Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome explained

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome
Synonyms:	Intellectual disability-craniofacial anomalies-cardiac defects syndrome, Arboleda-Tham syndrome, KAT6A syndrome, autosomal dominant intellectual disability 32, (obsolete) autosomal dominant mental retardation 32
Symptoms:	Multi-systemic
Complications:	Death with untreated cardiac defects
Onset:	Birth
Duration:	Lifelong
Risk:	-->
Prevention:	None
Management:	-->
Prognosis:	Poor if untreated
Frequency:	Rare, only 78 cases have been described in medical literature.
Deaths:	-

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome is a rare genetic disorder which is characterized by multi-systemic symptoms primarily affecting the intellect and post-natal development.

Signs and symptoms

Symptoms within people with the disorder vary, but they are generally the following:^[1]

Intellectual

• Intellectual disabilities

Developmental

• Widespread developmental delays
• Speech delays (which can sometimes last into adulthood)
• Feeding difficulties

Intestinal

• Acid reflux
• Chronic constipation

Cardiac

• Atrial septal defect
• Ventricular septal defect
• Patent foramen ovale
• Persistent ductus arteriosus

Ocular

• Strabismus
• Amblyopia
• Refractory errors

Facial

• Broad nose
• Thin upper lip
• Bitemporal narrowing
• Microcephaly

Less common symptoms include craniosynostosis, autism, sleep disturbance, epilepsy, recurrent viral infections.

Causes

This condition is caused by heterozygous mutations in the KAT6A gene, in chromosome 8.^{[2] [3]} These mutations are often sporadic, and are either frameshift,^[4] missense, and nonsense.^[5]

Diagnosis

Diagnosis of the disorder is established by gene sequencing.

Epidemiology

According to OMIM,^[6] 78 cases have been described in medical literature.^{[2] [4] [5] [7] [8]}

Notes and References

1. Web site: March 2021 . Dias . Patricia . Neves . Mariana . Autosomal dominant intellectual disability craniofacial anomalies cardiac defects syndrome . 2023-02-15 . . en.
2. Web site: Arboleda-Tham syndrome . 2022-06-24 . yeastgenome.org.
3. Arboleda VA, Lee H, Dorrani N, Zadeh N, Willis M, Macmurdo CF, Manning MA, Kwan A, Hudgins L, Barthelemy F, Miceli MC, Quintero-Rivera F, Kantarci S, Strom SP, Deignan JL, Grody WW, Vilain E, Nelson SF . 6 . De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay . American Journal of Human Genetics . 96 . 3 . 498–506 . March 2015 . 25728775 . 4375619 . 10.1016/j.ajhg.2015.01.017 .
4. Millan F, Cho MT, Retterer K, Monaghan KG, Bai R, Vitazka P, Everman DB, Smith B, Angle B, Roberts V, Immken L, Nagakura H, DiFazio M, Sherr E, Haverfield E, Friedman B, Telegrafi A, Juusola J, Chung WK, Bale S . 6 . Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder . American Journal of Medical Genetics. Part A . 170 . 7 . 1791–1798 . July 2016 . 27133397 . 10.1002/ajmg.a.37670 . 23829096 .
5. Kennedy J, Goudie D, Blair E, Chandler K, Joss S, McKay V, Green A, Armstrong R, Lees M, Kamien B, Hopper B, Tan TY, Yap P, Stark Z, Okamoto N, Miyake N, Matsumoto N, Macnamara E, Murphy JL, McCormick E, Hakonarson H, Falk MJ, Li D, Blackburn P, Klee E, Babovic-Vuksanovic D, Schelley S, Hudgins L, Kant S, Isidor B, Cogne B, Bradbury K, Williams M, Patel C, Heussler H, Duff-Farrier C, Lakeman P, Scurr I, Kini U, Elting M, Reijnders M, Schuurs-Hoeijmakers J, Wafik M, Blomhoff A, Ruivenkamp CA, Nibbeling E, Dingemans AJ, Douine ED, Nelson SF, Hempel M, Bierhals T, Lessel D, Johannsen J, Arboleda VA, Newbury-Ecob R . 6 . KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants . Genetics in Medicine . 21 . 4 . 850–860 . April 2019 . 30245513 . 6634310 . 10.1038/s41436-018-0259-2 .
6. Web site: OMIM Entry - # 616268 - Arboleda-Tham Syndrome . 2022-06-24 . omim.org . en-us.
7. Tham E, Lindstrand A, Santani A, Malmgren H, Nesbitt A, Dubbs HA, Zackai EH, Parker MJ, Millan F, Rosenbaum K, Wilson GN, Nordgren A . 6 . Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features . American Journal of Human Genetics . 96 . 3 . 507–513 . March 2015 . 25728777 . 4375419 . 10.1016/j.ajhg.2015.01.016 .
8. Lin YF, Lin TC, Kirby R, Weng HY, Liu YM, Niu DM, Tsai SF, Yang CF . 6 . Diagnosis of Arboleda-Tham syndrome by whole genome sequencing in an Asian boy with severe developmental delay . Molecular Genetics and Metabolism Reports . 25 . 100686 . December 2020 . 33318932 . 7723794 . 10.1016/j.ymgmr.2020.100686 .