 |
 |
-
sSMC formed by
McClintock-mechanism -
START
by chromosomal origin for sSMC formed by McClintock mechanism
| sSMC 1 |
sSMC 2 |
sSMC 3 |
sSMC 4 |
sSMC 5 |
sSMC 6 |
sSMC 7 |
sSMC 8 |
| sSMC 9 |
sSMC 10 |
sSMC 11 |
sSMC 12 |
sSMC 13 |
sSMC 14 |
sSMC 15 |
sSMC 16 |
| sSMC 17 |
sSMC 18 |
sSMC 19 |
sSMC 20 |
sSMC 21 |
sSMC 22 |
sSMC X |
sSMC Y |
References
| "In one of
her seminal contributions Barbara McClintock
describes the mechanism leading to the
formation of ring/deleted chromosomes in
maize and the aberrant mitotic behaviour
leading to 'variable mutant
characteristics'. This mechanism, a break
within the centromere together with a break
in either the long or the short arm,
creating a small ring, has been called
"centromere misdivision"; these authors
propose that this be referred to as "the
McClintock mechanism". McClintock also
describes pachytene configurations in
microsporocytes, showing that although the
normal, deleted and ring chromosomes may
synapse, the ring is also seen with the
centromeric region attached to a
non-homologous bivalent." (cited from Mantzouratou et al., Molecular Cytogenetics 2009, 2:3) |
|
by chromosomal origin for sSMC formed by pseudo-McClintock mechanism However, it turned out that similar to McClintock mechanism with ring chromosome formation, there are cases which seem to evolve by a related mechnaism, called pseudo-McClintock mechansim. |
| case no. |
gender/ age at diagnosis |
studied material |
de novo/ inherited |
GTG-banding
result grade of mosaicism |
final result
of the sSMC |
test methods |
clinical
symptoms |
Reference |
|
McCl- 01- N- p32/ 1-1 |
male/ 38y |
PBL/ fibro- blasts |
n.a. |
47,XY,del(1)(p32p36.1), +mar1[87]/ 47,XY,del(1)(p32p36.1), +mar2[10]/ 46,XY,del(1)(p32p36.1)[3] (fibroblasts: 95/5/0; plus a t(X;4)(q23;q13)) |
mar1
= r(1)(::p32→p36.1::)/ mar2 = r(1)(::p32→p36.1: :p23→p36.1::) |
pan-centromeric probe, telomeric probe, wcp1 probe; UPD-test | infertility and oligospermia; otherwise normal male | {1-5; 58} |
|
Neocentric/
healthy
McCl- 01- N- p21/ 1-1 |
n.a./ postnatal |
PBL | n.a. | 47,XN,del(1)(p21p13),+mar |
r(1)(::p21→p13::) | FISH | n.a., presumably normal | {59} 1 case |
|
Healthy
McCl- 01- N- p13/ 1-1 |
male/ 39y |
PBL | n.a. | 47,XY,del(1)(p13p11.1), +mar[100%] |
r(1)(::p13→p11.1::) |
M-FISH; MCB,
ceps |
normal male,
infertile |
{70} case 1 |
|
Neocentric/
unclear
McCl- 01- N- q23/ 1-1 |
male/ prenatal |
AF | de novo | 47,XY,del(1)(q23q32), +mar[20] |
r(1)(::q23→q32::) "dynamic mosaic" i.e. variants of sSMC were detected but not characterized in detail |
wcp1; cep1/5/19; all centromere probe | Amniocentesis due to advanced maternal age; no ultrasound abnormalities; pregnancy terminated. | {3-6} |
|
McCl- 02- O- p12/ 1-1 |
male/ adult |
PBL | de novo | 47,XY,del(2)(p12p11.1), +mar[100%]* |
r(2)(::p12→p11.1::) FISH-data: RP11-316G9 = AC009958.3 (89.6 MB) and RP11-294I29 = AQ508381 (88.9MB) on sSMC |
