염색체질환 Chromosome Diseases (II)



  • Imbalances concerning gonosomes are less deleterious than those affecting autosomes; Imbalances leading to an excess of gene dosage (i.e. duplications, trisomies) are less deleterious than those resulting in a deficit (i.e. deletions, monosomies).

  • Bias of sampling: the most deleterious chromosome imbalances are not seen but result in early miscarriages; miscarriages and stillbirths occur in other syndromes, and only the less deleterious are compatible with life.

  • Some signs are characteristic of the disease. They are due to a gene effect or to the combination of genes effects. their association can be called a contiguous gene syndrome (see below).
    Other signs are aspecific of the region involved; they are the result of general gene imbalance and/or cell division disturbances, and may be found in many chromosome syndromes: growth retardation, microcephaly, mental retardation, low set ears ... can be found in various disease with no gene similarity.

  • Type/contertype: trisomy 4p syndrome (not herein described) exhibit some signs which are the opposite of del(4p) syndrome (e.g. flat/high forehead, aplasic/large glabella, prognatism/microretrognatism). In trisomy 4p, genes located in 4p are in 3 sets, while in del(4p) these genes are in only 1 set. This is an example of probable gene dosage specific effects.

  • Haploinsufficiency: is a term used in case of a deleted segment with deleterious effects; it means that the remaining haploid set of gene(s) is insufficient to allow a normal function.

  • Critical region: it was previously thought that a trisomy phenotype was due to the global excess of the extra chromosome (e.g. trisomy 21), and a deletion syndrome to the haploinsufficiency of the whole deleted segment. With the description of cases with overlapping imbalances, it became clear that some regions of imbalance had more deleterious effects, while others induced only mild disturbances. The critical segment is, in some instances, very narrow: band q22.3 is responsible of most of the trisomy 21 phenotype; it may even be smaller: the 200 kb critical segment in del(4p) syndrome. In the latter case, one has even evoked the notion of "continuous genes syndrome".

  • Continuous genes syndrome: some Mendelian inherited diseases have been known for long, and their deleterious effect well described. It has happen that a given patient had presented with the addition of phenotypes from different inherited diseases. A well known example is that of a patient with the addition of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and Mc Leod syndrome. This patient had a deletion in Xp21, where all these genes map.

  • Cryptic rearrangements/imbalances: it is likely that a percentage of chromosome imbalances remain undetected and/or undetectable: some of these imbalances are probably cause of major anomalies; the location of the chromosome imbalance may not be suspected if the phenotype is not reminiscent of a well known syndrome; others cryptic imbalances may have no, or slight effects, and will never be uncovered (another bias of sampling!). 

상염색체 질환

1) DELETION 4p (Wolf-Hirschhorn syndrome / Pitt-Rogers-Dank syndrome)

  • 핵형 : del(4)(p16)
  • 임상 :
    • 경하성(hypotrophy), 저체중(low birth weight: 2 kg).
    • 소두증(microcephaly), high forehead, large glabella, broad nose in prolongation of the eyebrows line: greek helmet aspect.
    • 양안격리증(hypertelorism), 안기형(ocular malformations), 구순 및 구개열(hare-lip/cleft palate).
    • long, slender, manicured fingers.
  • 기형 :
    • 심장 (50%).
    • 안(眼); 특히 colobomata (25%).
  • IQ = 20; seizures; often bedridden.

2) DELETION 5p (cri-du-chat syndrome)

  • Cri du Chat 증후군은 5번 염색체 단완 일부의 소실 또는 이동에 따른 유전적 질환으로 1963년 Down 증후군의 원인을 밝힌 Lejeune 교수에 의해 처음 확인됨.
  • Cri du Chat는 불란스어로 "고양이 울음소리"란 뜻임.
  • 핵형 : 가장 흔한 결실부위는 5p14-15인데, 중요한 절편은 약 2Mb 길이를 가진 5p15.2 부위이다. 환자 85%는 원발성(de novo)이고 15%는 부모가 균형전좌형을 가진 가족성(familial)이다.
  • 역학 : 출생아 1000명당 0.02명의 환자
  • 임상 :
    • 신생아기에 전형적인 고음의 고양이 울음소리를 내고 일과성.
    • 소두증(microcephaly), 원형안모(round moon-shaped face), 양안격리(hypertelorism), 넓은 비교(broad nasal bridge), 안검열경사(downward slanting palpebral fissures), 소악증(micrognathia), 성장지연(growth retardation)
    • triradius axial in t'.
    • 신생아기에서의 저긴장증(hypotonia)
    • 성인에서는 과반응(hyperactivity), tantrums, 파괴적 행동(destructive behaviour)이 흔하고, 자폐증과 유사한 임상소견을 보일 수 있음.
    • IQ가 20 정도인 심한 정신운동 지체증(heavy psychomotor retardation)
  • 신체기형(Malformations)은 드문 편임.


