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. 2020 Feb 27;106(3):338–355. doi: 10.1016/j.ajhg.2020.01.018

Figure 2.

Figure 2

Individuals Harboring Variants in Either GEFD1 or Spectrin Domains Show Distinct Neurodevelopmental Phenotypes

(A) Percentage of affected individuals with different levels of learning difficulties in either spectrin domain (group 1) or GEFD1 (group 2) mutation cases. 75% of group 2 individuals have mild-moderate learning difficulties. 78% of group 1 individuals have severe learning difficulties.

(B) Early developmental milestones (sitting unsupported, walking, and first words) are delayed in both group 1 and group 2 individuals, but group 1 individuals are affected more severely. For statistical analysis, refer to Table S3. Walking: ∗p = 0.035.

(C) Height and weight standard deviations from mean in either group 1 or group 2 individuals. The median height for group 1 individuals with spectrin mutations was −1.69 SD, and for group 2 individuals with GEFD1 mutations it was −1.34 SD. 33% of the individuals in group 1 and 14% of individuals in group 2 had a height SD of greater than −2 SD, which is often considered as short stature. Weight SD was also reduced in both groups.

(D) Microcephaly was seen in 100% of group 2 individuals, who had a mean OFC of −3.82 SD (median OFC of −3.8 SD). Individuals within group 1 present with macrocephaly. 78% had an OFC greater than 2 SD from the mean; mean OFC was +2.6 SD, median OFC was + 2.7 SD, and OFC range was between +0.7 SD and +4.7 SD. ∗∗p < 0.001 (Table S3)

(E) A neurobehavioral phenotype was observed in 19 out of the 24 (79%) individuals described in this study.

(F) Recurrent behavioral features include stereotypies (6/24 patients), poor attention (14/24 individuals), obsessive-compulsive traits (9/24 individuals), and aggression (8/24 individuals). In total, 2/24 were identified as social or friendly.

(G and H) Quantitative facial phenotyping. t-distributed stochastic neighbor embedding (t-SNE) plot of the vectors of individuals with alterations in GEFD1 and the seventh spectrin domain and the matched controls with intellectual disability. The statistically significant clustering of individuals with mutations in the spectrin domain indicates a recognizable facial phenotype.