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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. , retinal detachment, moderate sensorineural hearing loss, and proteinuria without aminoaciduria. Facial features included prominent brow, flat nasal bridge, hypertelorism, and downslanting palpebral fissures. In contrast to the previously reported patients, he had normal intellect and was learning Braille. Devriendt et al. (1998) reported a male infant with hypertelorism, severe myopia, sensorineural deafness, diaphragmatic hernia, and proteinuria. Other features included large anterior fontanel, depressed nasal bridge, downslanting palpebral fissures, and delayed development. The proteinuria was nonselective and did not include glucose or amino acids. Although the child did not have agenesis of the corpus callosum or exomphalos, the authors concluded that FOAR and Donnai-Barrow syndrome are the same entity. Devriendt et al. (1998) postulated that the brothers reported by Ohlsson ( | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. and proteinuria. Other features included large anterior fontanel, depressed nasal bridge, downslanting palpebral fissures, and delayed development. The proteinuria was nonselective and did not include glucose or amino acids. Although the child did not have agenesis of the corpus callosum or exomphalos, the authors concluded that FOAR and Donnai-Barrow syndrome are the same entity. Devriendt et al. (1998) postulated that the brothers reported by Ohlsson (1963) may have had the same syndrome. Avunduk et al. (2000) reported a male child, born of consanguineous parents, who had exomphalos, agenesis of the corpus callosum, right iris coloboma, high myopia, retinal anomalies, and sensorineural deafness. Facial features included prominent forehead, long nose, downslanting palpebral fissures, and hypertelorism. There was no evidence | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. that the brothers reported by Ohlsson (1963) may have had the same syndrome. Avunduk et al. (2000) reported a male child, born of consanguineous parents, who had exomphalos, agenesis of the corpus callosum, right iris coloboma, high myopia, retinal anomalies, and sensorineural deafness. Facial features included prominent forehead, long nose, downslanting palpebral fissures, and hypertelorism. There was no evidence of diaphragmatic hernia or heart defects. The authors noted the striking similarities to the patients reported by Donnai and Barrow (1993). The report confirmed autosomal recessive inheritance. Chassaing et al. (2003) reported Donnai-Barrow syndrome in 2 sets of sibs and in an unrelated child, with features including diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. and hypertelorism. There was no evidence of diaphragmatic hernia or heart defects. The authors noted the striking similarities to the patients reported by Donnai and Barrow (1993). The report confirmed autosomal recessive inheritance. Chassaing et al. (2003) reported Donnai-Barrow syndrome in 2 sets of sibs and in an unrelated child, with features including diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness. Kantarci et al. (2007) reported follow-up of 1 affected girl reported by Chassaing et al. (2003). At age 6 years, she was legally blind with mild developmental delay, but was learning Braille. She had a nonacidotic proximal tubulopathy. Kantarci et al. (2007) reported a large consanguineous family from the United Arab Emirates in which 5 | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. hypertelorism, myopia, and sensorineural deafness. Kantarci et al. (2007) reported follow-up of 1 affected girl reported by Chassaing et al. (2003). At age 6 years, she was legally blind with mild developmental delay, but was learning Braille. She had a nonacidotic proximal tubulopathy. Kantarci et al. (2007) reported a large consanguineous family from the United Arab Emirates in which 5 sibs had Donnai-Barrow syndrome. The proband had characteristic cranial features and died of complications of congenital diaphragmatic hernia. Four surviving sibs had variable clinical features, including diaphragmatic eventration with pulmonary hypoplasia, omphalocele, sensorineural deafness, agenesis of the corpus callosum, hypertelorism, high myopia, large anterior fontanel, and developmental delay. One child also had retinal dystrophy, scoliosis, rib and vertebral anomalies, and short | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. from the United Arab Emirates in which 5 sibs had Donnai-Barrow syndrome. The proband had characteristic cranial features and died of complications of congenital diaphragmatic hernia. Four surviving sibs had variable clinical features, including diaphragmatic eventration with pulmonary hypoplasia, omphalocele, sensorineural deafness, agenesis of the corpus callosum, hypertelorism, high myopia, large anterior fontanel, and developmental delay. One child also had retinal dystrophy, scoliosis, rib and vertebral anomalies, and short sternum. Imaging of 1 child showed numerous brain anomalies, including partially empty sella turcica, small pons, periventricular nodular heterotopia, small optic nerves and chiasm, ocular colobomas, and malformation of the left horizontal semicircular canal and vestibule. Urine samples from affected individuals showed proteinuria with spillage of retinol-binding proteins (see RBP1, 180260) and vitamin D-binding proteins (see DBP | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. , scoliosis, rib and vertebral anomalies, and short sternum. Imaging of 1 child showed numerous brain anomalies, including partially empty sella turcica, small pons, periventricular nodular heterotopia, small optic nerves and chiasm, ocular colobomas, and malformation of the left horizontal semicircular canal and vestibule. Urine samples from affected individuals showed proteinuria with spillage of retinol-binding proteins (see RBP1, 180260) and vitamin D-binding proteins (see DBP, 139200).
Inheritance
Donnai-Barrow syndrome usually shows an autosomal recessive mode of inheritance. Kantarci et al. (2008) reported a 9-year-old boy with classic features of the disorder due to a homozygous truncating mutation in the LRP2 gene resulting from paternal uniparental isodisomy for chromosome 2. The unaffected mother did not carry the mutation. The boy did not have expanded features, suggesting | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. ) and vitamin D-binding proteins (see DBP, 139200).
Inheritance
Donnai-Barrow syndrome usually shows an autosomal recessive mode of inheritance. Kantarci et al. (2008) reported a 9-year-old boy with classic features of the disorder due to a homozygous truncating mutation in the LRP2 gene resulting from paternal uniparental isodisomy for chromosome 2. The unaffected mother did not carry the mutation. The boy did not have expanded features, suggesting that paternal chromosome 2 is unlikely to carry imprinted genes affecting growth or development. Kantarci et al. (2008) noted the implications for genetic counseling in this family.
Mapping
By linkage analysis of several families with Donnai-Barrow syndrome, Kantarci et al. (2007) identified an 18-Mb candidate region on chromosome 2q23.3-q31.1 (maximum 2-point lod score of 4. | [
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] |
omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. . The boy did not have expanded features, suggesting that paternal chromosome 2 is unlikely to carry imprinted genes affecting growth or development. Kantarci et al. (2008) noted the implications for genetic counseling in this family.
Mapping
By linkage analysis of several families with Donnai-Barrow syndrome, Kantarci et al. (2007) identified an 18-Mb candidate region on chromosome 2q23.3-q31.1 (maximum 2-point lod score of 4.31 and multipoint lod score of 6.24 between D2S1767 and D2S142).
Molecular Genetics
In 4 affected sibs with Donnai-Barrow syndrome from the United Arab Emirates, Kantarci et al. (2007) identified a homozygous mutation in the LRP2 gene (600073.0001). Kantarci et al. (2007) also identified pathogenic mutations in the LRP2 gene in | [
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] |
omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. (maximum 2-point lod score of 4.31 and multipoint lod score of 6.24 between D2S1767 and D2S142).
