A number sign (#) is used with this entry because of evidence that autosomal dominant intellectual developmental disorder-70 (MRD70) is caused by a specific heterozygous missense mutation (R1740Q) in the SETD2 gene (612778) on chromosome 3p21.

Autosomal dominant intellectual developmental disorder-70 (MRD70) is characterized by mild global developmental delay, moderately impaired intellectual disability with speech difficulties, and behavioral abnormalities. More variable findings may include hypotonia and dysmorphic features (Rabin et al., 2020)

Rabin et al. (2020) reported 3 unrelated patients (group 2) with mild to moderately impaired intellectual development associated with a specific de novo heterozygous mutation in the SETD2 gene (R1740Q; 612778.0006). The patients were ascertained through collaborative efforts after the mutation was identified, and the phenotype was delineated retrospectively. They had mild global developmental delay and speech delay, but all achieved independent walking. Patient 1 was 15-year-old boy who attended a special school, showed behavioral abnormalities, and had a developmental level of a 6-year-old. Dysmorphic features included upslanting palpebral fissures, upslanting straight-lined eyebrows, brachycephaly, fifth finger clinodactyly, and camptodactyly. Patient 2 was a 4.5-year-old boy with poor speech, hypotonia, strabismus, and joint hyperlaxity. Brain imaging was normal. The pregnancy had been complicated by polyhydramnios. Patient 3 was an 8-year-old girl with IQ levels between 67 and 76 and behavioral abnormalities. Notable facial features included high-arched palate, crowded teeth, retrognathia, myopia, malar flattening, and broad eyebrows. She also had hypotonia.

The heterozygous mutations in the SETD2 gene that were identified in patients with MRD70 by Rabin et al. (2020) occurred de novo.

In 3 unrelated patients (group 2) with MRD70, Rabin et al. (2020) identified a de novo heterozygous missense mutation in the SETD2 gene (R1740Q; 612778.0006). The mutation, which was found thorough clinical genetics services, was not present in the gnomAD database. The patients were ascertained through collaborative efforts, and the phenotype determined retrospectively. Functional studies of the variant and studies of patient cells were not performed. The patients had developmental delay with moderately impaired intellectual development, low-normal head circumference, variable and mild dysmorphic features, and absence of additional congenital anomalies or systemic involvement. The phenotype was considered to be different from that of patients with other mutations in the SETD2 gene, including those with a different mutation at the same codon (see R1740W, 612778.0005).