Figure 1.

Phenotypes of Affected Individuals

(A) The pedigrees of families with PIGB mutations. In family 5, the unaffected siblings were genotyped, and none were compound heterozygous. However, the family does not wish their carrier status to be published.

(B) Photographs of affected individuals. Individual 2A at 9 years old (note a wide nasal bridge, a long and smooth philtrum, a thin upper lip, a horizontal chin crease, and upturned earlobes), 2B at 11 months old (note similar features), individual 5 at 20 years old (note a horizontal chin crease, a prominent philtrum, and slightly upturned earlobes), individual 7 at 8 months old (note a wide nasal bridge, brachytelephalangy, and nail hypoplasia), individual 8A at birth (note a wide nasal bridge, a long and smooth philtrum, and a thin upper lip), individual 10A at birth, and individual 10B at 2.5 months old (note for both hypertrichosis, a wide nasal bridge, coarse facial features, a long and smooth philtrum, a pointed chin with a horizontal crease, uplifted earlobes, and toe and nail hypoplasia).

(C) EEG findings for individual 4. The top left panel depicts a sleep EEG at 9 months old, before any treatment; diffuse, low-voltage fast waves seem to be characteristic in this individual. Spindle waves are observed. High-amplitude slow waves are sometimes seen at the frontal regions predominantly. The top right panel depicts a sleep EEG at 30 months old; there are 0.5 s 12 Hz rhythmic waves at the frontal region and very small spike and high-voltage slow wave complexes. There is also a paucity of sleep markers and bilateral central spikes. The bottom left panel depicts a sleep EEG at 3 years and 10 months old. Generalized spike and wave discharge followed by voltage attenuation were seen. In the bottom right pictures, brain MRI did not demonstrate any brain anomalies such as dysplasia, atrophy, or delayed myelination.

(D) Radiographs of the hands and feet of individual 10B at 2.5 months of age showing aplasia of the terminal phalange of the fifth finger bilaterally and hypoplasia or aplasia of the terminal phalanges of the toes.

(E) MRI of individual 9A at 2 years and 3 months old. The left image depicts an axial T-2 sequence showing diffuse cerebral volume loss characterized by widening of the ventricles and extra CSF spaces with a prominent interhemispheric fissure anteriorly. There is suspicion of polymicrogyria along the bilateral occipital lobes, more pronounced on the right. The right image depicts an axial FLAIR sequence showing diffuse cerebral volume loss. There were signs of hypomyelination with a hyperintense signal in peri-ventricular and subcortical white matter, more pronounced at the occipital and frontal lobes bilaterally.