Molecular Genetics
In 4 affected sibs with Donnai-Barrow syndrome from the United Arab Emirates, Kantarci et al. (2007) identified a homozygous mutation in the LRP2 gene (600073.0001). Kantarci et al. (2007) also identified pathogenic mutations in the LRP2 gene in affected individuals reported by Donnai and Barrow (1993) (600073.0004-600073.0006) and Chassaing et al. (2003) (see, e.g., 600073.0002-600073.0003). Kantarci et al. (2007) identified mutations in the LRP2 gene (600073.0007; 600073.0008) in a Belgian child | [
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] |
omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. also identified pathogenic mutations in the LRP2 gene in affected individuals reported by Donnai and Barrow (1993) (600073.0004-600073.0006) and Chassaing et al. (2003) (see, e.g., 600073.0002-600073.0003). Kantarci et al. (2007) identified mutations in the LRP2 gene (600073.0007; 600073.0008) in a Belgian child reported by Devriendt et al. (1998) as having faciooculoacousticorenal syndrome. The findings confirmed that FOAR and Donnai-Barrow syndrome are the same entity.
INHERITANCE
- Autosomal recessive
GROWTH
Weight
- Birth weight - 50-97th percentile
HEAD & NECK
Head
- Large anterior fontanel
- Macrocephaly
Face
- Midface hypoplasia
Ears
- Deafness, sensorineural
- Low-set ears
- Posteriorly rotated | [
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] |
omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. 73.0008) in a Belgian child reported by Devriendt et al. (1998) as having faciooculoacousticorenal syndrome. The findings confirmed that FOAR and Donnai-Barrow syndrome are the same entity.
INHERITANCE
- Autosomal recessive
GROWTH
Weight
- Birth weight - 50-97th percentile
HEAD & NECK
Head
- Large anterior fontanel
- Macrocephaly
Face
- Midface hypoplasia
Ears
- Deafness, sensorineural
- Low-set ears
- Posteriorly rotated ears
Eyes
- Hypertelorism
- High myopia
- Loss of vision
- Iris coloboma
- Iris hypoplasia
- Cataract
- Enlarged globes
- Downslanting palpebral fissures
- Underorbital skin creases
- Retinal detachment
- Retinal dystrophy
- Prominent eyes
Nose
- Short nose
- Flat nasal bridge
- Broad tip
CARDIOVASCULAR
Heart
- Ventricular septal defect (less common)
- Double superior vena cava (rare)
RESPIRATORY
Lung
- Pulmonary hypoplasia secondary to | [
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omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. sensorineural
- Low-set ears
- Posteriorly rotated ears
Eyes
- Hypertelorism
- High myopia
- Loss of vision
- Iris coloboma
- Iris hypoplasia
- Cataract
- Enlarged globes
- Downslanting palpebral fissures
- Underorbital skin creases
- Retinal detachment
- Retinal dystrophy
- Prominent eyes
Nose
- Short nose
- Flat nasal bridge
- Broad tip
CARDIOVASCULAR
Heart
- Ventricular septal defect (less common)
- Double superior vena cava (rare)
RESPIRATORY
Lung
- Pulmonary hypoplasia secondary to diaphragmatic hernia
CHEST
Diaphragm
- Diaphragmatic hernia
- Diaphragmatic eventration
ABDOMEN
External Features
- Omphalocele
- Umbilical hernia
Gastrointestinal
- Intestinal malrotation
GENITOURINARY
Internal Genitalia (Female)
- Bicornuate uterus (rare)
SKELETAL
Skull
- Widened metopic suture
SKIN, NAILS, & HAIR
Skin
- Underorbital skin creases
NEUROLOGIC
Central Nervous System
- Partial or complete agenesis of corpus callosum
- Developmental delay
LABORATORY ABNORMALITIES
- Proteinuria
- Urinary excretion of retinol-binding proteins | [
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] |
omim | https://www.omim.org/entry/222448 | gGN9NP8 | DONNAI-BARROW SYNDROME | C1857277 | 25 | donnai-barrow syndrome. (rare)
RESPIRATORY
Lung
- Pulmonary hypoplasia secondary to diaphragmatic hernia
CHEST
Diaphragm
- Diaphragmatic hernia
- Diaphragmatic eventration
ABDOMEN
External Features
- Omphalocele
- Umbilical hernia
Gastrointestinal
- Intestinal malrotation
GENITOURINARY
Internal Genitalia (Female)
- Bicornuate uterus (rare)
SKELETAL
Skull
- Widened metopic suture
SKIN, NAILS, & HAIR
Skin
- Underorbital skin creases
NEUROLOGIC
Central Nervous System
- Partial or complete agenesis of corpus callosum
- Developmental delay
LABORATORY ABNORMALITIES
- Proteinuria
- Urinary excretion of retinol-binding proteins (RBP) and vitamin D-binding proteins (DBP)
MOLECULAR BASIS
- Caused by mutation in the low density lipoprotein receptor-related protein 2 gene (LRP2,
600073.0001
)
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. Description
Microphthalmia designates a heterogeneous group of ocular malformations with a more or less evident reduction in the size of the eyeball. Additional features include high hypermetropia and a short axial length. The size of the anterior chamber and the cornea may also be reduced, whereas the lens is normal or thicker than usual for age (summary by Fuchs et al., 2005). Genetic Heterogeneity of Isolated Microphthalmia
MCOP1 has been mapped to chromosome 14q32. MCOP2 (610093) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOP3 (611038) is caused by mutation in the RAX gene (601881) on chromosome 18q21.3. MCOP4 (613094) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22.1. MCOP5 ( | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. has been mapped to chromosome 14q32. MCOP2 (610093) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOP3 (611038) is caused by mutation in the RAX gene (601881) on chromosome 18q21.3. MCOP4 (613094) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22.1. MCOP5 (611040) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. MCOP6 (613517) is caused by mutation in the PRSS56 gene (613858) on chromosome 2q37.1. MCOP7 (613704) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOP8 (61 | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. 8q22.1. MCOP5 (611040) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. MCOP6 (613517) is caused by mutation in the PRSS56 gene (613858) on chromosome 2q37.1. MCOP7 (613704) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOP8 (615113) is caused by mutation in the ALDH1A3 gene (600463) on chromosome 15q26.
Nomenclature
The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. 12p13.1. MCOP8 (615113) is caused by mutation in the ALDH1A3 gene (600463) on chromosome 15q26.
