知的障害を伴う7種の微小欠失・重複疾患

What Are Microdeletion and Microduplication Syndromes (Designated Intractable Diseases)?

Microdeletion and microduplication syndromes are genetic conditions caused by the deletion or duplication of genes at specific locations on a chromosome.

As the term “micro” suggests, these alterations are small in size, with some spanning as few as 500,000 base pairs. Typically, they are said to result from the loss or gain of sequences ranging from 500,000 to 3,000,000 base pairs. Depending on the size and precise location of the variant, it can lead to a diverse spectrum of clinical symptoms and varying levels of severity, often accompanied by developmental delays such as intellectual disabilities. Furthermore, the vast majority of microdeletion and microduplication syndromes occur sporadically (de novo) and are widely recognized to arise independently of maternal age.

Consequently, it cannot be definitively claimed that screening for these conditions is without clinical value, regardless of whether the pregnant individual is young or of advanced maternal age.

What is the Highly Frequent DiGeorge Syndrome (Designated Intractable Disease 203)?

DiGeorge Syndrome (Designated Intractable Disease 203) is a genetic condition caused by a deletion in a specific region of chromosome 22. This syndrome is known to cause a wide range of manifestations, including immune system problems, heart defects, and characteristic facial differences. Although it is a relatively rare condition, it can have serious implications for affected individuals and their families.

Detection Track Record via Hiro Clinic’s NIPT Screenings

From 3,322 screenings conducted at Hiro Clinic, 5 cases of genetic abnormalities associated with DiGeorge Syndrome were identified. This frequency—approximately 1 in 600 cases—is significantly higher than the general epidemiological data of 1 in 4,000 to 6,000 individuals, demonstrating the high detection capability of DiGeorge Syndrome (Designated Intractable Disease No. 203). This outcome strongly supports Hiro Clinic’s advocacy for the clinical importance of microdeletion and microduplication screening. Particularly for pregnant individuals and families considered to be at a higher genetic risk, this screening provides vital information that enables early intervention and preparation.

Microdeletion and Microduplication Syndromes Screenable via Hiro Clinic NIPT

In terms of the population currently living with the condition, DiGeorge Syndrome (Designated Intractable Disease 203) is said to be the second most common after Down syndrome. This is thought to be correlated with its relatively favorable life prognosis. Including DiGeorge syndrome, Hiro Clinic NIPT can screen for a total of 143 types of microdeletion and microduplication syndromes. All testing procedures are conducted domestically within Japan.

Screening Track Record at Hiro Clinic

Hiro Clinic, which has performed over 75,000 NIPT (Non-Invasive Prenatal Testing) procedures (*1) to date, has conducted microdeletion and microduplication syndrome screening for 4,543 individuals (*2).

Out of these 4,543 individuals, 1 person received a definitive positive screening result for DiGeorge syndrome, which was subsequently confirmed as a true positive via invasive diagnostic testing. Additionally, among 5 individuals whose results were initially classified as uninformative (inconclusive), 2 underwent amniocentesis; consequently, 1 case of 22q11.2 duplication and 1 case of Emanuel syndrome were detected. The case diagnosed as Emanuel syndrome returned an amniocentesis karyotype of 47,XY,+der(22)t(11;22)(q23.3;q11.2), an abnormality involving a reciprocal translocation between position q23.3 on chromosome 11 and position q11.2 on chromosome 22. Although the targeted DiGeorge screening is designed to detect microdeletions at the 22q11.2 locus, the chromosomal displacement at this exact site triggered an abnormal flag. This demonstrates that Hiro Clinic’s NIPT screening can detect structural variations related to duplications and translocations, not just microdeletions. No follow-up reports were received for the remaining 3 uninformative cases. Furthermore, out of 5 cases classified as highly likely to be positive (borderline results), 2 were subsequently confirmed negative via amniocentesis, while the remaining 3 did not undergo amniocentesis.

DiGeorge syndrome is a condition caused by a microdeletion on chromosome 22, with an estimated prevalence of approximately 1 in 4,000 to 6,000 individuals in the general population. Through microdeletion and microduplication screening, aberrations localized within the same targeted chromosomal regions may also be discovered. Thus far, at least 3 out of 4,543 individuals have had deletions or duplications in the 22q11.2 region confirmed via invasive diagnostic testing. The following table will be updated as soon as follow-up data from individuals who have not yet undergone invasive testing becomes available.

ディ・ジョージ症候群の概要と症状

ディ・ジョージ症候群は、特定の遺伝子の欠損によって引き起こされる遺伝疾患です。この症候群は胸腺や副甲状腺の低形成、先天性心血管系の異常、特徴的な顔貌など多様な症状を引き起こす可能性があります。また、免疫系の問題や反復する感染症、粘膜下口蓋裂による発話困難などが特徴的です。

エマヌエル症候群の概要と症状

染色体の一部が他の染色体と入れ替わる現象を転座染色体と呼びます。この現象により、転座保因者は子どもを持つ際に流産や不妊のリスクがあります。特に11番と22番の染色体の転座から、エマヌエル症候群が生じることがあります。この症候群は特定の遺伝子検査により診断され、生まれつきの心疾患や、口蓋裂、鎖肛や腎臓の奇形など重篤な染色体異常が引き起こされます。

22q11.2 微細重複症候群の概要と症状

22番染色体の一部が重複することで発生し、80%の患者に先天性心疾患などが見られます。特にファロー四徴症が代表的で、心室中隔欠損や大動脈騎乗などが含まれます。心血管疾患は生命予後に大きく影響し、その他多様な臨床症状も見られます。

7つの微小欠失・重複疾患の欠損部位

7つの微小欠失・重複疾患は、「22番染色体の長腕」、「1番染色体短腕」、「17番染色体短腕」、「4番染色体短腕」、「5番染色体短腕」、「15番染色体長腕」の微細な領域に欠損があるために生じる疾患です。
下の罹患部位に書いてある一番最初の数字が染色体の番号であり、そのあとの「ｐ」が短腕、「ｑ」が長腕を指します。短腕は染色体の上の部分、長腕は染色体の下の部分を指します。その次の番号は中央のセントロメアから数えて何番目の領域かを示しており、「-（マイナス）」はその部位が欠失していることを指しています。

もし、陽性であったなら羊水検査を推奨します

検査結果が陽性になった場合、当院では羊水検査を強く推奨いたします。羊水穿刺後、羊水はマイクロアレイまたはエクソーム解析にかける必要があります。
この検査を行っている国内の検査所は少ないのが実情です。解析にかけ、状態を確認したいという受検者様は当院にご相談ください。検査所をご紹介いたします。