  • Epidemiology: sex ratio 3M/1F; increased parental mean age.
  • Clinics:
    • high forehead, everted lower lip.
    • discrete dysmorphia.
    • dermatoglyphics: deep palmar/plantar furrows.
  • Malformations: kyphoscoliosis, hemivertebrae and other osteoarticular disorders.
  • I Q: 50 to 70 mainly; however, cases with normal intelligence and no visible malformation remain undetected.

  4) TRISOMY 9p

  • Karyotype: critical segment likely to be in 9p22-p24.
  • Clinics: microcephaly, deeply set eyes, broad nose.
  • Malformations: rare.
  • I Q = 50.

5) TRISOMY 13 (Patau syndrome)

  • I. Epidemiology:
    • 0.1 / 1 000 births.
    • increased parental age.
    • normal pregnancy duration.
    • life expectancy: frequently found in early miscarriages, and in late miscarriages; stillbirths are common, and babies often die in the neonatal period; very few reach adulthood.

  • II. Clinics:
    • microcephaly, receding forehead.
    • microphtalmia/anophtalmia, colobomata of the iris, cataract.
    • arrhinencephaly, probocis.
    • hypotelorism.
    • scalp defect (in relation with neural tube fusion defects).
    • hare-lip / cleft palate.
    • umbilical hernia: 1/3 of cases.
    • genitalia: cryptorchidy in the male, uterus bicornis (constant) and vagina duplex (often) in the female.
    • fingers in flexion position; postaxial polydactyly 80 % (hands and feet); club foot; dermatoglyphics: axial triradius in t"; thenar pattern.

  • III. Malformations: constant, heavy, leading to early death in most of the cases.
    • Central nervous system :
      • arhinencephaly (50 %).
      • hypoplasia of the corpus callosum (20 %).
      • hypoplasia of the frontal lobe.
      • spina bifida.
    • Ocular:
      • micro/anophtalmia (90 %).
      • coloboma.
      • retinal dysplasia.
      • luxation or absence of lens.
    • Cardiac (constant):
      • ventricular septal defect.
      • patent foramen ovale.
      • persistence of ductus arteriosus
      • tetralogy of Fallot.
    • Renal (50 %):
      • hydronephrosis.
      • polykystic kidneys ...
    • Digestive (50 %):
      • malrotation of the intestine.
      • malformation of the pancreas.
      • gallbladder agenesis.
    • Bones:
      • spina bifida.
      • rib malformations.

  • IV. Karyotype:
    • most often free and homogenous trisomy.
    • sometimes translocation t(13q;14q).
    • sometimes mosaic trisomy.

  6) DELETION 18p (Edwards syndrome)

  • brachycephaly, ptosis, broad nose, irregular teeth.
  • kyphoscoliosis.
  • holoprosencephaly (10%).
  • IQ = 50; may have psychiatric behaviour.

  7) DELETION 18q

  • Karyotype: deletion of 18q21-qter most often; critical segment maps to 18q23.
  • Clinics:
    • severe hypotonia (frog-like).
    • midface hypoplasia; carp-shaped mouth.
    • tapered fingers.
    • hearing impairment
    • growth retardation
  • Malformations:
    • ocular: constant.
    • osteoarticular.
    • genitalia.
    • variable IQ, from 30 to over 70.


 8) TRISOMY 18

  • I. Epidemiology:
    • 0.2 / 1 000 births.
    • increased parental age.
    • pregnancy duration is often prolonged.
    • life expectancy: frequently found in miscarriages; stillbirths are common, and babies often die in the neonatal period; very few reach adulthood.