Nomenclature
The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is rarely compatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'
Clinical Features
Cecchetto (1920) reported a pedigree in which 2 brothers, each | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'
Clinical Features
Cecchetto (1920) reported a pedigree in which 2 brothers, each married to a first cousin, had a child with bilateral clinical anophthalmia. The common grandparents were also first cousins. Hesselberg (1951) reported affected children from first-cousin parents. Sorsby (1934) discovered early reports of affected sibs with normal parents. Ashley (1947) reported an affected Japanese brother and sister. Warburg (1993) gave a comprehensive phenotypic and | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. reported a pedigree in which 2 brothers, each married to a first cousin, had a child with bilateral clinical anophthalmia. The common grandparents were also first cousins. Hesselberg (1951) reported affected children from first-cousin parents. Sorsby (1934) discovered early reports of affected sibs with normal parents. Ashley (1947) reported an affected Japanese brother and sister. Warburg (1993) gave a comprehensive phenotypic and etiologic classification of microphthalmos and ocular coloboma. She included the description of a consanguineous Arab family showing that the phenotype in autosomal recessive microphthalmos may include congenital cystic eye, anophthalmos, microphthalmos, or coloboma. Some affected family members were mentally retarded, while others were mentally healthy. Gill and Harris (1959) reported a family in which the proband and her great | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. Warburg (1993) gave a comprehensive phenotypic and etiologic classification of microphthalmos and ocular coloboma. She included the description of a consanguineous Arab family showing that the phenotype in autosomal recessive microphthalmos may include congenital cystic eye, anophthalmos, microphthalmos, or coloboma. Some affected family members were mentally retarded, while others were mentally healthy. Gill and Harris (1959) reported a family in which the proband and her great-aunt had microphthalmos. Wolff (1930) described a family of 10 children whose parents were first cousins and among whom 3 males and 2 females had microphthalmos, high-grade hyperopia (up to +20d), and glaucoma. Holst (1952) observed 6 cases in 2 related sibships. Oliveira da Silva and Santana de Sousa (1981) | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. reported a family in which the proband and her great-aunt had microphthalmos. Wolff (1930) described a family of 10 children whose parents were first cousins and among whom 3 males and 2 females had microphthalmos, high-grade hyperopia (up to +20d), and glaucoma. Holst (1952) observed 6 cases in 2 related sibships. Oliveira da Silva and Santana de Sousa (1981) used the term 'clinical anophthalmia' for this condition, to signify that clinically the eye appears to be absent, whereas in fact it is only very small. They described an instructive inbred kindred with 4 affected individuals in 3 separate sibships. Bessant et al. (1999) reported the phenotypic findings in affected individuals in a Pakistani family in which microphthalmia showed linkage to 14q32 (Bessant | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. va and Santana de Sousa (1981) used the term 'clinical anophthalmia' for this condition, to signify that clinically the eye appears to be absent, whereas in fact it is only very small. They described an instructive inbred kindred with 4 affected individuals in 3 separate sibships. Bessant et al. (1999) reported the phenotypic findings in affected individuals in a Pakistani family in which microphthalmia showed linkage to 14q32 (Bessant et al., 1998). All affected individuals had bilateral microphthalmia associated with anterior segment abnormalities, and the best visual acuity achieved was 'perception of light.' Corneal changes included partial or complete congenital sclerocornea (see 181700 and 269400), and the later development of corneal vascularization and anterior staphyloma. Intraocular pressure was greatly elevated in many cases. Sclerocornea has been observed in association with microphthalmia as | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. showed linkage to 14q32 (Bessant et al., 1998). All affected individuals had bilateral microphthalmia associated with anterior segment abnormalities, and the best visual acuity achieved was 'perception of light.' Corneal changes included partial or complete congenital sclerocornea (see 181700 and 269400), and the later development of corneal vascularization and anterior staphyloma. Intraocular pressure was greatly elevated in many cases. Sclerocornea has been observed in association with microphthalmia as part of the MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome (309801).
Mapping
In a consanguineous 5-generation Pakistani family in which 6 living members were affected by isolated congenital microphthalmia, Bessant et al. (1998) used whole-genome linkage analysis to map the gene to 14q32. Linkage analysis gave a maximum 2-point lod score of 3 | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. been observed in association with microphthalmia as part of the MIDAS (microphthalmia, dermal aplasia, and sclerocornea) syndrome (309801).
Mapping
In a consanguineous 5-generation Pakistani family in which 6 living members were affected by isolated congenital microphthalmia, Bessant et al. (1998) used whole-genome linkage analysis to map the gene to 14q32. Linkage analysis gave a maximum 2-point lod score of 3.55 for the marker D14S65. Surrounding this marker was a region of homozygosity of 7.3 cM, between markers D14S987 and D14S267, within which the disease gene was predicted to lie. The genes for several eye-specific transcription factors are located on 14q and in the syntenic region of mouse chromosome 12.
Animal Model
Breitman et al. (1987) created microphthalmia in | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. gave a maximum 2-point lod score of 3.55 for the marker D14S65. Surrounding this marker was a region of homozygosity of 7.3 cM, between markers D14S987 and D14S267, within which the disease gene was predicted to lie. The genes for several eye-specific transcription factors are located on 14q and in the syntenic region of mouse chromosome 12.
Animal Model
Breitman et al. (1987) created microphthalmia in transgenic mice by targeting expression of the diphtheria toxin gene. They used the mouse gamma-2-crystallin promoter fused to a gene encoding a site of toxic gene product to target expression of the diphtheria toxin gene to the mouse eye lens. As little as one molecule per cell of the toxin is estimated to be cytotoxic. The process was referred to as genetic ablation. Subsequent generations of mice showed microphthalmia without evidence of other abnormalities. Palmiter et al | [
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omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. . (1987) created microphthalmia in transgenic mice by targeting expression of the diphtheria toxin gene. They used the mouse gamma-2-crystallin promoter fused to a gene encoding a site of toxic gene product to target expression of the diphtheria toxin gene to the mouse eye lens. As little as one molecule per cell of the toxin is estimated to be cytotoxic. The process was referred to as genetic ablation. Subsequent generations of mice showed microphthalmia without evidence of other abnormalities. Palmiter et al. (1987) independently described a similar method to effect the ablation of cells within the exocrine pancreas. Used for the microinjection was a construct in which the elastase I (130120) promoter/enhancer was fused to a gene for diphtheria toxin A polypeptide. The recessive mouse mutation 'or(J),' which causes microphthalmia, progressive destruction of the retina, and absence of the optic nerve, is caused by mutation in the Chx10 gene | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. without evidence of other abnormalities. Palmiter et al. (1987) independently described a similar method to effect the ablation of cells within the exocrine pancreas. Used for the microinjection was a construct in which the elastase I (130120) promoter/enhancer was fused to a gene for diphtheria toxin A polypeptide. The recessive mouse mutation 'or(J),' which causes microphthalmia, progressive destruction of the retina, and absence of the optic nerve, is caused by mutation in the Chx10 gene; see 142993.
HEENT
- Microphthalmos
- Anophthalmos
- Nanophthalmos
- High-grade hyperopia
- Glaucoma
Inheritance
- Autosomal recessive
- also dominant forms
▲ Close | [
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] |
omim | https://www.omim.org/entry/251600 | J3qO9Jj | MICROPHTHALMIA, ISOLATED 1 | C1855052 | 26 | microphthalmia, isolated 1. , is caused by mutation in the Chx10 gene; see 142993.
HEENT
- Microphthalmos
- Anophthalmos
- Nanophthalmos
- High-grade hyperopia
- Glaucoma
Inheritance
- Autosomal recessive
- also dominant forms
▲ Close | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. Donnai–Barrow syndromeDonnai–Barrow syndrome is inherited in an autosomal recessive manner.SpecialtyMedical genetics
Donnai–Barrow syndrome is a genetic disorder first described by Dian Donnai and Margaret Barrow in 1993. It is associated with LRP2. It is an inherited (genetic) disorder that affects many parts of the body.
Contents
1 Presentation
2 Causes
2.1 Inherited mutation
3 Diagnosis
4 Management
5 Epidemiology
6 References
7 External links
Presentation
This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
Individuals with Donnai–Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsighted | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. Management
5 Epidemiology
6 References
7 External links
Presentation
This disorder is characterized by unusual facial features, including prominent, wide-set eyes with outer corners that point downward; a short bulbous nose with a flat nasal bridge; ears that are rotated backward; and a widow's peak hairline.
Individuals with Donnai–Barrow syndrome have severe hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). In addition, they often experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).
In almost all people with Donnai–Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. experience vision problems, including extreme nearsightedness (high myopia), detachment or deterioration of the light-sensitive tissue in the back of the eye (the retina), and progressive vision loss. Some have a gap or split in the colored part of the eye (iris coloboma).
