Entry - #618644 - OSTEOGENESIS IMPERFECTA, TYPE XX; OI20 - OMIM
# 618644

OSTEOGENESIS IMPERFECTA, TYPE XX; OI20


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q25.1 Osteogenesis imperfecta, type XX 618644 AR 3 MESD 607783
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
GROWTH
Height
- Short stature
Other
- Intrauterine growth retardation
HEAD & NECK
Head
- Microcephaly
- Relative macrocephaly (in 1 patient)
- Plagiocephaly
- Brachycephaly
- Sparse hair
Face
- Midface hypoplasia
- Retrognathia
- Prognathism, progressive
- Pointed chin
Ears
- Low-set ears
- Posteriorly rotated ears
- Crumpled ears
- Prominent ears
Eyes
- Arched eyebrows
- Sparse lateral eyebrows
- Prominent eyes
- Blue sclerae (in some patients, diminishes with age)
Nose
- Small nose
- Bulbous tip
Mouth
- Tented upper lip
- High-arched palate
- Narrow palate
Teeth
- Disorganized dentition
- Missing teeth
CHEST
External Features
- Narrow thorax
- Asymmetric thorax
Ribs Sternum Clavicles & Scapulae
- Multiple rib fractures (at birth and postnatally)
- Fractured clavicle
ABDOMEN
Gastrointestinal
- Feeding difficulties (in some patients)
GENITOURINARY
Internal Genitalia (Male)
- Cryptorchidism (in some patients)
SKELETAL
- Generalized osteopenia
- Multiple fractures (at birth and postnatally)
Skull
- Microcephaly
- Plagiocephaly
- Brachycephaly
- Soft calvarial bones
- Wormian bones
Spine
- Vertebral compression fractures
- Kyphoscoliosis, progressive
Limbs
- Rhizomelia
- Bowing of limbs
- Limited knee extension
Hands
- Long fingers
- Contractures of 2nd and 3rd fingers, bilateral
- Adducted thumbs
Feet
- Overlapping toes
NEUROLOGIC
Central Nervous System
- Delayed gross motor function
- Global developmental delay (in 1 patient)
- Speech delay (in 1 patient)
MISCELLANEOUS
- Shortened and bowed long bones may be observed on prenatal ultrasound
- Death due to respiratory failure has occurred in some patients
MOLECULAR BASIS
- Caused by mutation in the mesoderm development LRP chaperone gene (MESD, 607783.0001)
Osteogenesis imperfecta - PS166200 - 26 Entries
Location Phenotype Inheritance Phenotype
mapping key
Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
1p34.2 Osteogenesis imperfecta, type VIII AR 3 610915 P3H1 610339
3p22.3 Osteogenesis imperfecta, type VII AR 3 610682 CRTAP 605497
5q33.1 Osteogenesis imperfecta, type XVII AR 3 616507 SPARC 182120
6q14.1 Osteogenesis imperfecta, type XVIII AR 3 617952 TENT5A 611357
7p22.1 Osteogenesis imperfecta, type XXI AR 3 619131 KDELR2 609024
7q21.3 Osteogenesis imperfecta, type IV AD 3 166220 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type II AD 3 166210 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type III AD 3 259420 COL1A2 120160
8p21.3 Osteogenesis imperfecta, type XIII AR 3 614856 BMP1 112264
9q31.2 Osteogenesis imperfecta, type XIV AR 3 615066 TMEM38B 611236
11p15.5 Osteogenesis imperfecta, type V AD 3 610967 IFITM5 614757
11p11.2 Osteogenesis imperfecta, type XVI AR 3 616229 CREB3L1 616215
11q13.5 Osteogenesis imperfecta, type X AR 3 613848 SERPINH1 600943
11q23.3 Osteogenesis imperfecta, type XXIII AR 3 620639 PHLDB1 612834
12q13.12 Osteogenesis imperfecta, type XV AR 3 615220 WNT1 164820
12q13.13 Osteogenesis imperfecta, type XII AR 3 613849 SP7 606633
15q22.31 Osteogenesis imperfecta, type IX AR 3 259440 PPIB 123841
15q25.1 Osteogenesis imperfecta, type XX AR 3 618644 MESD 607783
17p13.3 Osteogenesis imperfecta, type VI AR 3 613982 SERPINF1 172860
17q21.2 Osteogenesis imperfecta, type XI AR 3 610968 FKBP10 607063
17q21.33 Osteogenesis imperfecta, type II AD 3 166210 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type IV AD 3 166220 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type I AD 3 166200 COL1A1 120150
17q21.33 Osteogenesis imperfecta, type III AD 3 259420 COL1A1 120150
22q13.2 Osteogenesis imperfecta, type XXII AR 3 619795 CCDC134 618788
Xp22.12 Osteogenesis imperfecta, type XIX XLR 3 301014 MBTPS2 300294

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type XX (OI20) is caused by homozygous or compound heterozygous mutation in the MESD gene (607783) on chromosome 15q25.


