這個病例是：前腦無裂序列征（Holoprosencephaly Sequence），（無嗅腦-猴頭畸形-獨眼：脊索前中胚層原發(fā)異常）。非常典型。

相關(guān)資料參考如下：

前腦不能正常分裂形成兩側(cè)大腦半球，導(dǎo)致側(cè)腦室和第三腦室融合，顏面和腦組織結(jié)構(gòu)及功能缺陷。發(fā)病率約為胚胎中1:250，出生嬰兒1:5000～10000。性別比：男:女=1:3（無分葉型）；男:女=1:1（分葉型）。病因見本文后面所述。非染色體異常所致的全前腦多為散發(fā)性，其再發(fā)生風(fēng)險率約6%。

在胚胎發(fā)育的第3周，脊索前中胚層向脊索前方移行是形態(tài)學(xué)上發(fā)生前臉或前腦的必要步驟。脊索前中胚層異?？蓪?dǎo)致不同程度的臉中線發(fā)育異常，尤其是中線鼻發(fā)育（切牙骨）和前腦的形態(tài)發(fā)育不全。

前腦無裂畸形者大腦皮質(zhì)發(fā)育差而常出現(xiàn)小頭，但有腦積水時頭可增大。由于大腦半球分不開，可形成一系列不同程度的面部中線結(jié)構(gòu)畸形。

（一）獨眼是早期臉中線發(fā)育嚴(yán)重異常的表現(xiàn)。眼融合，嗅覺基板融合成為管狀象鼻樣結(jié)構(gòu)，位于眼的上方，篩骨等其他中線結(jié)構(gòu)缺如。獨眼畸形中，前腦分裂失敗形成形態(tài)學(xué)上不完全的前腦。

（二）在畸形較輕的病例中，可表現(xiàn)為眼距過近和不同程度的中臉或前腦發(fā)育不全，通常含有唇、腭裂。

（三）中線器官發(fā)育不全，如器官距離過近、人中或鼻中隔缺如、單一中心門齒、先天性鼻梨形孔狹窄、上唇系帶缺如等，提示存在嚴(yán)重腦發(fā)育不良或功能異常。

（四）根據(jù)大腦半球的分開程度，前腦無裂畸形有以下3種類型：

1）無葉全前腦：最嚴(yán)重，大腦半球完全融合未分開，大腦鐮及半球裂隙缺失，僅單個原始腦室，丘腦融合成一個。

2）半葉全前腦：為一種中間類型，介于無葉全前腦和葉狀全前腦之間。顳葉及枕葉有更多的大腦組織，大腦半球及側(cè)腦室僅在后側(cè)分開，前方仍相連，仍為單一側(cè)腦室，丘腦常融合或不完全融合。

3）葉狀全前腦：大腦半球及腦室均完全分開，大腦半球的前后裂隙發(fā)育尚好，丘腦亦分為左右各一，但仍有一定程度的結(jié)構(gòu)融合，如透明隔消失。

無葉全前腦可根據(jù)單一側(cè)腦室、丘腦融合、腦中線結(jié)構(gòu)消失及長鼻、眼距過近或獨眼等做出診斷。有報道經(jīng)陰道超聲在14孕周前可做出診斷。

半葉全前腦如能仔細(xì)檢查，仔細(xì)辨認(rèn)腦內(nèi)結(jié)構(gòu)和面部畸形，可于產(chǎn)前做出診斷。

葉狀全前腦由于腦內(nèi)結(jié)構(gòu)異常及面部結(jié)構(gòu)異常不明顯，胎兒期很難被檢出。

無葉全前腦

1）腦內(nèi)結(jié)構(gòu)紊亂：正常結(jié)構(gòu)如側(cè)腦室、丘腦，不能很好分辨，不能顯示兩個側(cè)腦室、兩側(cè)丘腦，僅可見一個較大的原始腦室，中央見單一丘腦回聲結(jié)構(gòu)，呈融合狀。腦中線結(jié)構(gòu)消失，如腦中線回聲消失，透明隔腔及第三腦室消失。胼胝體消失，腦組織變薄。

2）面部結(jié)構(gòu)嚴(yán)重異常：可出現(xiàn)長鼻畸形或象鼻畸形，單眼眶或眼眶缺失，單眼球，中央唇裂。

3）早孕期表現(xiàn)：早孕期不能顯示大腦鐮，胎頭呈“氣球樣”。

半葉全前腦

1）前部為單一腦室腔且明顯增大，后部可分開為兩個腦室，丘腦融合，枕后葉部分形成。

2）顱后窩內(nèi)囊性腫物，多為增大的第四腦室或顱后窩池。

3）可合并Dandy-Walker畸形。

4）眼眶及眼距可正常，扁平鼻。也可合并有嚴(yán)重面部畸形，如猴頭畸形、單鼻孔畸形等。

葉狀全前腦

1）胎兒期超聲診斷困難，不易識別。

2）透明隔腔消失時應(yīng)想到本病可能，可伴有胼胝體發(fā)育不全，冠狀切面上側(cè)腦室前角可在中線處相互連通。

3）面部結(jié)構(gòu)一般正常。

多數(shù)病例均為散發(fā)，原因不明。

現(xiàn)認(rèn)為前腦無裂畸形是遺傳與環(huán)境多因素綜合作用的結(jié)果。

嚴(yán)重的染色體結(jié)構(gòu)異常包括del 2p21、dup 3pter、del 7q36、del 13q、de1 18p和del 21q22.3均需考慮可能為本病的病因。