In almost all people with Donnai–Barrow syndrome, the tissue connecting the left and right halves of the brain (corpus callosum) is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.
People with Donnai–Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. is underdeveloped or absent. Affected individuals may also have other structural abnormalities of the brain. They generally have mild to moderate intellectual disability and developmental delay.
People with Donnai–Barrow syndrome may also have a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia. This potentially serious birth defect allows the stomach and intestines to move into the chest and possibly crowd the developing heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai–Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.
Causes
Mutations in the LRP2 gene cause Donnai–Barrow syndrome. The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. Receptor proteins have | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. heart and lungs. An opening in the wall of the abdomen (an omphalocele) that allows the abdominal organs to protrude through the navel may also occur in affected individuals. Occasionally people with Donnai–Barrow syndrome have abnormalities of the intestine, heart, or other organs and scoliosis.
Causes
Mutations in the LRP2 gene cause Donnai–Barrow syndrome. The LRP2 gene provides instructions for making a protein called megalin, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. Megalin has many ligands involved in various body processes, including the absorption of vitamins A and D, immune functioning, stress response, and the transport of fats in the bloodstream.
Megalin is embedded in the membrane of cells that line the surfaces and cavities of the body (epithelial cells | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. , which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. Megalin has many ligands involved in various body processes, including the absorption of vitamins A and D, immune functioning, stress response, and the transport of fats in the bloodstream.
Megalin is embedded in the membrane of cells that line the surfaces and cavities of the body (epithelial cells). The receptor helps move its ligands from the cell surface into the cell (endocytosis). It is active in the development and function of many parts of the body, including the brain and spinal cord (central nervous system), eyes, ears, lungs, intestine, reproductive system, and the small tubes in the kidneys where urine is formed (renal tubules).
LRP2 gene mutations that cause Donnai–Barrow syndrome are believed to result | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. the surfaces and cavities of the body (epithelial cells). The receptor helps move its ligands from the cell surface into the cell (endocytosis). It is active in the development and function of many parts of the body, including the brain and spinal cord (central nervous system), eyes, ears, lungs, intestine, reproductive system, and the small tubes in the kidneys where urine is formed (renal tubules).
LRP2 gene mutations that cause Donnai–Barrow syndrome are believed to result in the absence of functional megalin protein. The lack of functional megalin in the renal tubules causes megalin's various ligands to be excreted in the urine rather than being absorbed back into the bloodstream. The features of Donnai–Barrow syndrome are probably caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of the nonfunctional megalin protein. However, it is unclear how these | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. nai–Barrow syndrome are believed to result in the absence of functional megalin protein. The lack of functional megalin in the renal tubules causes megalin's various ligands to be excreted in the urine rather than being absorbed back into the bloodstream. The features of Donnai–Barrow syndrome are probably caused by the inability of megalin to help absorb these ligands, disruption of biochemical signaling pathways, or other effects of the nonfunctional megalin protein. However, it is unclear how these abnormalities result in the specific signs and symptoms of the disorder.
A condition previously classified as a separate disorder called facio-oculo-acoustico-renal (FOAR) syndrome has also been found to be caused by LRP2 mutations. FOAR syndrome is now considered to be the same disorder as Donnai–Barrow syndrome.
Inherited mutation
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. alin protein. However, it is unclear how these abnormalities result in the specific signs and symptoms of the disorder.
A condition previously classified as a separate disorder called facio-oculo-acoustico-renal (FOAR) syndrome has also been found to be caused by LRP2 mutations. FOAR syndrome is now considered to be the same disorder as Donnai–Barrow syndrome.
Inherited mutation
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. In almost all cases, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms of the condition.
One individual with Donnai–Barrow syndrome was found to have inherited both copies of the mutated gene from his father as a result of a genetic change called uniparental disomy (UPD). UPD occurs when a person receives two copies of a | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. which means both copies of the gene in each cell have mutations. In almost all cases, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs and symptoms of the condition.
One individual with Donnai–Barrow syndrome was found to have inherited both copies of the mutated gene from his father as a result of a genetic change called uniparental disomy (UPD). UPD occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development.
Diagnosis
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Management
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Epidemiology
Donnai–Barrow syndrome appears to be | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. UPD occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development.
Diagnosis
This section is empty. You can help by adding to it. (December 2017)
Management
This section is empty. You can help by adding to it. (December 2017)
Epidemiology
Donnai–Barrow syndrome appears to be a rare disorder. A few dozen affected individuals have been reported in many regions of the world.
References
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. Donnai–Barrow syndrome appears to be a rare disorder. A few dozen affected individuals have been reported in many regions of the world.
References
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}Donnai, D | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}Donnai, D; Barrow, M (1993). "Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?". American Journal of Medical Genetics. 47 (5): 679–682. doi:10.1002/ajmg.1320470518. PMID 8266995.
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. weight:inherit}Donnai, D; Barrow, M (1993). "Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, and sensorineural deafness: a newly recognized autosomal recessive disorder?". American Journal of Medical Genetics. 47 (5): 679–682. doi:10.1002/ajmg.1320470518. PMID 8266995.
^ Kantarci S; Al-Gazali L; Hill RS; et al. (August 2007). "Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes". Nat. Genet. 39 (8): 957–9. doi:10.1038/ng2063. PMC 2891728. PMID 17632 | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. 5.
^ Kantarci S; Al-Gazali L; Hill RS; et al. (August 2007). "Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes". Nat. Genet. 39 (8): 957–9. doi:10.1038/ng2063. PMC 2891728. PMID 17632512.
^ a b c d e f g
"Donnai-Barrow syndrome" (online). Condition summary of this genetic disorder. U.S. National Library of Medicine of the National Institutes of Health. Reviewed May 2009. Retrieved 2010-12-19. Check date values in: |date= (help) This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. PMC 2891728. PMID 17632512.
^ a b c d e f g
"Donnai-Barrow syndrome" (online). Condition summary of this genetic disorder. U.S. National Library of Medicine of the National Institutes of Health. Reviewed May 2009. Retrieved 2010-12-19. Check date values in: |date= (help) This article incorporates text from the United States National Library of Medicine, which is in the public domain.
^ a b c d e f g The sources below were used to develop this article's condition summary on Donnai-Barrow syndrome.
Chassaing, N; Lacombe, D; Carles, D; Calvas, P; Saura, R; Bieth, E (2003). "Donnai-Barrow syndrome: four additional patients". American Journal of Medical Genetics Part A. 121A (3 | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. , which is in the public domain.
^ a b c d e f g The sources below were used to develop this article's condition summary on Donnai-Barrow syndrome.
Chassaing, N; Lacombe, D; Carles, D; Calvas, P; Saura, R; Bieth, E (2003). "Donnai-Barrow syndrome: four additional patients". American Journal of Medical Genetics Part A. 121A (3): 258–62. doi:10.1002/ajmg.a.20266. PMID 12923867.
Chen, CP (2007). "Syndromes and disorders associated with omphalocele (III): single gene disorders, neural tube defects, diaphragmatic defects and others". Taiwanese Journal of Obstetrics & Gynecology. 46 (2): 111–20. doi:10.1016/S1028 | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. of Medical Genetics Part A. 121A (3): 258–62. doi:10.1002/ajmg.a.20266. PMID 12923867.