  • II. Clinics:
    • hydramnios; single umbilical artery frequently.
    • low birth weight: 2,3 kg.
    • constant sign: hypoplasia of the first branchial arch, which implicates:
        --> low set ears
        --> microretrognatism
    • Pierre Robin syndrome:
      • microretrognathism,
      • cleft palate,
      • glossoptosis.
    • microcephaly (40 %), dolichocephaly.
    • short neck with excess of skin .
    • Faun-like ear.
    • short thorax and sternum, making the abdomen looking long.
    • hernias: diaphragmatic, umbilical, inguinal.
    • cryptorchidism (30 %).
    • clubfoot; irreducible flexion of forearms; dysplastic nails, absence of distal flexion crease of fingers; clenched fingers with overlap of the 2nd and 5th onto the 3rd and 4th; dermatoglyphics: frequency of arches.

  • III. Malformations: constant, heavy, leading to early death in most of the cases.
    • Cardiac: constant.
      • ventricular septal defect.
      • patent foramen ovale.
      • persistence of ductus arteriosus
      • valves anomaly, in particular mitral valve
    • Renal (1/3): mostly horseshoe kidney, hydronephrosis, polykystic kidneys, hyploplastic kidneys.
    • Digestive: frequent; Meckel, anal atresia; pancreas anomalies.
    • Brain
    • Bones: spina bifida, hemivertebrae , absence of clavicle.

  • IV. Karyotype:
    • most often free and homogenous trisomy.
    • frequency of doubles aneuploidies and mosaics.

묘안증후군(cat eye syndrome)

    1. 묘안 증후군(猫眼症候群)이란?

    묘안 증후군은 정신박약, 홍채결손, 항문폐쇄, 이개전누공, 선천성 심질환, 요로계 기형, 골격계 기형 등을 동반하는 증후군으로 이 증후군의 환자는 소수의 경우에 어린 시절 여러 가지 기능 이상으로 인하여 사망하기도 하지만, 그 외에는 특별한 이상이 없는 한 수명이 심각할 정도로 단축되거나 하지는 않는 것으로 알려져 있다. 이 증후군의 정신지체 정도는 환자에 따라 정상 수준에서 심한 지체를 보이는 경우까지 매우 다양하게 나타난다. 묘안 증후군의 발병빈도는 대략 50,000∼150,000명당 1명이라고 알려져 있다.

    2. 원인과 유전양상

    묘안증후군은 희귀한 질환이며, 22번 염색체의 이상에 의해 야기되는 것으로 알려져 있다. 즉, 22번 염색체의 단완(short arm)에서 장완(long arm)의 일부(22pter-->q11)까지가 정상인의 경우에는 2개만 존재하는 반면에 이 환자에서는 3개(trisomic) 또는 4개(tetrasomic)가 존재함으로써 이러한 유전자양의 변화가 환자에서 나타나는 여러 가지 증상을 유발하는 것으로 알려져 있다.

    3. 진단과 치료

    묘안증후군은 홍채결손증과 항문폐쇄증과 심장 및 신장의 이상과 같은 특이적 증상으로 진단을 하거나 최근에는 분자유전학적 진단방법으로 FISH(fluorescence in situ hybridization)조사방법을 사용한다. 묘안증후군의 완전한 치료법은 아직 알려지지 않았으나, 각 증상별로 치료가 필요하다. 항문폐쇄와 복합적인 심장이상에 대하여 외과적 수술이 필요하다. 또한 소장의 이상도 고려되어야 하며, 짧은 신장을 가진 환자에게는 성장호르몬을 통한 치료를 고려할 수도 있을것이다.

    4. 최근연구

    최근에는 묘안증후군의 이상을 유발하는 22번 염색체에서 중복부위를 분석하고 중복이 일어나는 부분(breakpoints)을 구분하여 각 부분의 크기 및 그에 따라 묘안증후군을 분류하고, 표현형의 차이를 분석하는 연구들이 이루어지고 있다.

    5. 관련 사이트



In a few words, Turner syndrome (or Ullrich-Turner syndrome) is a syndrome of growth retardation and impuberism with frequent cardiovascular or renal malformation, normal intelligence, due to a chromosome imbalance: 45, X and variants.

  • I. Epidemiology:
    • 0.4 /1000 female births (but 20 % of chromosome anomalies found in early miscarriages, i.e. about 10% early miscarriages).
    • due to the loss of the maternal gonosome (a X) in 20-30% of cases, or of the paternal gonosome (a X or a Y) in the remaining 70-80%.

