Conditions Treated

In the Epigenetic Syndromes Clinic, we are initially focusing on the following four conditions; however, we will see and follow any patient with other congenital epigenetic disorders (CEDs) as shown in the list below.

All conditions involve problems with how the body uses our large recipe book or instruction manual, DNA. Genes involved in congenital epigenetic disorders change the body’s ability to turn on and off important recipes or genes during development and throughout a person’s lifetime. The exact mechanism for the genetic defect varies from condition to condition.

Rubinstein-Taybi Syndrome

Rubinstein-Taybi syndrome is a genetic condition caused by a problem with either the CREBBP or EP300 genes. These genes can be thought of as recipes the body uses to help maintain normal body development and function. When these recipes are not used correctly, different symptoms can be seen, though not in everyone. Individuals with Rubinstein-Taybi syndrome (RTS) typically have distinctive facial features, broad thumbs and great toes, small size with difficulty growing, and varying degrees of learning problems. They tend to communicate well, though at times with assistive devices, and are usually very friendly and sociable. Certain birth defects and complications as the individuals age can occur. Management for RTS is complex and should be managed by a team that knows the syndrome well.

Kabuki Syndrome

Kabuki syndrome (KS) is a genetic condition caused by a problem in either the KMT2D or KDM6A genes. These genes can be thought of as recipes the body uses to help maintain normal body development and function. Individuals with KS typically have distinctive facial features and varying degrees of developmental and intellectual problems but also have associated medical problems. Individuals with KS are at risk for recurrent infections and can have significant impacts to their infection fighting cells. They are also at a higher risk for autoimmune disorders. Individuals also can have changes to their bones with an increased risk of scoliosis. Management for KS is complex and should be managed by a team that knows the syndrome well.

Menke-Hennekam Syndrome

Menke-Hennekan syndrome (MKHK) is also caused by a problem with either the CREBBP or EP300 genes in a different area of the gene or recipe than what causes Rubinstein-Taybi syndrome. Individuals with MKHK have varying degrees of developmental disability and intellectual disability with some individuals having autism or autistic-like features, visual impairment, hearing impairment, feeding problems and recurrent respiratory infections. Rarely, some individuals have shown seizures and scoliosis. Individuals with MKHK have been seen to have an increased risk of some birth defects including changes to the palate, heart, kidneys, intestines, testicles, bones and brain. Individuals should be monitored for complications such as hypermobility-related injury and scoliosis. Management for MKHK is complex and should be managed by a team that knows the syndrome well.

KAT6A Syndrome

KAT6A syndrome, also known as Arboleda-Tham syndrome, is caused by a problem in the KAT6A gene. This gene can be thought of as an important recipe the body uses to help maintain normal body development and function. Individuals with KAT6A syndrome have severe speech apraxia, which affects a person’s ability to communicate and express themselves in conversation with others. Additionally, individuals have an increased risk for low muscle tone, feeding problems, constipation, recurrent infections and eye problems. There are some individuals that have seizures and sleep disorders. Birth defects have been seen and include changes to the heart and brain. Management for KAT6A syndrome is complex and should be managed by a team that knows the syndrome well.

Currently Known Congenital Epigenetic Disorders (Known Genes)

• ADNP syndrome AKA Helsmoortel-Van der Aa syndrome (ADNP)
• ATRX-related intellectual disability syndrome (ATRX)
• CHD-related autism spectrum disorder (CHD8)
• Autosomal dominant intellectual disability 1 (MBD5)
• Autosomal dominant intellectual disability 23 (SETD5)
• Autosomal dominant intellectual disability 30 (ZMYND11)
• Autosomal dominant intellectual disability 32 AKA Arboleda-Tham syndrome (KAT6A)
• Borjeson-Forssman-Lehmann syndrome (PHF6)
• Brachydactyly MR syndrome (HDAC4)
• Cerebellar ataxia, deafness and narcolepsy (DNMT1)
• Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly and microphthalmia (HDAC6)
• Cleft palate, psychomotor retardation and distinctive facial features (KMD1A)
• Coffin-Lowry syndrome (RPS6KA3, aka RSK2)
• Coffin-Siris syndrome 1 (ARID1B)
• Coffin-Siris syndrome 4 (SMARCA4)
• Cornelia de Lange syndrome (HDAC8, NIPBL, SMZC1A, SMCZ3)
• Epileptic encephalopathy (CHD2)
• Floating-Harbor syndrome (SRCAP)
• Genitopatellar syndrome (KAT6B)
• Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (DNMT3B)
• Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ZBTB24)
• Immunodeficiency-centromeric instability-facial anomalies syndrome 3 (CDCA7)
• Immunodeficiency-centromeric instability-facial anomalies syndrome 4 (HELLS)
• Kabuki syndrome type 1 (KMT2D)
• Kabuki syndrome type 2 (KDM6A)
• KAT6A syndrome AKA Arboleda-Tham syndrome (KAT6A)
• Kleefstra syndrome 1 (EHMT1)
• KMT2C-related disorder (formerly known as Kleefstra syndrome 2) (KMT2C)
• KMT2E-associated intellectual disability (KMT2E)
• Luscan-Lumish syndrome (SETD2)
• Menke-Hennekam syndrome (CREBBP, EP300)
• Neuropathy, hereditary sensory, type IE (DNMT1)
• Nicolaides-Baraitser syndrome (SMARCA2)
• Oculofasciocardiodental syndrome or syndromic micro-ophthalmia (BCOR)
• Opitz-Kaveggia syndrome (MED12)
• Pilarowski-Bjornsson syndrome (CHD1)
• Progressive supranuclear palsy / frontotemporal dementia (MAPT)
• Rett syndrome (MECP2)
• Rubinstein-Taybi syndrome 1 (CREBBP)
• Rubinstein-Taybi syndrome 2 (EP300)
• Say Barber Biesecker Young Simpson syndrome (KAT6B)
• Schimke immuno-osseous dysplasia (SMARCAL1)
• Schinzel-Giedion (SETBP1)
• SETD1B-related syndrome
• Sifrim-Hitz-Weiss syndrome (CHD4)
• SMARCA2-related blepharophimosis intellectual disability syndrome (SMARCA2)
• Sotos syndrome (NSD1)
• Tatton-Brown-Rahman syndrome (DNMT3A)
• Townes-Brocks syndrome 1 (SALL1)
• Weaver syndrome 2 (EZH2)
• Werner syndrome (WRN)
• Wiedemann-Steiner syndrome (KMT2A)
• White Sutton syndrome (POGZ)
• X-linked intellectual disability 33 (TAF1)
• X-linked intellectual disability 93 (BRWD3)
• X-linked intellectual disability Claes-Jensen type (KDM5C)
• X-linked intellectual disability, Siderius type (PHF8)
• X-linked intellectual disability, Turner type (HUWE1)

Additional Programs at Cincinnati Children’s

There are several epigenetic disorders that are specifically supported by targeted programs at Cincinnati Children’s:

• CHARGE syndrome (CHD7) – The CHARGE Center
• Fragile X (FRX) Program
• Rett Syndrome (MECP2) Program

Conditions Treated by Loren Peña, MD, Division of Human Genetics

• Shashi-Peña syndrome (ASXL2)
• Bainbridge-Ropers syndrome (ASXL3)
• Bohring-Opitz syndrome (ASXL1)

General Genetics Services

The Division of Human Genetics at Cincinnati Children’s is available to see children and adults with a wide range of medical conditions.