by progressive multisystem fragility-related manifestations, including joint dislocations and deformities; skin hyperextensibility, bruisability, and fragility, with recurrent large subcutaneous hematomas; cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications; and myopathy, featuring muscle hypoplasia, muscle weakness, and an abnormal muscle fiber pattern in histology in adulthood, resulting in gross motor developmental delay (summary by Muller et al., 2013).For a discussion of genetic heterogeneity of the musculocontractural type of Ehlers-Danlos syndrome, see EDSMC1 (OMIM ).

• Global developmental delay
• Hypertelorism
• Muscle weakness
• Abnormal facial shape
• Pain

SOURCES: OMIM MENDELIAN

Autosomal recessive cutis laxa type 2B is a rare, hereditary, developmental defect with connective tissue involvement characterized by cutis laxa of variable severity, in utero growth restriction, congenital hip dislocation and joint hyperlaxity, wrinkling of the skin, in particular the dorsum of hands and feet, and progeroid facial features. Hypotonia, developmental delay, and intellectual disability are common. In addition, cataracts, corneal clouding, wormian bones, lipodystrophy and osteopenia have been reported.

AUTOSOMAL RECESSIVE CUTIS LAXA TYPE 2B Is also known as autosomal recessive cutis laxa type 2, progeroid type|cutis laxa with progeroid features|arcl2, progeroid type|arcl2b

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

SOURCES: OMIM ORPHANET MESH MENDELIAN

Cole-Carpenter syndrome is an extremely rare form of bone dysplasia characterized by the features of osteogenesis imperfecta such as bone fragility associated with multiple fractures, bone deformities (metaphyseal irregularities and bowing of the long bones) and blue sclera, in association with growth failure, craniosynostosis, hydrocephalus, ocular proptosis, and distinctive facial features (e.g. frontal bossing, midface hypoplasia, and micrognathia).

COLE-CARPENTER SYNDROME Is also known as bone fragility-craniosynostosis-proptosis-hydrocephalus syndrome|bone fragility with craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features

• Global developmental delay
• Short stature
• Generalized hypotonia
• Scoliosis
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN