Entry - #617952 - OSTEOGENESIS IMPERFECTA, TYPE XVIII; OI18 - OMIM
# 617952

OSTEOGENESIS IMPERFECTA, TYPE XVIII; OI18


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
6q14.1 Osteogenesis imperfecta, type XVIII 617952 AR 3 TENT5A 611357
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Face
- High broad forehead
- Grooved philtrum
- Micrognathia
Eyes
- Blue sclerae
- Long eyelashes
Nose
- Broad nasal root
Teeth
- Abnormal teeth (rare)
CHEST
Ribs Sternum Clavicles & Scapulae
- Thin ribs
- Clavicular fractures
ABDOMEN
External Features
- Umbilical hernia (rare)
SKELETAL
- Poor mineralization
- Multiple spontaneous fractures
- Thin cortex of bones
Skull
- Wormian bones
Spine
- Vertebral collapse
- Codfish vertebrae
Limbs
- Bowing of long bones
- Joint laxity
NEUROLOGIC
Central Nervous System
- Motor developmental delay
- Speech delay
MOLECULAR BASIS
- Caused by mutation in the family with sequence similarity 46, member A gene (FAM46A, 611357.0001)
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 II AD 3 166210 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type III AD 3 259420 COL1A2 120160
7q21.3 Osteogenesis imperfecta, type IV AD 3 166220 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 XVIII (OI18) is caused by homozygous mutation in the FAM46A gene (TENT5A; 611357) on chromosome 6q14.


Description

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


Clinical Features

Doyard et al. (2018) reported 2 sibs and 2 unrelated patients with osteogenesis imperfecta and mutations in the FAM46A gene. The first patient was an Italian boy who was born with bowing of the femora and tibia, but also experienced swallowing difficulties and hyperthermic episodes in the first 6 months of life. He was originally diagnosed with Stuve-Wiedemann syndrome (601559), but his symptoms later became more consistent with a diagnosis of OI, with 4 spontaneous fractures and vertebral collapses in the first 2 years of life. He also had blue sclerae and abnormal teeth. He died suddenly and inexplicably at 4 years of age. A French brother and sister, born to first-cousin parents, showed bowing of the femora, poor mineralization, thin cortical bone, and numerous wormian bones at birth. They sustained numerous fractures in the first years of life, and also exhibited blue sclerae and joint hyperlaxity. The girl and her mother both had a marfanoid habitus, with arachnodactyly and joint hyperlaxity, but no cardiovascular abnormalities; the mother had no ocular abnormalities. The fourth patient was an Egyptian girl born to double-first-cousin parents, who presented at 5 years of age with a history of recurrent spontaneous fractures, approximately 7 per year. Dysmorphic features included high broad forehead, long eyelashes, wide palpebral fissures, blue sclerae, grooved philtrum, broad nasal root, and micrognathia. She also had joint laxity and an umbilical hernia. X-ray examination showed generalized osteoporotic texture, collapse of the lower 3 thoracic and first lumbar vertebral bodies with biconcave endplates (codfish vertebrae), thin ribs, bowing of long bones, thin cortex, multiple fractures, and wormian bones at the skull base. An older sister who was born with severe bowing of upper and lower limbs died of pneumonia at 3 months of age. The French sibs showed developmental delay, with speech delay in the brother and global hypotonia and motor delay in the sister; the Egyptian girl had motor developmental delay.


Inheritance

The transmission pattern of OI18 in the families reported by Doyard et al. (2018) was consistent with autosomal recessive inheritance.


Molecular Genetics

In an Italian boy who exhibited features of Stuve-Wiedemann syndrome but was negative for mutation in the LIFR gene (151443), and who later developed symptoms consistent with OI, Doyard et al. (2018) performed exome sequencing and identified homozygosity for a frameshift mutation in the FAM46A gene (611357.0001). Screening the FAM46A gene in 25 patients with OI who were negative for mutation in known OI-associated genes revealed homozygosity for missense mutations in a French brother and sister (H127R; 611357.0002) and an Egyptian girl (D231G; 611357.0003).


