The distinctive gestalt of the CDK13-related developmental disorder is grossly independent from ethnical variance

We present the craniofacial clinical photographs of an 8-year-old girl born to non-consanguineous, healthy parents from sub-Saharan Africa, with a heterozygous CDK13 variant NM_003718.4: c.2149G>A, p.(Gly717Arg), ACMG class 5, known to cause the Congenital Heart Defects, Facial dysmorphism and Intellectual Developmental Disorder (CHDFIDD, MIM## 617360). She presented with multiple congenital cardiac defects (two atrial septum defects, a muscular ventricular septal defect and peripheral pulmonary stenosis), hypotonia, dysphagia, myopia, and left duplex renal collecting system. At 6 years of age, growth parameters were: weight 18.5 kg (−1.45 SD), height 111 cm (−1.95 SD), and head circumference 49.5 cm (−1.67 SD). She had global developmental delay; walked independently by 4 years with a broad-based gait, spoke single words by 5 years, displayed echolalia, and she was diagnosed with severe intellectual disability by 7 years. Brain MRI revealed complete agenesis of the corpus callosum. Spinal MRI, EEG and hearing tests showed normal results.
She shares the CDK13-related recognizable gestalt characterized by widely arched eyebrows, epicanthus, pronounced hypertelorism, wide nasal bridge and small, low-set and posteriorly angulated ears; with the sole exception of full lips which is also the only discordant feature in the single other, apparently sub-Saharan African, affected child described previously [Bostwick et al., ID 1008].
Whilst there is a global aim to improve the clinical application of reference datasets by increasing their diversity, our case demonstrates that ethnical variance does not modify significantly one of the major diagnostic features of a rare genetic syndrome.
We hypothesize that the CDK13-related phenotypic consistency may be more dependent on a similar degree of gain-of-function considering that pathogenic missense CDK13 variants cluster within the protein kinase domain of the corresponding protein.