A number sign (#) is used with this entry because of evidence that onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome (OORS) is caused by homozygous mutation in the PIGF gene (600153) on chromosome 2p21.

Onychodystrophy, osteodystrophy, impaired intellectual development, and seizures syndrome (OORS) is an autosomal recessive syndromic developmental disorder characterized by global developmental delay with impaired intellectual development, dysmorphic facial features, and hypoplastic terminal phalanges and nails. Patients have seizures or tonic posturing. The disorder is associated with a defect in GPI anchoring of membrane-bound proteins (summary by Salian et al., 2021).

For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).

See also DOORS syndrome (220500), which shows some overlapping clinical features.

Salian et al. (2021) reported 2 unrelated children, each born of consanguineous Indian parents, with a similar syndromic neurodevelopmental disorder. Patient 1 was a 14-year-old boy with developmental delay, severely impaired intellectual development with no effective speech, hypoplastic fingernails, toenails, and terminal phalanges, and dysmorphic facial features, including delayed permanent dentition, small teeth, anteverted nares, low-set pinnae, anteverted earlobes, full lips, and open mouth. Other features included atrial septal defect, refractory generalized tonic-clonic seizures, and precocious puberty. He had no toilet control and displayed head banging and repetitive nonpurposeful rocking movements of the head. Patient 2 was a 13-month-old girl with poor overall growth, microcephaly (-3.2 SD), global developmental delay with poor eye contact, hypoplastic or absent finger and toenails, and triphalangeal thumb. Dysmorphic features included micrognathia, microstomia, coarse face, and short nose. She had tonic posturing without overt seizures. Neither patient had deafness, and brain imaging was normal. Patient 1 had a similarly affected brother who died before 2 years of age. The authors noted the phenotypic overlap with DOORS syndrome (220500), with the notable lack of deafness in their patients.

The transmission pattern of OORS syndrome in the families reported by Salian et al. (2021) was consistent with autosomal recessive inheritance.

In 2 unrelated children with OORS syndrome, each born of consanguineous Indian parents, Salian et al. (2021) identified a homozygous missense mutation in the PIGF gene (P172R; 600153.0001). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. Flow cytometric analysis of patient cells showed defective GPI anchor biosynthesis that could be restored by expression of wildtype PIGF. Additional functional studies in PIGF-deficient CHO cells showed that the mutant enzyme had low-residual activity compared to wildtype, although levels of the mutant protein were normal. The findings were consistent with PIGF deficiency.