  • II. Clinical ascertainment/examination:
    The diagnosis can be evoked either:
    • in the newborn (from dysmorphia and/or malformations), or:
    • in the girl (from growth retardation, impuberism).

    1 - neo-natal form:

    • prenatal (and postnatal) growth retardation
    • single umbilical artery frequently.
    • Bonnevie-Ullrich (BU) status associating:
      • lymphoedema of hands and feet (tough, non inflammatory, regressive at age 2 yrs).
      • excess of skin and webbed skin on the nucha (pterygium colli). 1/3 of BU are found in Turner syndrome, and 75 % of Turner have a BU In the presence of this symptomatology, a karyotype will be undertaken and (cardiac, renal) malformations will be searched for.

    2 - in childhood or adolescence:

    • small size (adult < 1,45 m).
    • triangular shaped face, looks sad.

    • hypertelorism.
    • blepharoptosis.
    • possible epicanthus.
    • downward slanting palpebrale fissures.

    • short neck.
    • pterygium colli in more than half cases.
    • low hair line.
    • high-arched palate.
    • micrognatism.
    • low set hears

    • shield chest.
    • widely spaced nipples.

    • short 4th metacarpal.
    • cubitus valgus (increased carrying angle of the elbow).
    • radius curvus (Madelung's deformity).
    • sinking of internal tibial plateau (sign of Kosowizc in the adult).
    • osteoporosis (and fracture increased risk) above 45 yrs.

    • multiple pigmented nevi; vitiligo and/or café-au-lait spots.
    • risk of keloid scars (surgery only when needed, avoid plastic surgery).

    • dermatoglyphics: number of digital crests = 187 - (30 * X) - (12 * Y) (herein = 157).
    • hypoplastic nails

    • infantile external genitalia.
    • hypoplastic uterus.
    • amenorrhea and sterility.
    • absence of breast development.
    • rare pubic pilosity.

    • normal or subnormal intelligence; the (slight) cognitive defects are limited to visual-spatial/perceptual abilities, attention, motor function, and nonverbal memory. May be partly due to psycho-social suffering, but also to genetic imbalances and their various consequences (e.g. hormone deficiency).
    • cardiovascular (20-30%): aortic coarctation (10-15 %) which may lead to death by dissection or rupture of the aorta; bicuspid aortic valve; left superior vena cava, and other malformations; in the presence of aortic coarctation in a girl, a Turner syndrome must be evoked.
    • renal (40-50 %): horseshoe kidney, hydronephrosis...
    • congenitally dislocated hip, scoliosis
    • sense-organs: deafness (impaired hearing in up to 40%), myopia, cataract, strabismus.
    • X linked recessive inherited traits have the same frequency in Turner syndrome and in the male, since they both have only 1 X; this frequency is that of the allele (e.g. daltonism, hemophilia, Duchenne de Boulogne myopathy...).

  • III. Diagnosis: the karyotype:
    • 45, X homogeneous: 55 % of cases.
    • isochromosomes: i(Xp), i(Xq); deleted chromosomes: del (Xp), del (Xq); rings: r(x); mosaicisms... --> phenotypes are more or less evocative of Turner syndrome some patients having been fertile.
    • most of the phenotypic traits are due to Xp deletion, and only ovarian failure is consistently associated with Xq deletions.

  • IV. Assessments:
    • ovarian failure (sex steroid deficiency and amenorrhea).
    • streak gonads (germinal cells regress at the 3rd month in utero; biopsy is not needed).
    • impaired glucose tolerance; hypertension (20-30%).
    • autoimmune thyroid disease (T4, TSH, thyroid-antibody titer determinations).
    • X-rays (skeleton, urinary system, heart).

  • V- Differential diagnosis:
    • other disorders with Bonnevie-Ullrich status.
    • gonadic dysgenesia.
    • other disorders with primary amenorrhea; e. g.: XY females (sex reversal).

  • VI. Treatments:
    • surgery of malformations.
    • gonadectomy if a Y chromosome is present in mosaic (neoplastic risk).
    • growth hormone and oestrogens to manage growth failure and to induce menarch and secondary sexual characters and menarche and to prevent osteoporosis.
    • psychological support (sterility).

