Congenital Disorder Of Glycosylation, Type Iig

A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type IIg (CDG2G) is caused by homozygous mutation in the COG1 gene (606973) on chromosome 17q25.

For a general discussion of CDG, see CDG1A (212065).

Clinical Features

Foulquier et al. (2006) reported an infant girl who had failure to thrive, generalized hypotonia, growth retardation with rhizomelic short stature, and mild psychomotor retardation. At 21 months of age, she was noted to have progressive microcephaly and mildly enlarged spleen and liver. She was born of third level remotely consanguineous parents. Biochemical studies showed an abnormal isoelectric pattern of serum transferrin, consistent with CDG type II. Studies of ApoC3 (107720) revealed that she had a defect in O-glycosylation as well as N-glycosylation.

Clinical Variability

Zeevaert et al. (2009) reported 2 male patients with a disorder similar to but more severe than the disorder in the patient reported by Foulquier et al. (2006). They described the disorder as a cerebrocostomandibular (CCMS; 117650)-like syndrome. The first boy was born of consanguineous Greek Turkish parents and presented with microcephaly, smooth philtrum, thin upper lip, short neck, low-set posteriorly rotated ears, Pierre-Robin sequence, growth retardation, and bilateral maculopathy. Costovertebral anomalies included osteopenia, rib fusions and posterior rib gaps, butterfly vertebrae, misaligned vertebrae, and clubfoot. ECG showed mild pulmonary hypertension and hypertrophy of the atrial septum, and MRI scan of the brain showed enlarged cisterna magna and hypoplastic vermis. He had mild motor and mental retardation. Biochemical studies revealed an isoelectric pattern of serum transferrin that was consistent with CDG type II. The second boy was born of unrelated Bulgarian parents and presented with shortening of the long bones and facial dysmorphism including downslanting palpebral fissures, wide nasal bridge, hypertelorism, long philtrum, small mouth, micrognathia, high palate, low-set posteriorly rotated ears, and right microtia. Costovertebral anomalies included multiple vertebral segmentation defects and bilateral fusions of ribs. MRI scan of the brain at age 5 years detected atrophy of the temporal cortex and floculonodular lobe of the cerebellum. He had moderate mental retardation. X-ray exam at 6.5 years showed prominent kyphoscoliosis, coxa valga, shallow acetabular roofs, broad necks and small proximal epiphyses of the femur with irregular medial parts.

Reviews

Coman et al. (2008) provided a review of the skeletal manifestations of congenital disorders of glycosylation, which they suggested may be underrecognized.

Molecular Genetics

Foulquier et al. (2006) identified a homozygous mutation in the COG1 gene (606973.0001) in a girl with CDG type II.

Zeevaert et al. (2009) described 2 patients with a cerebrocostomandibular-like syndrome in whom they identified a homozygous splice site mutation in the COG1 gene (606973.0002). Zeevaert et al. (2009) stated that the severe phenotype in these patients compared with the mild phenotype in the patient reported by Foulquier et al. (2006) may be explained by the more severe truncation of the COG1 protein.