Global developmental delay, and Recurrent fractures

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

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

• Global developmental delay
• Generalized hypotonia
• Muscle weakness
• Flexion contracture
• Peripheral neuropathy

SOURCES: OMIM MENDELIAN

Monosomy 5p, also known as Cri du chat syndrome, is a rare autosomal deletion syndrome characterized by a mewing cry (cri du chat) in infancy, multiple congenital anomalies, intellectual disability, microcephaly, and facial dysmorphism.

MONOSOMY 5P Is also known as cri du chat syndrome|deletion 5p

• Short stature
• Microcephaly
• Scoliosis
• Hypertelorism
• Muscular hypotonia

SOURCES: ORPHANET MENDELIAN

Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first months or years of life (summary by Knierim et al., 2016). Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone FracturesSee also SMABF2 (OMIM ), caused by mutation in the ASCC1 gene (OMIM ) on chromosome 10q22.

• Global developmental delay
• Generalized hypotonia
• Hypertelorism
• Muscle weakness
• Flexion contracture

SOURCES: OMIM MENDELIAN

Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis is a form of X-linked hypercalciuric nephrocalcinosis, a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see {300009}.

• Intellectual disability
• Short stature
• Generalized hypotonia
• Muscular hypotonia
• Pain

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

Osteopetrosis with renal tubular acidosis is a rare disorder characterized by osteopetrosis (see this term), renal tubular acidosis (RTA), and neurological disorders related to cerebral calcifications.

OSTEOPETROSIS WITH RENAL TUBULAR ACIDOSIS Is also known as mixed rta|mixed renal tubular acidosis|renal tubular acidosis type 3|rta, bicarbonate-wasting type|rta, dislocation type|guibaud-vainsel syndrome|carbonic anhydrase 2 deficiency|marble brain disease

• Intellectual disability
• Global developmental delay
• Failure to thrive
• Anemia
• Visual impairment

SOURCES: ORPHANET OMIM MENDELIAN

Osteoporosis pseudoglioma syndrome is a very rare autosomal recessive disorder characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures.

OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME Is also known as oppg|osteogenesis imperfecta, ocular form|ocular form of osteogenesis imperfecta|ops

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

SOURCES: OMIM MESH ORPHANET 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