    Comments: Genes implicated in the syndrome are thought to be localised in the region of the gonososomes which escape X inactivation; the various clinical manifestations may either be due to haploinsufficiency of specific genes (in the pseudoautosomal region of X), aneuploidy effects (e.g. on meiosis), and/or fetal suffering from the lymphoedema.


In a few words, Klinefelter syndrome is a syndrome of a normal or gynecoid male with normal intelligence or mild retardation, infertility, and possible behaviour or psychiatric problems, due to a chromosome imbalance: 47, XXY and variants.

  • I. Epidemiology:
    • 1.5 /1 000 male births.
    • increased maternal age.
    • the extra X comes more often from the mother.

  • II. Clinical ascertainment/examination:
    • wide variability in clinical expression:
    • rarely diagnosed in childhood (from mental retardation or non specific anomalies of genitalia),
    • more often at puberty (from gynecomastia, small testes),
    • or when consulting for infertility.

    • physical aspect is often normal,
    • they may present with tallness and macroskelia,
    • or with gynecoidy (gynecoid obesity: 25 %; gynecomastia: 15-25 %; bi-trochanteric diameter > bi-acromial diameter).
      • normal penis.
      • small, indolent testes.
      • normal or rare, feminine shaped pubic pilosity.
      • libido diminished; impotence at age 30 yrs is frequent.
      • sterility.
      • normal or moderately delayed intellectual development.
      • dyslexia/dysphasia and frontal-executive dysfunction.
      • psychiatric behaviour is not rare.
    • 50-fold increased risk of developing breast cancer as compared to normal males (and 8 times less than in females, as the women’s risk is 400 times that of men) (nearly 10% of breast cancers in males are found in Klinelter patients).

  • III. Diagnosis: the karyotype:
    • 47 XXY homogeneous: 80 % of cases.
    • XXXY, XXXXY, XXYY: 10 %.
    • in mosaic: 5-10 % (may (rarely) be fertile).

  • IV. Assessments:
    • high gonadotropins and low testosterone plasma levels.
    • azoospermia in most non-mosaic cases; however, intratesticular residual foci of spermatogenesis may occasionally be found, and mature spermatozoa may permit paternity using intracytoplasmic sperm injection.
    • biopsy (not needed): seminiferous tubes atrophia, Leydig hyperplasia .

    Treatment: testosterone replacement therapy to correct the androgen deficiency and to provide virilization; can also has positive effects on mood and self-esteem.

  3) FRAXA and FRAXE SYNDROMES (Fragile Xq or fra(X)(q28))

  • I. Epidemiology:
    • FRAXA: 0.2 / 1 000 male births and 0.1 / 1 000 female births.
    • FRAXE: 0.02/ 1 000 male births.

  • II. Clinics:
    • the face reminds of the one found in trisomy 8.
    • macrocephaly.
    • high forehead.
    • midface hypoplasia.
    • large nasal root.
    • prognathism.
    • thick lips.
    • high palate.
    • large, unfolded ears.
    • macroorchidy.
    • fertility is often normal.

  • III. Mental development and psychiatric behaviour (paragraph written by Denis Reserbat-Plantey):
    • In the male:
      • Mental retardation is mild to severe (mean IQ = 50): from a delay in school training to the impossibility to acquire writing and reading skills. The Fragile Xq young child is often hypotonic; in the more severe forms, a psychomotor delay is already present (delay in walking...).
      • Speech difficulties: delay language appearance, dysarthria, omissions, mumblings, echolalias (tendency to repeat the same sentences and to ask the same questions).
      • Behaviour problems: anguish, attention deficit, hyperactivity, impulsiveness, escape of glance, resistance to change, aggressiveness, self-mutilation, stereotypies (wings beating, "flapping") and oddities. Sometimes all these symptoms are present, and constitute an autistic syndrome.
      • The various studies carried out among the autists show that 5 to 7 % autists are Fragile Xq.
    • In the female:
        The mental retardation is mild or absent. They can present with: school difficulties (less than in the boy), memory disorders, changing mood, timidity, relational difficulties, and depressive tendency. These symptoms are often misinterpreted for social causes.

  • IV. Diagnosis: the karyotype can show recurrent gaps in Xq27-q28; however, the diagnosis now rely on the molecular study of the genes.