此外，一些導(dǎo)致本病相關(guān)的突變基因已得到證實，如一些常染色體顯性遺傳畸形中，最多見的是7q36位點的Shh基因突變的結(jié)果。其他基因如位于13q32的ZIC2、2q21的SIX3和18pl1.3的tgif等基因突變與散發(fā)及家族病例有關(guān)。其他一些與腦發(fā)育相關(guān)的重要信號傳導(dǎo)通路基因如PATCHED1(ptch)和GLI2，與Shh信號及與轉(zhuǎn)化生長因子(TGF-β)通路有關(guān)的TDGF1和FAST1突變，也與本病有關(guān)。

應(yīng)檢查患兒的父母是否存在單一門齒、上唇系帶缺如和鼻軟骨缺如。

此外，患糖尿病的母親或患Meckel-Gruber綜合征的女患者可能生育前腦無裂的胎兒。

前腦無裂畸形可見于如下綜合征：

13三體綜合征、18三體綜合征、l8p缺失綜合征、1lq缺失綜合征、13q缺失綜合征、22q 11.2缺失綜合征、缺指（趾）-外胚層發(fā)育不良-唇楞裂綜合征、胎兒乙內(nèi)酰脲綜合征、同卵雙生及結(jié)構(gòu)畸形、Pallister-Hall綜合征、Smith-Lemli-Opitz綜合征、三倍體綜合征。

（點擊上圖可以放大查看）

無葉全前腦和半葉全前腦常為致死性的，出生后不久即夭折。而葉狀全前腦可存活，但常伴有腦發(fā)育遲緩，智力低下。

由于此類畸形患者的中樞神經(jīng)系統(tǒng)功能預(yù)后很差，建議對確診為嚴(yán)重前腦發(fā)育異常的存活者慎用超出常規(guī)的支持治療。

檢索文獻：

Cyclopia，Holoprosencephaly，Holoprosencephaly Sequence

Cyclopia

This article is about the congenital disorder. For other uses, see Cyclopia (disambiguation).

Cyclopia (also cyclocephaly or synophthalmia) is a rare form of holoprosencephaly and is a congenital disorder (birth defect) characterized by the failure of the embryonic prosencephalon to properly divide the orbits of the eye into two cavities. Its incidence is 1 in 16,000 in born animals and 1 in 200 in miscarried fetuses.[1][2]

Presentation

Typically, the nose is either missing or replaced with a non-functioning nose in the form of a proboscis. Such a proboscis generally appears above the central eye, or on the back, and is characteristic of a form of cyclopia called rhinencephaly orrhinocephaly.[3] Most such embryos are either naturally aborted or are stillborn upon delivery.

Although cyclopia is rare, several cyclopic human babies are preserved in medical museums (e.g. The Vrolik Museum, Amsterdam).[4]

Some extreme cases of cyclopia have been documented in farm animals (horses, sheep, pigs, and sometimes chickens). In such cases, the nose and mouth fail to form, or the nose grows from the roof of the mouth obstructing airflow, resulting in suffocation shortly after birth.[5]

Causes

Genetic defects or toxins can misdirect the embryonic forebrain-dividing process.[6] One highly teratogenic alkaloid toxin that can cause cyclopia is cyclopamine or 2-deoxyjervine, found in the plant Veratrum californicum (also known as corn lily or false hellebore). Grazing animals are most likely to ingest this plant and induce cyclopia in offspring. The mistake of humans ingesting Veratrum californicum while pregnant is often due to hellebore, an unrelated plant with the same name, being recommended as a "natural" treatment for vomiting, cramps, and poor circulation, three conditions which may be present in the early stages of pregnancy. [7] Cyclopia occurs when certain proteins are inappropriately expressed,[8] causing the brain to stay whole, rather than developing two distinct hemispheres. This leads to the fetus having one optic lobe and one olfactory lobe, resulting in the eye and nose malformations of cyclopia.[9]

The sonic hedgehog (SHH) gene regulator is involved in the separation of the single eye field into two bilateral fields. Although not proven, it is thought that SHH emitted from the prechordal plate suppresses Pax6, which causes the eye field to divide into two. If the SHH gene is mutated, the result is cyclopia, a single eye in the center of the face (Gilbert, 2000).

Notable cases

§  A British description from 1665 of a colt apparently suffering from cyclopia reads:

First, That it had no sign of any Nose in the usual place, nor had it any, in any other place of the Head, unless the double Bagg CC that grew out of the midst of the forehead, were some rudiment of it. Next, That the two Eyes were united into one Double Eye which was placed just in the middle of the Brow.[10]

§  On 1 March 1793 a 46-year-old woman in Boalts Torp, Glim?kra, Sweden gave birth to a child with cyclopia that died after 2 hours. The child was 35 cm long, its face without nose and nostrils, the lidless eye with no eyebrow sat raised on the middle of the forehead like a large blueberry. The wrists were somewhat crooked as well as the right foot which was completely crooked and bent inwards. It was not clear whether it was a boy or a girl but it was believed to be the former.[11]

A Swedish description from 1793 of a newborn with cyclopia

§  On December 28, 2005, a kitten with cyclopia, "Cy", was born in Redmond, Oregon,United States and died about one day after birth.[12]

§  In 2006, a baby girl in India with cyclopia was born. Her only eye was in the center of her forehead. She did not have a nose and her brain was fused into a single hemisphere.[13]The child died one day after her birth.[14]

§  In 2011 a cyclops shark fetus was discovered in the body of a caught shark in Mexico, with no discernible nose and one giant eye. The unborn fetus was turned over for medical studies.[15]

§  On October 10, 2012, a small kitten was born. Its eye was in the center of the forehead and there was no developed nose to be found. The small cat died shortly after it was born. It was nicknamed Cleyed the Cyclops.[16]