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Kantarci, S; Donnai, D; Noonan, KM; Pober, BR; Pagon, RA; Bird, TC; Dolan, CR; Stephens, K (1993). "Donnai-Barrow Syndrome". PMID 20301732. Cite journal requires |journal= ( | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. doi:10.1016/S1028-4559(07)60004-7. PMID 17638618.
Kantarci, S; Donnai, D; Noonan, KM; Pober, BR; Pagon, RA; Bird, TC; Dolan, CR; Stephens, K (1993). "Donnai-Barrow Syndrome". PMID 20301732. Cite journal requires |journal= (help)
Kantarci, S; Al-Gazali, L; Hill, RS; Donnai, D; Black, GC; Bieth, E; Chassaing, N; Lacombe, D; Devriendt, K (2007). "Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustic | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. 2. Cite journal requires |journal= (help)
Kantarci, S; Al-Gazali, L; Hill, RS; Donnai, D; Black, GC; Bieth, E; Chassaing, N; Lacombe, D; Devriendt, K (2007). "Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes". Nature Genetics. 39 (8): 957–9. doi:10.1038/ng2063. PMC 2891728. PMID 17632512.
Kantarci, S; Ragge, NK; Thomas, NS; Robinson, DO; Noonan, KM; Russell, MK; Donnai, D; Raymond, FL; Walsh | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. Barrow and facio-oculo-acoustico-renal syndromes". Nature Genetics. 39 (8): 957–9. doi:10.1038/ng2063. PMC 2891728. PMID 17632512.
Kantarci, S; Ragge, NK; Thomas, NS; Robinson, DO; Noonan, KM; Russell, MK; Donnai, D; Raymond, FL; Walsh, CA (2008). "Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy". American Journal of Medical Genetics Part A. 146A (14): 1842–7. doi:10.1002/ajmg.a.32381. PMC 2891749. PMID 18553518.
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. D; Raymond, FL; Walsh, CA (2008). "Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy". American Journal of Medical Genetics Part A. 146A (14): 1842–7. doi:10.1002/ajmg.a.32381. PMC 2891749. PMID 18553518.
Patel, N; Hejkal, T; Katz, A; Margalit, E (2007). "Ocular manifestations of Donnai-Barrow syndrome". Journal of Child Neurology. 22 (4): 462–4. doi:10.1177/0883073807301933. PMID 17621530.
Pober, BR; Longoni, M; Noonan, KM ( | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. PMID 18553518.
Patel, N; Hejkal, T; Katz, A; Margalit, E (2007). "Ocular manifestations of Donnai-Barrow syndrome". Journal of Child Neurology. 22 (4): 462–4. doi:10.1177/0883073807301933. PMID 17621530.
Pober, BR; Longoni, M; Noonan, KM (2009). "A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome: clinical features and differential diagnosis". Birth Defects Research. Part A, Clinical and Molecular Teratology. 85 (1): 76–81. doi:10.1002/bdra.20534. PMC 2882234. PMID 19089858.
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. oni, M; Noonan, KM (2009). "A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome: clinical features and differential diagnosis". Birth Defects Research. Part A, Clinical and Molecular Teratology. 85 (1): 76–81. doi:10.1002/bdra.20534. PMC 2882234. PMID 19089858.
"Bulleted reference list (above)" (online). U.S. National Library of Medicine of the National Institutes of Health. Reviewed May 2009. Retrieved 2010-12-19. Check date values in: |date= (help)
This article incorporates text from the United States National Library of Medicine (NLM page URL), which is in the public domain.
External links
ClassificationDOMIM: 222448MeSH: C536390 | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. PMID 19089858.
"Bulleted reference list (above)" (online). U.S. National Library of Medicine of the National Institutes of Health. Reviewed May 2009. Retrieved 2010-12-19. Check date values in: |date= (help)
This article incorporates text from the United States National Library of Medicine (NLM page URL), which is in the public domain.
External links
ClassificationDOMIM: 222448MeSH: C536390 C536390, C536390External resourcesOrphanet: 2143
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. 222448MeSH: C536390 C536390, C536390External resourcesOrphanet: 2143
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. output .navbar-ct-mini{font-size:114%;margin:0 4em}.mw-parser-output .infobox .navbar{font-size:100%}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}vteCell surface receptor deficienciesG protein-coupled receptor(including hormone)Class A
TSHR (Congenital hypothyroidism 1)
LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
GnRHR (Gonadotropin-releasing hormone insensitivity)
EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. left;text-align:left;margin-right:0.5em}vteCell surface receptor deficienciesG protein-coupled receptor(including hormone)Class A
TSHR (Congenital hypothyroidism 1)
LHCGR (Luteinizing hormone insensitivity, Leydig cell hypoplasia, Male-limited precocious puberty)
FSHR (Follicle-stimulating hormone insensitivity, XX gonadal dysgenesis)
GnRHR (Gonadotropin-releasing hormone insensitivity)
EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
AVPR2 (Nephrogenic diabetes insipidus 1)
PTGER2 (Aspirin-induced asthma)
Class B
PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C
CASR (Familial hypocalciuric hypercalcemia)
Class F
FZD4 (Familial exudative vitreoretinopathy 1)
Enzyme-linked receptor(includinggrowth factor)RTK
ROR2 (Robinow syndrome)
FGFR1 (Pfei | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. ardenburg syndrome 4a, Hirschsprung's disease 2)
AVPR2 (Nephrogenic diabetes insipidus 1)
PTGER2 (Aspirin-induced asthma)
Class B
PTH1R (Jansen's metaphyseal chondrodysplasia)
Class C
CASR (Familial hypocalciuric hypercalcemia)
Class F
FZD4 (Familial exudative vitreoretinopathy 1)
Enzyme-linked receptor(includinggrowth factor)RTK
ROR2 (Robinow syndrome)
FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
INSR (Donohue syndrome
Rabson–Mendenhall syndrome)
NTRK1 (Congenital insensitivity to pain with anhi | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. Robinow syndrome)
FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
INSR (Donohue syndrome
Rabson–Mendenhall syndrome)
NTRK1 (Congenital insensitivity to pain with anhidrosis)
KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
STPK
AMHR2 (Persistent Müllerian duct syndrome II)
TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
GC
GUCY2D (Leber's congenital amaurosis 1)
JAK-STAT
Type I cytokine receptor: GH (Laron | [
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. NTRK1 (Congenital insensitivity to pain with anhidrosis)
KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
STPK
AMHR2 (Persistent Müllerian duct syndrome II)
TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
TGFBR1/TGFBR2 (Loeys–Dietz syndrome)
GC
GUCY2D (Leber's congenital amaurosis 1)
JAK-STAT
Type I cytokine receptor: GH (Laron syndrome)
CSF2RA (Surfactant metabolism dysfunction 4)
MPL (Congenital amegakaryocytic thrombocytopenia)
TNF receptor
TNFRSF1A (TNF receptor associated periodic syndrome)
TNFRSF13B (Selective immunoglobulin A deficiency 2)
TNFRSF5 (Hyper-IgM syndrome type 3)
TNFRSF13C (CVID4)
TNFRSF13B (CVID2)
TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
Lipid receptor
LRP: LRP2 ( | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. STAT
Type I cytokine receptor: GH (Laron syndrome)
CSF2RA (Surfactant metabolism dysfunction 4)
MPL (Congenital amegakaryocytic thrombocytopenia)
TNF receptor
TNFRSF1A (TNF receptor associated periodic syndrome)
TNFRSF13B (Selective immunoglobulin A deficiency 2)
TNFRSF5 (Hyper-IgM syndrome type 3)
TNFRSF13C (CVID4)
TNFRSF13B (CVID2)
TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
Lipid receptor
LRP: LRP2 (Donnai–Barrow syndrome)
LRP4 (Cenani–Lenz syndactylism)
LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
LDLR (LDLR Familial hypercholesterolemia)
Other/ungrouped
Immunoglobulin superfamily: AGM3, 6
Integrin: LAD1
Glanzmann's thrombasthenia
Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. syndrome 1A)
Lipid receptor
LRP: LRP2 (Donnai–Barrow syndrome)
LRP4 (Cenani–Lenz syndactylism)
LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
LDLR (LDLR Familial hypercholesterolemia)
Other/ungrouped
Immunoglobulin superfamily: AGM3, 6
Integrin: LAD1
Glanzmann's thrombasthenia
Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR hypohidrotic ectodermal dysplasia)
PTCH1 (Nevoid basal-cell carcinoma syndrome)
BMPR1A (BMPR1A juvenile polyposis syndrome)
IL2RG (X-linked severe combined immunodeficiency)
See also
cell surface receptors
<!--
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. AR (EDAR hypohidrotic ectodermal dysplasia)
PTCH1 (Nevoid basal-cell carcinoma syndrome)
