ESPE Abstracts (2019) 92 P1-168

Genotype-Phenotype Characteristics in Four Families of Type II Collagenopathy in Our Hospital

Kenichi Yamamoto, Takuo Kubota, Shinji Takeyari, Yukako Nakano, Hirofumi Nakayama, Makoto Fujiwara, Yasuhisa Ohata, Taichi Kitaoka, Yoko Miyoshi, Keiichi Ozono

Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan

Type II collagenopathy is a generic name of the skeletal dysplasia caused by COL2A1 gene, such as achondrogenesis type II, spondyloepiphyseal dysplasia (SEDC), spondyloepimetaphyseal dysplasia (SEMD). Since this is a rare disease, genotype-phenotype characteristics is still unclear. Here, we describe the genotype-phenotype characteristics of four families of type II collagenopathy in our hospital. Family 1: the proband was 2-year-old girl. She showed severe short statute (-4.1 SD), flat nose, platyspondyly, barrel chest and femoral epiphysis enlargement. SEDC was suspected. Her father and her younger sister also showed the same phenotype. Novel heterozygous splice site mutation. (c.3436-2 A>G) was identified in the family. Family 2: the proband was 2-month-old boy. He presented short limbs in the prenatal period and presented flat nose, short statue (-5.0 SD), platyspondyly, hypoplastic ileum and delayed ossification of the pubis and femur at the first visit. SEDC or SEMD was suspected. His parents presented no symptoms. The heterozygous mutation (c.3121 A>G) was found in the proband. This is a glycine substitution mutation. Family 3: 6-year-old boy and 4-yeae-old girl had flat noses, small jaws, severe short statues (-8.5 SD and -10.0 SD) and short limbs. They presented respiratory distress at birth. Their radiograph showed small chest, oval vertebra, hypoplastic ileum, delayed ossification of pubis and dumb-bell like femurs and humerus. SEMD or Knist dysplasia was suspected. The heterozygous mutation (c.3121 A>G) was found in the two patients. This is also a glycine substitution mutation. Family 4: the proband was a boy one day after birth. He presented short limbs in the prenatal period. At birth, mild respiratory distress was presented. He showed hyperterolism, mid face hypoplasia, short trunk short statue (-4.0 SD), platyspondyly, hypoplastic ileum and delayed ossification of the pubis and femur. Hypochondroplasia was suspected, and he was treated with growth hormone. The novel heterozygous carboxyl-terminal region mutation (c.4454G>C) was detected in the proband. Although the splice site mutation was associated with mild phenotype, such as Stickler syndrome, family 1 was severe short statue. The glycine substitution in triple helix of type 2 collagen is related with severe phenotype. Thus, both family 2 and 3 presented severe short statue, but the severity was different. While a C-terminal region mutation was identified in platyspondylic lethal skeletal dysplasia Torrance type, other phenotypes have been reported like family 4. It is important to assess not only the phenotype but also the genotype in a medical examination of type II collagenopathy