Description

Osteogenesis imperfecta type XX (OI20) is a progressive deforming bone disorder characterized by osteopenia, skeletal deformity, and both healed and new fractures on radiography. Several patients have died due to respiratory failure (Moosa et al., 2019).


Clinical Features

Moosa et al. (2019) reported 5 probands from consanguineous families who were clinically diagnosed with a progressive deforming type of osteogenesis imperfecta. Fractures were observed prenatally in 2 patients, and all had a fracture within the first 2 years of life. Treatment with bisphosphonates, undertaken in 4 of the patients, was unsuccessful. Three patients died of respiratory failure, 2 before 18 months of age and 1 at age 17 years. The oldest affected individuals, when assessed at ages 10 years and 16 years, respectively, were nonambulatory. Bluish sclerae were noted in the youngest individuals, but not in the older ones. None had dentinogenesis imperfecta, but the 3 older individuals had disorganized dentition and/or oligodontia. Global developmental delay or evidence of intellectual disability was present in 3 individuals.

Sturznickel et al. (2021) reported 3 stillborn sibs, born to nonconsanguineous parents of German origin, with osteogenesis imperfecta type XX. Gestational age of the stillbirths was 26, 22, and 14 weeks. All 3 stillbirths occurred after prenatal diagnosis of a skeletal disorder was made during the second trimester. Findings included a triangular face, blue sclerae, retrognathia, micromelia, angulated long bones, and bilateral clubfeet. The thorax was narrow, resulting in severe lung hypoplasia and congestion of the venous inflow tract of the heart, with consequent hepatomegaly and fetal hydrops. Multiple rib fractures and overtubulation of the long bones were seen on fetal autopsy. One of the stillbirths had a double kidney. Histologic evaluation showed impaired osseous development with altered osteocyte morphology and reduced canalicular connectivity. Examination of bone mineral density distribution showed an impaired and more heterogeneous matrix mineralization in the patients.


Inheritance

The transmission pattern of OI20 in the families reported by Moosa et al. (2019) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 5 probands with a progressive deforming type of osteogenesis imperfecta, who were negative for mutation in known OI-associated genes, Moosa et al. (2019) performed whole-exome sequencing and identified homozygosity for mutations in the MESD gene (607783.0001-607783.0004). The unaffected parents were heterozygous for the mutations, which were not common polymorphisms in public variant databases.

In 3 stillborn sibs with OI20, who were born to nonconsanguineous parents of German origin, Sturznickel et al. (2021) identified compound heterozygous mutations in the MESD gene, the previously identified 5-bp deletion (c.607_611del; 607783.0004) and a novel 1-bp deletion (c.265del; 607783.0005). Each parent was heterozygous for one of the disease-causing variants. Sequencing of the mRNA from the parents revealed a complete loss of the mRNA harboring the c.265del mutation, whereas the mRNA with the c.607_611del mutation was readily detected. The authors suggested that the prenatally lethal phenotype in this family was likely related to complete functional loss of one MESD allele, which could not be compensated by the residual function of the second allele.


REFERENCES

  1. Moosa, S., Yamamoto, G. L., Garbes, L., Keupp, K., Beleza-Meireles, A., Moreno, C. A., Valadares, E. R., de Sousa, S. B., Maia, S., Saraiva, J., Honjo, R. S., Kim, C.-A., and 21 others. Autosomal-recessive mutations in MESD cause osteogenesis imperfecta. Am. J. Hum. Genet. 105: 836-843, 2019. [PubMed: 31564437, images, related citations] [Full Text]

  2. Sturznickel, J., Jahn-Rickert, K., Zustin, J., Hennig, F., Delsmann, M. M., Schoner, K., Rehder, H., Kreczy, A., Schinke, T., Amling, M., Kornak, U., Oheim, R. Compound heterozygous frameshift mutations in MESD cause a lethal syndrome suggestive of osteogenesis imperfecta type XX. J. Bone Miner. Res. 36: 1077-1087, 2021. [PubMed: 33596325, related citations] [Full Text]


Contributors:
Sonja A. Rasmussen - updated : 01/31/2023
Creation Date:
Marla J. F. O'Neill : 10/25/2019
alopez : 04/17/2024
carol : 02/29/2024
carol : 01/31/2023
carol : 01/22/2020
carol : 10/28/2019
alopez : 10/25/2019

# 618644

OSTEOGENESIS IMPERFECTA, TYPE XX; OI20


DO: 0111849;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q25.1 Osteogenesis imperfecta, type XX 618644 Autosomal recessive 3 MESD 607783

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type XX (OI20) is caused by homozygous or compound heterozygous mutation in the MESD gene (607783) on chromosome 15q25.


