Chromosome 8p23.1 deletion

Deletion 8p23.1 involves a partial deletion of the short arm of chromosome 8 and is characterized by low birth weight, postnatal growth deficiency, mild intellectual disability, hyperactivity, craniofacial abnormalities, and congenital heart defects. The prevalence is unknown, but 8p23.1 deletions are rare. To date, more than 50 cases of interstitial or terminal 8p23.1 deletions have been reported, with no significant sex differences.

Diagnosis

Diagnosis is based on clinical manifestations leading to chromosomal analysis. Standard karyotyping often misses 8p23.1 deletions, which are usually detected by molecular karyotyping. Molecular techniques such as FISH, MLPA, and aCGH can be used for genetic characterization of the deletion. The 8p23.1 deletion likely arises through non‑allelic homologous recombination mediated by flanking low‑copy repeats (LCRs), explaining the common size of approximately 3.4 Mb. Congenital heart defects and diaphragmatic hernia are most likely explained by haploinsufficiency of GATA4.

Differential diagnosis includes 22q11 monosomy (velocardiofacial syndrome; see this term). Precise chromosomal analysis confirms the differential diagnosis. Prenatal diagnosis is possible by amniocentesis or chorionic villus sampling with subsequent molecular cytogenetic analysis.

In most cases, this syndrome occurs de novo. However, parents may carry and transmit a chromosomal rearrangement to their children with a 50% risk for each child. Life expectancy is considered normal, provided that no congenital heart anomaly or diaphragmatic hernia is present.

Symptoms

Clinical manifestations are variable and do not depend on the size of the deletion, as it is similar in most patients. The most common features include prenatal and postnatal growth retardation, low birth weight, mild to moderate intellectual disability, psychomotor delay, poor speech, epileptic seizures, and behavioral problems such as hyperactivity and impulsivity. Common craniofacial abnormalities include microcephaly, a high and narrow forehead, broad nasal bridge, epicanthal folds, a high arched palate, short neck, and low‑set ears of unusual shape. In addition, congenital heart defects (atrioventricular defects, septal defects, pulmonary defects, pulmonary stenosis), congenital diaphragmatic hernia, and in boys cryptorchidism and hypospadias have frequently been reported. Normal intelligence has been reported in some affected individuals.

Therapy

This includes assessment, treatment, and regular follow‑up by appropriate specialists, including a general practitioner, pediatrician, and cardiologists. Early diagnosis and access to major developmental therapies aiming at obtaining the best developmental outcome have been proven beneficial.

• spomalenie prenatálneho a postnatálneho rastu
• nízka pôrodná hmotnosť
• mierny až stredný intelektuálny deficit
• psychomotorická retardácia, slabá reč
• epileptické záchvaty
• problémy so správaním, ako je hyperaktivita a impulzívnosť
• mikrocefália, vysoké a úzke čelo, široký nosový mostík, epikantické ryhy, vysoké klenuté podnebie, krátky krk a nízko nasadené uši neobvyklého tvaru
• časté vrodené srdcové chyby (atrioventrikulárne, septa, defekty pľúc, stenóza pľúc)
• vrodená diafragmatická hernia
• u chlapcov kryptorchizmus a hypospadie