Verheij syndrome (VRJS) is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects (summary by Verheij et al., 2009 and Dauber ... Verheij syndrome (VRJS) is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects (summary by Verheij et al., 2009 and Dauber et al., 2013).
Verheij et al. (2009) reported 2 unrelated Dutch children born with multiple and somewhat overlapping congenital anomalies associated with large heterozygous de novo deletions of chromosome 8q24. A 20-month-old boy had delayed psychomotor development, poor growth, seizures, ventricular ... Verheij et al. (2009) reported 2 unrelated Dutch children born with multiple and somewhat overlapping congenital anomalies associated with large heterozygous de novo deletions of chromosome 8q24. A 20-month-old boy had delayed psychomotor development, poor growth, seizures, ventricular septal defect, postaxial polydactyly, and hip dislocation. Dysmorphic features included plagiocephaly, anteverted nares, short columella, high palate, micrognathia, low-set and posteriorly rotated ears, short neck, and coloboma. He also had laryngotracheomalacia. Brain MRI showed hypoplastic corpus callosum, delayed myelination, and cerebral atrophy. The second child was a girl with poor growth, unilateral coloboma, atrial septal defects, clenched thumbs, syndactyly of the hands and feet, metatarsal fusion, unilateral hip luxation, severe failure to thrive, and seizures. Dysmorphic features included triangular ears with flattened helices, prominent nasal tip, and hypoplastic nasal alae. Some features were reminiscent of Langer-Giedion syndrome (150230), but she died at age 11 months from a subdural hematoma before classic features of that syndrome could develop. Dauber et al. (2013) reported 5 unrelated children with 5 different heterozygous de novo interstitial deletions of chromosome 8q24.3; the children were identified from a cohort of patients who underwent array comparative genomic hybridization (aCGH). The 5 children ranged in age from 3 to 17 years, and all had facial dysmorphism and global growth retardation, including 3 with microcephaly; all but 1 had developmental delay. Common dysmorphic facial features included long philtrum, anteverted nares, short nose, thin upper lip, and broad nasal root. More variable features included microretrognathia, coloboma, short neck, preauricular pits, and bitemporal narrowing. All but 1 patient had renal abnormalities, including unilateral renal agenesis, renal hypoplasia, polycystic kidneys, and ectopic renal fusion. Three patients had vertebral abnormalities, such as sacral dysplasia, coccyx agenesis, vertebral fusion, or hemivertebrae, and 4 had joint laxity or hip dislocation. Two patients had cardiac ventricular defects. Dauber et al. (2013) reported a sixth patient with similar features, including severe growth retardation, delayed psychomotor development, microcephaly, (-4.1 SD), dysmorphic facial features, seizures, ventricular septal defect, hip dislocation, hemivertebrae, and scoliosis. Coloboma and renal abnormalities were not present. Exome sequencing of this patient identified a heterozygous de novo missense mutation in the PUF60 gene (H169Y; 604819.0001).