Description

Osteogenesis imperfecta type XX (OI20) is a progressive deforming bone disorder characterized by osteopenia, skeletal deformity, and both healed and new fractures on radiography. Several patients have died due to respiratory failure (Moosa et al., 2019).


Clinical Features

Moosa et al. (2019) reported 5 probands from consanguineous families who were clinically diagnosed with a progressive deforming type of osteogenesis imperfecta. Fractures were observed prenatally in 2 patients, and all had a fracture within the first 2 years of life. Treatment with bisphosphonates, undertaken in 4 of the patients, was unsuccessful. Three patients died of respiratory failure, 2 before 18 months of age and 1 at age 17 years. The oldest affected individuals, when assessed at ages 10 years and 16 years, respectively, were nonambulatory. Bluish sclerae were noted in the youngest individuals, but not in the older ones. None had dentinogenesis imperfecta, but the 3 older individuals had disorganized dentition and/or oligodontia. Global developmental delay or evidence of intellectual disability was present in 3 individuals.

Sturznickel et al. (2021) reported 3 stillborn sibs, born to nonconsanguineous parents of German origin, with osteogenesis imperfecta type XX. Gestational age of the stillbirths was 26, 22, and 14 weeks. All 3 stillbirths occurred after prenatal diagnosis of a skeletal disorder was made during the second trimester. Findings included a triangular face, blue sclerae, retrognathia, micromelia, angulated long bones, and bilateral clubfeet. The thorax was narrow, resulting in severe lung hypoplasia and congestion of the venous inflow tract of the heart, with consequent hepatomegaly and fetal hydrops. Multiple rib fractures and overtubulation of the long bones were seen on fetal autopsy. One of the stillbirths had a double kidney. Histologic evaluation showed impaired osseous development with altered osteocyte morphology and reduced canalicular connectivity. Examination of bone mineral density distribution showed an impaired and more heterogeneous matrix mineralization in the patients.


Inheritance

The transmission pattern of OI20 in the families reported by Moosa et al. (2019) was consistent with autosomal recessive inheritance.


Molecular Genetics

In 5 probands with a progressive deforming type of osteogenesis imperfecta, who were negative for mutation in known OI-associated genes, Moosa et al. (2019) performed whole-exome sequencing and identified homozygosity for mutations in the MESD gene (607783.0001-607783.0004). The unaffected parents were heterozygous for the mutations, which were not common polymorphisms in public variant databases.

In 3 stillborn sibs with OI20, who were born to nonconsanguineous parents of German origin, Sturznickel et al. (2021) identified compound heterozygous mutations in the MESD gene, the previously identified 5-bp deletion (c.607_611del; 607783.0004) and a novel 1-bp deletion (c.265del; 607783.0005). Each parent was heterozygous for one of the disease-causing variants. Sequencing of the mRNA from the parents revealed a complete loss of the mRNA harboring the c.265del mutation, whereas the mRNA with the c.607_611del mutation was readily detected. The authors suggested that the prenatally lethal phenotype in this family was likely related to complete functional loss of one MESD allele, which could not be compensated by the residual function of the second allele.


REFERENCES

  1. Moosa, S., Yamamoto, G. L., Garbes, L., Keupp, K., Beleza-Meireles, A., Moreno, C. A., Valadares, E. R., de Sousa, S. B., Maia, S., Saraiva, J., Honjo, R. S., Kim, C.-A., and 21 others. Autosomal-recessive mutations in MESD cause osteogenesis imperfecta. Am. J. Hum. Genet. 105: 836-843, 2019. [PubMed: 31564437] [Full Text: https://doi.org/10.1016/j.ajhg.2019.08.008]

  2. Sturznickel, J., Jahn-Rickert, K., Zustin, J., Hennig, F., Delsmann, M. M., Schoner, K., Rehder, H., Kreczy, A., Schinke, T., Amling, M., Kornak, U., Oheim, R. Compound heterozygous frameshift mutations in MESD cause a lethal syndrome suggestive of osteogenesis imperfecta type XX. J. Bone Miner. Res. 36: 1077-1087, 2021. [PubMed: 33596325] [Full Text: https://doi.org/10.1002/jbmr.4277]


Contributors:
Sonja A. Rasmussen - updated : 01/31/2023

Creation Date:
Marla J. F. O'Neill : 10/25/2019

Edit History:
alopez : 04/17/2024
carol : 02/29/2024
carol : 01/31/2023
carol : 01/22/2020
carol : 10/28/2019
alopez : 10/25/2019