  • The disease is due to the hyperexpansion of a CGG trinucleotide repeats in the 5' untranslated region of the gene FMR-1 (fragility, mental retardation), located in Xq27.3.
  • As a consequence of their hyperexpansion, these CpG islands become hypermethylated, leading to shut down the FMR-1 gene expression.
  • The normal FMR-1 product is a protein called FMRP, a RNA binding protein widely expressed, in particular in the brain and the testis
  • In the normal population, the CGG repeat size is variable, from 6 to 54 repeats; it is inherited in a stable manner.
  • Some people have between 60 and 200 repeats; this is called premutation; it is inherited in an unstable manner (you tend to have more repeats than Mummy), but stable in the individual (identical in each cell). Premutation carriers have a normal phenotype. Frequency of premutations in the population is 2.5/1000.
  • Hyperexpansion of more than 200 repeats are called full mutation; they are hypermethylated (on cytosines; even on the active X); it is inherited in an unstable manner, but also, the mutation is unstable in the individual (somatic mutations). Almost all males and half of females with the full mutation exhibit the syndrome. It is milder in females.


  • passage from the normal allele to premutation as never been observed.
  • passage from premutation to mutation (unstability, or expansion through inheritance) is only through transmission from a female carrier.


  • locus in Xq27-q28, 600kb distal to FRAXA.
  • Identical process of hyperexpansion of CpG islands.
  • much milder phenotype.

    Note: this type of unstable mutations has been found in other diseases, such as Huntington disease, a progressive neuropsychiatric disorder with CAG repeats in 4p16.


 4) 47,XXX

  • 역학: 1 / 1 000 여자 출생아; 부모 노령화에 따른 빈도 증가.
  • 임상:
    • 발견되지 않는 경우가 많음. 정상 표현형, 사춘기, 임신, 출산을 보이는 정상 여자
    • 폐경기가 일찍 끝나는 경우가 많고(precocious menopause).
    • 경증의 정신지체 및 간혹 사회적응력에 약간의 문제점이 있을 수 있음

 5) 48,XXXX and 49, XXXXX

  • 21번 염색체 삼체성(trisomy 21)과 매우 비슷하고, 정신박약(mental retardation).

 6) 47,XYY

  • Epidemiology: 1 / 1 000 male births.
  • Clinics:
    • often undetected: a normal but tall male with a normal phenotype.
    • fertility may be reduced; normal offspring.
    • mild mental delay can be present; impulsivity,violence, and psychiatric behaviour are not rare.


  • Epidemiology: 0.1 / 1 000 male births.
  • Clinics: Klinefelter like phenotype; sterility.
  • Sex reversal can be due to the presence of male determining sequences on a X chromosome (from a X/Y interchange at paternal meiosis), or on an autosome (from a Y/autosome translocation in the father), in particular SRY (Sex determining Region, Y chromosome). Other sex determining genes, usually sitting on gonosomes or on autosomes are likely to be involved.


  • Epidemiology: 0.1 / 1 000 female births.
  • The phenotype is that of a female with ovarian failure, and with or without other stigmata (e.g. sexual anomalies, limbs anomalies).
  • Sex reversal in XY females can be due to mutations in SRY in 15%, or to other known or unknown genes mutations; some of these genes map to autosomes (e.g. SOX9 on chromosome 17).


누난증후군은 출생 후의 성장지연으로 키가 작고, 목이 짧은 익상경, 움푹 파인 가슴뼈(함몰흉), 폐동맥협착증, 잠복고환 등의 특징을 가지는 다인성 질환이다. 1968년 J. A. Noonan에 의해 폐동맥협착증을 가진 17명의 환자를 포함한 19명의 환자를 소개하면서 누난증후군으로 명명되었다. 그 중 12명은 남자, 7명은 여자였다. 이 증후군은 또한 익상경 증후군이라고도 불렀는데, 이는 누난증후군의 많은 소견 중에 하나에만 집중된 용어이다. 다른 이름으로는 남성 터너증후군, 여성 가성 터너증후군, 터너 형질, 터너유사증후군 등이 있으며, 이러한 용어들은 터너증후군에서 나타나는 작은 키와 익상경(목이 물갈퀴 모양)이 누난증후군과 유사하므로 붙여진 이름이다.