REFERENCES

  1. Doyard, M., Bacrot, S., Huber, C., Di Rocco, M., Goldenberg, A., Aglan, M. S., Brunelle, P., Temtamy, S., Michot, C., Otaify, G. A., Haudry, C., Castanet, M., Leroux, J., Bonnefont, J.-P., Munnich, A., Baujat, G., Lapunzina, P., Monnot, S., Ruiz-Perez, V. L., Cormier-Daire, V. FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta. J. Med. Genet. 55: 278-284, 2018. [PubMed: 29358272, related citations] [Full Text]


Creation Date:
Marla J. F. O'Neill : 04/30/2018
carol : 12/01/2022
carol : 04/30/2018

# 617952

OSTEOGENESIS IMPERFECTA, TYPE XVIII; OI18


DO: 0111848;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
6q14.1 Osteogenesis imperfecta, type XVIII 617952 Autosomal recessive 3 TENT5A 611357

TEXT

A number sign (#) is used with this entry because of evidence that osteogenesis imperfecta type XVIII (OI18) is caused by homozygous mutation in the FAM46A gene (TENT5A; 611357) on chromosome 6q14.


Description

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


Clinical Features

Doyard et al. (2018) reported 2 sibs and 2 unrelated patients with osteogenesis imperfecta and mutations in the FAM46A gene. The first patient was an Italian boy who was born with bowing of the femora and tibia, but also experienced swallowing difficulties and hyperthermic episodes in the first 6 months of life. He was originally diagnosed with Stuve-Wiedemann syndrome (601559), but his symptoms later became more consistent with a diagnosis of OI, with 4 spontaneous fractures and vertebral collapses in the first 2 years of life. He also had blue sclerae and abnormal teeth. He died suddenly and inexplicably at 4 years of age. A French brother and sister, born to first-cousin parents, showed bowing of the femora, poor mineralization, thin cortical bone, and numerous wormian bones at birth. They sustained numerous fractures in the first years of life, and also exhibited blue sclerae and joint hyperlaxity. The girl and her mother both had a marfanoid habitus, with arachnodactyly and joint hyperlaxity, but no cardiovascular abnormalities; the mother had no ocular abnormalities. The fourth patient was an Egyptian girl born to double-first-cousin parents, who presented at 5 years of age with a history of recurrent spontaneous fractures, approximately 7 per year. Dysmorphic features included high broad forehead, long eyelashes, wide palpebral fissures, blue sclerae, grooved philtrum, broad nasal root, and micrognathia. She also had joint laxity and an umbilical hernia. X-ray examination showed generalized osteoporotic texture, collapse of the lower 3 thoracic and first lumbar vertebral bodies with biconcave endplates (codfish vertebrae), thin ribs, bowing of long bones, thin cortex, multiple fractures, and wormian bones at the skull base. An older sister who was born with severe bowing of upper and lower limbs died of pneumonia at 3 months of age. The French sibs showed developmental delay, with speech delay in the brother and global hypotonia and motor delay in the sister; the Egyptian girl had motor developmental delay.


Inheritance

The transmission pattern of OI18 in the families reported by Doyard et al. (2018) was consistent with autosomal recessive inheritance.


Molecular Genetics

In an Italian boy who exhibited features of Stuve-Wiedemann syndrome but was negative for mutation in the LIFR gene (151443), and who later developed symptoms consistent with OI, Doyard et al. (2018) performed exome sequencing and identified homozygosity for a frameshift mutation in the FAM46A gene (611357.0001). Screening the FAM46A gene in 25 patients with OI who were negative for mutation in known OI-associated genes revealed homozygosity for missense mutations in a French brother and sister (H127R; 611357.0002) and an Egyptian girl (D231G; 611357.0003).


REFERENCES

  1. Doyard, M., Bacrot, S., Huber, C., Di Rocco, M., Goldenberg, A., Aglan, M. S., Brunelle, P., Temtamy, S., Michot, C., Otaify, G. A., Haudry, C., Castanet, M., Leroux, J., Bonnefont, J.-P., Munnich, A., Baujat, G., Lapunzina, P., Monnot, S., Ruiz-Perez, V. L., Cormier-Daire, V. FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta. J. Med. Genet. 55: 278-284, 2018. [PubMed: 29358272] [Full Text: https://doi.org/10.1136/jmedgenet-2017-104999]


Creation Date:
Marla J. F. O'Neill : 04/30/2018

Edit History:
carol : 12/01/2022
carol : 04/30/2018