BMPR1A (BMPR1A juvenile polyposis syndrome)
IL2RG (X-linked severe combined immunodeficiency)
See also
cell surface receptors
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. 327 1 Template:Reflist
28.01% 138.113 9 Template:Cite_journal
25.72% 126.822 2 Template:Infobox
21.80% 107.500 1 Template:Infobox_medical_condition_(new)
18.43% 90.844 4 Template:Cn
14.81% 73.001 4 Template:Fix
9.39% 46.312 1 Template:Medical_resources
8.88% 43.794 8 Template:Category_handler
6.23% 30.699 1 Template:Cell_surface_receptor_deficiencies
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wikipedia | https://en.wikipedia.org/wiki/Donnai%E2%80%93Barrow_syndrome | oxg1MMJ | Donnai–Barrow syndrome | C1857277 | 27 | donnai–barrow syndrome. .88% 43.794 8 Template:Category_handler
6.23% 30.699 1 Template:Cell_surface_receptor_deficiencies
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. SummaryClinical characteristics.Potocki-Lupski syndrome (PTLS) is characterized by cognitive, behavioral, and medical manifestations. Cognitively, most individuals present with developmental delay, later meeting criteria for moderate intellectual disability. Behaviorally, issues with attention, hyperactivity, withdrawal, and anxiety may be seen. Some individuals meet criteria for autism spectrum disorder. Medically, hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, hypoglycemia associated with growth hormone deficiency, and mildly dysmorphic facial features are observed. Medical manifestations typically lead to identification of PTLS in infancy; however, those with only behavioral and cognitive manifestations may be identified in later childhood.Diagnosis/testing.The diagnosis of PTLS is established by detection of a heterozygous duplication at chromosome 17p11.2 that encompasses RAI1. A recurrent 3.7-Mb duplication accounts for approximately two thirds of 17p11.2 duplications; approximately one third are non- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. hypoglycemia associated with growth hormone deficiency, and mildly dysmorphic facial features are observed. Medical manifestations typically lead to identification of PTLS in infancy; however, those with only behavioral and cognitive manifestations may be identified in later childhood.Diagnosis/testing.The diagnosis of PTLS is established by detection of a heterozygous duplication at chromosome 17p11.2 that encompasses RAI1. A recurrent 3.7-Mb duplication accounts for approximately two thirds of 17p11.2 duplications; approximately one third are non-recurrent duplications that encompass RAI1 and vary in size from 0.41 Mb to 19.7 Mb.Management.Treatment of manifestations: A multidisciplinary evaluation involving healthcare providers from multiple specialties varies by the age and presenting issues of each individual. Management of all manifestations of PTLS is per standard care.Surveillance: Routine monitoring for growth deceleration, short stature, failure to thrive; periodic developmental assessment by a developmental specialist; screen for behavior problems at every | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. 1.2 duplications; approximately one third are non-recurrent duplications that encompass RAI1 and vary in size from 0.41 Mb to 19.7 Mb.Management.Treatment of manifestations: A multidisciplinary evaluation involving healthcare providers from multiple specialties varies by the age and presenting issues of each individual. Management of all manifestations of PTLS is per standard care.Surveillance: Routine monitoring for growth deceleration, short stature, failure to thrive; periodic developmental assessment by a developmental specialist; screen for behavior problems at every visit; consultation with a psychiatrist and/or psychologist if there are behavioral concerns; follow up of congenital heart disease as per cardiac consultant.Genetic counseling.PTLS is inherited in an autosomal dominant manner. The majority of affected individuals have a de novo duplication; however, parent-to-child transmission has been reported. If the 17p11.2 duplication identified in the proband is not identified in either parent, the risk for | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. by a developmental specialist; screen for behavior problems at every visit; consultation with a psychiatrist and/or psychologist if there are behavioral concerns; follow up of congenital heart disease as per cardiac consultant.Genetic counseling.PTLS is inherited in an autosomal dominant manner. The majority of affected individuals have a de novo duplication; however, parent-to-child transmission has been reported. If the 17p11.2 duplication identified in the proband is not identified in either parent, the risk for future pregnancies could be slightly greater than that of the general population (though still <1%) because of the possibility of parental somatic and or germline mosaicism for the duplication. If one of the parents has the 17p11.2 duplication, the risk to each sib of inheriting the duplication is 50%. It is not possible to reliably predict the phenotype of individuals who inherit the duplication. Prenatal testing and preimplantation genetic testing using chromosomal | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. proband is not identified in either parent, the risk for future pregnancies could be slightly greater than that of the general population (though still <1%) because of the possibility of parental somatic and or germline mosaicism for the duplication. If one of the parents has the 17p11.2 duplication, the risk to each sib of inheriting the duplication is 50%. It is not possible to reliably predict the phenotype of individuals who inherit the duplication. Prenatal testing and preimplantation genetic testing using chromosomal microarray (CMA) to detect the 17q11.2 duplication found in the proband are possible.DiagnosisSuggestive FindingsPotocki-Lupski syndrome (PTLS) should be suspected in individuals with the following :Neurodevelopmental findings:Mild-to-moderate infantile hypotonia with oropharyngeal dysphagia and failure to thriveDevelopmental delay; intellectual disability (typically moderate)Communication disorder with verbal apraxia and abnormalities of intonation and pros | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. the duplication. Prenatal testing and preimplantation genetic testing using chromosomal microarray (CMA) to detect the 17q11.2 duplication found in the proband are possible.DiagnosisSuggestive FindingsPotocki-Lupski syndrome (PTLS) should be suspected in individuals with the following :Neurodevelopmental findings:Mild-to-moderate infantile hypotonia with oropharyngeal dysphagia and failure to thriveDevelopmental delay; intellectual disability (typically moderate)Communication disorder with verbal apraxia and abnormalities of intonation and prosodySleep-disordered breathing (most evident on sleep studies)Features of autism spectrum disorder; hyperactivityCongenital heart disease, typically left ventricular outflow track spectrum and/or rhythm disturbancesGrowth hormone deficiencyMildly to nonspecific dysmorphic facial features (see Figure 1).Figure 1. Individuals with Potocki-Lupski syndrome. The facial features are not strikingly dysmorphic though common findings include micrognathia (in early childhood | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. apraxia and abnormalities of intonation and prosodySleep-disordered breathing (most evident on sleep studies)Features of autism spectrum disorder; hyperactivityCongenital heart disease, typically left ventricular outflow track spectrum and/or rhythm disturbancesGrowth hormone deficiencyMildly to nonspecific dysmorphic facial features (see Figure 1).Figure 1. Individuals with Potocki-Lupski syndrome. The facial features are not strikingly dysmorphic though common findings include micrognathia (in early childhood) and downslanting palpebral fissures. A. Female age three years ten monthsEstablishing the DiagnosisThe diagnosis of PTLS is established by detection of a heterozygous duplication at chromosome 17p11.2 that encompasses RAI1 . Most individuals with PTLS are identified by chromosomal microarray performed in the context of evaluation for hypotonia, failure to thrive, developmental delay, intellectual disability, or autism spectrum disorder.For this | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. common findings include micrognathia (in early childhood) and downslanting palpebral fissures. A. Female age three years ten monthsEstablishing the DiagnosisThe