Tatton-Brown-Rahman Syndrome (TBRS)

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MedlinePlus Genetics: ⁴² DNMT3A overgrowth syndrome is a disorder characterized by faster than normal growth before and after birth, subtle differences in facial features, and intellectual disability.Individuals with DNMT3A overgrowth syndrome are often longer than normal at birth and are taller than their peers throughout life. Many affected individuals become overweight in late childhood or adolescence. They may also have an abnormally large head size (macrocephaly).The characteristic facial appearance of individuals with DNMT3A overgrowth syndrome includes a round face; thick, horizontal eyebrows; and narrowed openings of the eyes (narrowed palpebral fissures). Additionally, the upper front teeth are often larger than normal.Intellectual disability in DNMT3A overgrowth syndrome ranges from mild to severe. Individuals may have features of autism spectrum disorder, which are characterized by impaired communication and socialization skills.Individuals with DNMT3A overgrowth syndrome may have other signs and symptoms, including a rounded upper back that also curves to the side (kyphoscoliosis), heart defects, flat feet (pes planus), weak muscle tone (hypotonia), or joints that are loose and very flexible (hypermobile joints). Psychological disorders such as depression, anxiety, or obsessive-compulsive disorder can also occur in this disorder.

MalaCards based summary: Tatton-Brown-Rahman Syndrome, also known as dnmt3a overgrowth syndrome, is related to overgrowth syndrome and adult syndrome. An important gene associated with Tatton-Brown-Rahman Syndrome is DNMT3A (DNA Methyltransferase 3 Alpha), and among its related pathways/superpathways are One-carbon metabolism and related pathways and Chromatin Regulation / Acetylation. The drugs Nutmeg and Norethisterone have been mentioned in the context of this disorder. Affiliated tissues include myeloid, bone marrow and prostate, and related phenotypes are macrocephaly and proportionate tall stature

OMIM®: ⁵⁷ Tatton-Brown-Rahman syndrome (TBRS) is characterized by tall stature, a distinctive facial appearance, and impaired intellectual development (Tatton-Brown et al., 2014). Some patients may have increased susceptibility to the development of acute myeloid leukemia (AML; 601626), particularly if they have DNMT3A mutations affecting the R882 residue (Hollink et al., 2017). (615879) (Updated 08-Dec-2022)

UniProtKB/Swiss-Prot: ⁷³ An overgrowth syndrome characterized by a distinctive facial appearance, tall stature and intellectual disability. Facial gestalt is characterized by a round face, heavy horizontal eyebrows and narrow palpebral fissures. Less common features include atrial septal defects, seizures, umbilical hernia, and scoliosis.

Orphanet: ⁵⁸ A rare multiple congenital anomalies syndrome characterized by greater hight, mild to moderate intellectual disability and distinctive facial appereance like round face, heavy, horizontal eyebrows and narrow palpebral fissures.

Disease Ontology: ¹¹ A syndromic intellectual disability characterized by tall stature, a distinctive facial appearance, and impaired intellectual development that has material basis in heterozygous mutation in DNMT3A on chromosome 2p23.3.

Clinical features from OMIM®:

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