터너증후군은 X 염색체가 하나 없는 염색체이상 질환으로 여성에게만 나타나는 질환이다. 누난증후군과 터너증후군 환자들의 유사한 표현양상으로 누난증후군을 터너증후군의 유형으로 잘못 생각하는 경향이 있지만, 사실 터너증후군과는 아주 다른 질환으로서 누난증후군의 염색체는 정상이며, 발생빈도는 1,000-2,500명 당 1명으로 남녀 모두에게 나타난다.

[원인] 누난증후군은 상염색체 우성으로 유전된다. 이것은 누난증후군의 유전자가 성염색체가 아닌 상염색체에 있고, 50%의 가능성으로 부모로부터 아이에게 유전된다는 것을 의미한다. 누난증후군 환자의 50% 정도가 12번 염색체 장완(12q24.1)에 위치하는 NS1 유전자인 PTPN11 (Protein tyrosine phosphatase Nonreceptor-Type11) 유전자의 돌연변이를 보였으며, 그 밖에도 누난증후군과 관련된 여러가지 유전자가 연구중이다.

[임상] 최종 신장이 정상적인 십대 평균치의 하한치에 가까운 작은 키로 남자의 평균신장은 162.5cm, 여자는 157.2cm이다. 선천적인 심장 질환(68%), 폐동맥 협착증(50%), 중격비대(10%), 심실중격결손(5%). 폐동맥관개존중(3%) 외 넓거나 오리물갈퀴 모양의 목, 움푹 들어간 가슴(함몰흉) 또는 비둘기 가슴(돌출형, 방패가슴)을 보인다.

     그리고 남아에서는 고환이 정소에 내려오지 못하는 잠복고환(60%)도 있어 남성의 불임 원인이 될 수도 있다. 태아에서는 주머니 낭종(Nuchal cystic hygroma)도 발견된다. 기타 증상으로는 영유아기에서의 발육장애(40%), 발달상의 지연(26%), 학습장애(15%), 언어지연(20%), 경미한 청력 손실(12%), 경미한 정신지체(35% 이하)를 나타낸다. 혈소판결핍증과 여러가지 응고인자 결핍으로 비정상적으로 멍이 들거나, 출혈되는 경향도 보인다.

       특징적인 외모

  • 얼굴 : 나이가 듦에 따라 세모형태의 얼굴형, 앞머리의 라인이 높고, 주름진 피부곱슬머리
  • 귀 : 아래쪽에 위치하고 뒤쪽으로 돌아간 귀, 신경성 청각장애, 두꺼운 귀/귓바퀴(90%)
  • 눈 : 양안격리, 안검하수(95%), 두꺼운 눈꺼풀, 근시, 청녹색 홍채, 다이아몬드형의 눈썹
  • 입 : 코와 윗입술사이의 깊은 인중, 윗입술의 라인 높고 넓으며(95%), 아치형의 구개(45%), 작은 턱(소악증) (25%)
  • 목 : 익상경과 낮은 머리카락 라인을 가진 목덜미(55%), 낭성 임프관종

[치료] 누난증후군의 치료는 환자에게 나타나는 여러 가지 비정상적 요인들을 제거하는 데 초점을 맞출 수 있다. 저신장의 경우 성장호르몬의 투여로 효과를 거두었다고 보고되었으며, 증상에 따른 외과적인 수술이나 성형수술, 정신과적인 상담, 유전상담 등이 필요하다.



  • 병인: 임신 초기의 유산 원인으로 가장 흔한 염색체 이상으로 자연유산의 25%에서 삼배수성 핵형이 발견된다. 또한 사산이 흔하고, 생아 출산(livebirth)도 가능하지만 그 후 곧 사망하게 된다.
  • 핵형: 3N = 69 chromosomes ---- 69, XXX    69, XXY    rarely 69, XYY; due to a fertilisation anomaly: digyny: non-expulsion of the 2nd polar body; or diandry: fertilisation of 1 oocyte I by 2 spermatozoa. Diandry is 4 times more frequent than digyny.
  • 임상: 전자간증(preeclampsia), 태반이 커서 포기상태(hydatiform mole)가 흔하고, 심한 성장지체(growth retardation), 소두증(microcephaly), 합지증(syndactily), 중뇌(heavy brain)를 보임. 심장, 신장 그리고 안 기형 등으로 인해 사망함.


    염색체 수  4N = 92. 빈도는 유산의 5 %.  문헌상 생아 출산(livebirth)이 보고되기는 하지만 곧 사망