diagnosis of PTLS is established by detection of a heterozygous duplication at chromosome 17p11.2 that encompasses RAI1 . Most individuals with PTLS are identified by chromosomal microarray performed in the context of evaluation for hypotonia, failure to thrive, developmental delay, intellectual disability, or autism spectrum disorder.For this GeneReview, the 17p11.2 recurrent duplication, observed in approximately two thirds of individuals with PTLS, is defined by a 3.7-Mb duplication at the proximal region of chromosome 17 spanning an approximate interval of 16,757,111-20,219,651 in the reference genome (NCBI Build hg19 genome.ucsc.edu/cgi-bin/hgGateway). Note: | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. , intellectual disability, or autism spectrum disorder.For this GeneReview, the 17p11.2 recurrent duplication, observed in approximately two thirds of individuals with PTLS, is defined by a 3.7-Mb duplication at the proximal region of chromosome 17 spanning an approximate interval of 16,757,111-20,219,651 in the reference genome (NCBI Build hg19 genome.ucsc.edu/cgi-bin/hgGateway). Note: Non-recurrent duplications (which encompass RAI1) account for approximately one third of individuals with PTLS and vary in size from 0.41 Mb to 19.7 Mb (see Molecular Pathogenesis).ISCN nomenclature for the recurrent duplication is: arr 17p11.2(16,757,111-20,219,651)x3. Note: Since this duplication is recurrent and mediated by segmental duplications, the unique genetic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. -bin/hgGateway). Note: Non-recurrent duplications (which encompass RAI1) account for approximately one third of individuals with PTLS and vary in size from 0.41 Mb to 19.7 Mb (see Molecular Pathogenesis).ISCN nomenclature for the recurrent duplication is: arr 17p11.2(16,757,111-20,219,651)x3. Note: Since this duplication is recurrent and mediated by segmental duplications, the unique genetic sequence that is duplicated is the same in all individuals with the syndrome; however, the reported size of the duplication may: (1) be slightly larger or smaller if adjacent segmental duplications are included in the size; and (2) vary based on the design of the microarray used to detect it (see Molecular Pathogenesis).Although several genes are within the 3.7-Mb recurrent duplication, only RAI1 has been implicated as the dosage-sensitive | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. is recurrent and mediated by segmental duplications, the unique genetic sequence that is duplicated is the same in all individuals with the syndrome; however, the reported size of the duplication may: (1) be slightly larger or smaller if adjacent segmental duplications are included in the size; and (2) vary based on the design of the microarray used to detect it (see Molecular Pathogenesis).Although several genes are within the 3.7-Mb recurrent duplication, only RAI1 has been implicated as the dosage-sensitive cause of the phenotype . (See Molecular Genetics for genes of interest in the duplicated region.)The best genomic testing method is chromosomal microarray (CMA) using oligonucleotide or SNP arrays that can detect the recurrent duplication in a proband. The ability to size the duplication depends on the type of microarray used and the density of probes in the 17p11.2 region. Note: (1) This duplication is the reciprocal recombination product of the Smith-Mage | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. only RAI1 has been implicated as the dosage-sensitive cause of the phenotype . (See Molecular Genetics for genes of interest in the duplicated region.)The best genomic testing method is chromosomal microarray (CMA) using oligonucleotide or SNP arrays that can detect the recurrent duplication in a proband. The ability to size the duplication depends on the type of microarray used and the density of probes in the 17p11.2 region. Note: (1) This duplication is the reciprocal recombination product of the Smith-Magenis syndrome (SMS) deletion; therefore, this region has been represented since the inception of array CGH technology. (2) Although interphase fluorescent in situ hybridization using RAI1 or high-resolution G-banded chromosome analysis can detect the recurrent 3.7-Mb duplication, these methods are highly dependent on cell preparation and technical skills, and thus lack sensitivity .Table 1. Genomic Testing Used in Potocki-Lupski SyndromeView in | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. duplication is the reciprocal recombination product of the Smith-Magenis syndrome (SMS) deletion; therefore, this region has been represented since the inception of array CGH technology. (2) Although interphase fluorescent in situ hybridization using RAI1 or high-resolution G-banded chromosome analysis can detect the recurrent 3.7-Mb duplication, these methods are highly dependent on cell preparation and technical skills, and thus lack sensitivity .Table 1. Genomic Testing Used in Potocki-Lupski SyndromeView in own windowDuplication 1MethodTest SensitivityProbandAt-Risk Family MembersHeterozygous duplication at 17p11.2 2:arr 17p11.2(16,757,111-20,219,651)x3 3CMA 4100%100%Targetedduplicationanalysis 5Notapplicable 6100%1. See Molecular Genetics for details of the duplication and genes of interest in the region. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. in Potocki-Lupski SyndromeView in own windowDuplication 1MethodTest SensitivityProbandAt-Risk Family MembersHeterozygous duplication at 17p11.2 2:arr 17p11.2(16,757,111-20,219,651)x3 3CMA 4100%100%Targetedduplicationanalysis 5Notapplicable 6100%1. See Molecular Genetics for details of the duplication and genes of interest in the region.2. For this GeneReview, the 17p11.2 recurrent duplication, observed in approximately two thirds of individuals with PTLS, is defined a 3.7-Mb duplication at the proximal region of chromosome 17 spanning an approximate interval of 16,757,111-20,219,651 in the reference genome. Non-recurrent duplications, which encompass RAI1, account for approximately one third of individuals with PTLS and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. of the duplication and genes of interest in the region.2. For this GeneReview, the 17p11.2 recurrent duplication, observed in approximately two thirds of individuals with PTLS, is defined a 3.7-Mb duplication at the proximal region of chromosome 17 spanning an approximate interval of 16,757,111-20,219,651 in the reference genome. Non-recurrent duplications, which encompass RAI1, account for approximately one third of individuals with PTLS and vary in size from 0.41 Mb to 19.7 Mb.3. Standardized ISCN annotation and interpretation for genomic variants from the Clinical Genome Resource Project (formerly the International Standards for Cytogenomic Arrays Consortium). Genomic coordinates represent the minimum duplication size associated with the 17p11.2 recurrent duplication as designated by ClinGen. Duplication coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the duplication | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. account for approximately one third of individuals with PTLS and vary in size from 0.41 Mb to 19.7 Mb.3. Standardized ISCN annotation and interpretation for genomic variants from the Clinical Genome Resource Project (formerly the International Standards for Cytogenomic Arrays Consortium). Genomic coordinates represent the minimum duplication size associated with the 17p11.2 recurrent duplication as designated by ClinGen. Duplication coordinates may vary slightly based on array design used by the testing laboratory. Note that the size of the duplication as calculated from these genomic positions may differ from the expected duplication size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller duplications within this region may be clinically distinct from Potocki-Lupski syndrome (see Genetically Related Disorders).4. Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 17p11.2 region.5. Targeted duplication analysis | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. the testing laboratory. Note that the size of the duplication as calculated from these genomic positions may differ from the expected duplication size due to the presence of segmental duplications near breakpoints. The phenotype of significantly larger or smaller duplications within this region may be clinically distinct from Potocki-Lupski syndrome (see Genetically Related Disorders).4. Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays. CMA designs in current clinical use target the 17p11.2 region.5. Targeted duplication analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods.6. Targeted duplication analysis is not appropriate for an individual in whom the 17p11.2 recurrent duplication was not detected by CMA designed to target this region.Clinical CharacteristicsClinical DescriptionPotocki-Lupski syndrome (PTLS) is characterized by developmental delay, intellectual disability, behavioral | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. p11.2 region.5. Targeted duplication analysis methods can include FISH, quantitative PCR (qPCR), and multiplex ligation-dependent probe amplification (MLPA) as well as other targeted quantitative methods.6. Targeted duplication analysis is not appropriate for an individual in whom the 17p11.2 recurrent duplication was not detected by CMA designed to target this region.Clinical CharacteristicsClinical DescriptionPotocki-Lupski syndrome (PTLS) is characterized by developmental delay, intellectual disability, behavioral disturbances, organ system involvement, and mildly dysmorphic facial features . See Figure 1.PTLS can manifest in infancy with hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, and hypoglycemia associated with growth hormone deficiency. In contrast, individuals who are more mildly affected may manifest cognitive and behavioral abnormalities only, and not be diagnosed until later in childhood .NeurodevelopmentalMild-to-moderate infantile hypotonia with oropharyngeal dysphagia is common | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. ) is characterized by developmental delay, intellectual disability, behavioral disturbances, organ system involvement, and mildly dysmorphic facial features . See Figure 1.PTLS can manifest in infancy with hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, and hypoglycemia associated with growth hormone deficiency. In contrast, individuals who are more mildly affected may manifest cognitive and behavioral abnormalities only, and not be diagnosed until later in childhood .NeurodevelopmentalMild-to-moderate infantile hypotonia with oropharyngeal dysphagia is common and contributes to poor feeding and mild-to-moderate gross motor delays . Poor feeding or poor weight gain can be an initial presentation. Infants and children have significantly lower weight for age, weight for length, and BMI for age than the reference population .Although gross motor delay is observed in the vast majority, most will achieve independent walking by age two years. Rarely, independent ambulation can be delayed until age four years.Cognitive impairment is one of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. to-moderate infantile hypotonia with oropharyngeal dysphagia is common and contributes to poor feeding and mild-to-moderate gross motor delays . Poor feeding or poor weight gain can be an initial presentation. Infants and children have significantly lower weight for age, weight for length, and BMI for age than the reference population .Although gross motor delay is observed in the vast majority, most will achieve independent walking by age two years. Rarely, independent ambulation can be delayed until age four years.Cognitive impairment is one of the most common characteristics of PTLS . The vast majority of individuals tested have moderate intellectual disability .Speech delay is universal. Standardized testing has revealed expressive and receptive language impairment which can include articulation difficulties and disordered intonation and prosody . Some individuals may exhibit verbal apraxia.While there are no formal studies of articulation and language abilities in teens and adults with PTLS, verbal abilities appear to improve both with age and speech therapy. Little data | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. until age four years.Cognitive impairment is one of the most common characteristics of PTLS . The vast majority of individuals tested have moderate intellectual disability .Speech delay is universal. Standardized testing has revealed expressive and receptive language impairment which can include articulation difficulties and disordered intonation and prosody . Some individuals may exhibit verbal apraxia.While there are no formal studies of articulation and language abilities in teens and adults with PTLS, verbal abilities appear to improve both with age and speech therapy. Little data regarding findings in adults are available; however, adults with a confirmed molecular genetic diagnosis who have been clinically evaluated have cognitive challenges.Sleep-disordered breathing. Although sleep disturbances are not often clinically recognized and significant airway obstruction is not found on examination, abnormalities frequently evident on sleep studies include sleep-disordered breathing such as mild central and/or obstructive sleep apnea . Children with sleep apnea may present with snoring or hyperactivity. In addition, periodic limb movement disorder is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. to improve both with age and speech therapy. Little data regarding findings in adults are available; however, adults with a confirmed molecular genetic diagnosis who have been clinically evaluated have cognitive challenges.Sleep-disordered breathing. Although sleep disturbances are not often clinically recognized and significant airway obstruction is not found on examination, abnormalities frequently evident on sleep studies include sleep-disordered breathing such as mild central and/or obstructive sleep apnea . Children with sleep apnea may present with snoring or hyperactivity. In addition, periodic limb movement disorder is commonly observed.Behavioral difficulties identified by objective measures and by parental reports include attention problems, withdrawal, and high levels of hyperactivity and anxiety. Reported deficits in executive functioning include initiating and shifting activities and working memory.Autism spectrum disorder (ASD) and/or autistic features (decreased eye contact, motor mannerisms or posturing, sensory hypersensitivity or preoccupation, repetitive behaviors, difficulty with transitions, lack of appropriate functional or symbolic play, and lack of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. or hyperactivity. In addition, periodic limb movement disorder is commonly observed.Behavioral difficulties identified by objective measures and by parental reports include attention problems, withdrawal, and high levels of hyperactivity and anxiety. Reported deficits in executive functioning include initiating and shifting activities and working memory.Autism spectrum disorder (ASD) and/or autistic features (decreased eye contact, motor mannerisms or posturing, sensory hypersensitivity or preoccupation, repetitive behaviors, difficulty with transitions, lack of appropriate functional or symbolic play, and lack of joint attention) are seen in affected individuals . Using validated scoring systems (ADI-R and ADOS-G), Treadwell-Deering et al found that approximately 60% of a small cohort of children with PTLS met criteria for ASD.Congenital Heart DiseaseCardiovascular anomalies are reported in about 40% of individuals with PTLS . The anomalies can include atrial septal defect and ventricular septal defect, as well as anomalies within the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK447920/ | ZkPkjMl | Potocki-Lupski Syndrome | C2931246 | 28 | potocki-lupski syndrome. lack of appropriate functional or symbolic play, and lack of joint attention) are seen in affected individuals . Using validated scoring systems (ADI-R and ADOS-G), Treadwell-Deering et al found that approximately 60% of a small cohort of children with PTLS met criteria for ASD.Congenital Heart DiseaseCardiovascular anomalies are reported in about 40% of individuals with PTLS . The anomalies can include atrial septal defect and ventricular septal defect, as well as anomalies within the left ventricular outflow track spectrum including bicuspid aortic valve, dilated aortic root, and hypoplastic left heart .A smaller percentage of individuals with PTLS have rhythm disturbances detected on ECG .Growth Hormone DeficiencyFive of seven individuals in the original description of PTLS had short stature; one of the five had documented growth hormone deficiency . In a second study, one of ten individuals had short stature (but not growth hormone deficiency) . Subsequently, additional individuals with | [
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