cen2, wcp2, YACs as specified in {11} | Man was studied due to a child with a phenotype resembling Down-syndrome; child had karyotype 46,XY,del(2)(p10p12) | {0} {8} |
|
Neocentric/
abnormal
McCl- 02- N- p21/ 1-1 |
male/ 14y |
PBL | de novo | 47,XY,del(2)(p21p11), +mar[100%] |
r(2)(::p21→p11::) | wcp2, pan-centromeric probe; telomeric probe | moderately mental retarded, at 32y weight and OFC at 25. centile; narrow forehead, broad supraorbital ridges, large mouth, marked hyperkyphosis, moderately hyperactive, IQ = 50 | {3; 9-11} |
|
Neocentric/
abnormal
02- N- q22/ 1-1 |
female/ postnatal |
PBL (EKF- cellbank) |
n.a. | 47,XX,del(2)(q22q32.2), +r(2)(q22q32.2)[81]/ 46,XX, del(2)(q22q32.2)[9] |
r(2)(::q22→q32.2::) | midi | mental retardation | {12} 1 case |
|
Neocentric/
abnormal
02- N- q32.1/ 1-1 |
male/ 6m |
PBL |
de novo |
see
below |
r(2)(::q32.1→q36.1::) arr[GRCh37] 2q23.1q36.1 (186,698,504_223,918,111)x3 |
aCGH, wcp, BACs | muscular hypotonia | {0}
provided from Leipzig, Germany |
| 47,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::)[4]/47,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::q36.1->q32.1::)
or
der(2)(::q32.1->q36.1::q36.1->q32.1::)[3]/ 48,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::q36.1->q32.1::) or der(2)(::q32.1->q36.1::q36.1->q32.1::)x2[1]/48,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::),+r(2)(::q32.1->q36.1::q36.1->q32.1::) or der(2)(::q32.1->q36.1::q36.1->q32.1::)[7]/ 49,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::),+r(2)(::q32.1->q36.1::q36.1->q32.1::),+der(2)(::q32.1->q36.1::q36.1->q32.1::)[1]/ 49,XY,del(2)(q32.1q36.1),+r(2)(::q32.1->q36.1::),+r(2)(::q32.1->q36.1::q36.1->q32.1::) order(2)(::q32.1->q36.1::q36.1->q32.1::)x2[2] |
||||||||
|
McCl- 03- W- p11/ 1-1 |
male/ 26y |
PBL/ fibro- blasts |
de novo | 47,XY,del(3)(p11q11), +mar[28]/ 46,XY,del(3)(p11q11)[12] mar present in 100% of skin fibroblasts |
min(3)(:p11→q11:) Neocentromere formation in 3q26 on del(3) chromosome. |
wcp3; cep3 | The male was
considered to have borderline mental
retardation, and was detected due to his
newborn daughter with developmental delay,
hypertelorism, epicanthus. She inherited
only the del(3) chromosome. |
{13; 14; 15 case 1} |
|
McCl- 04- W- p16.1/ 1-1 |
male/ 42y |
PBL | n.a. | 47,XY,+mar[3]/ 46,XY[14] |
r(4)(::p16.1→p14:) Neocentromere formation in 3q26 on del(3) chromosome. |
midi | normal male,
prinary infertility |
{0,
67} case P3 |
|
Abnormal
McCl- 04- W- p15.3/ 1-1 |
male/ prenatal |
AF | de novo | 47,XY, del(4)(p15.3q21.1), +r[96]/ 46,XY,del(4)(p15.3q21.1)[4] |
r(4)(::p15.3→q21.1::) | cep 4, sub-telomeric probe 4q; WHS probe | see below | {16} |
| Amniocentesis due to ultrasound detection of advanced nuchal translucency, echogenic bowel, short femurs, mild ventricular dilatation; IUGR at 5. centile; at week 32 oligohydramnion; at week 33 no fetal movements and intrauterine death confirmed at week 34; on delivery bay 640g ([lt]0.4 centile) and macerated; detectable were anal atresia, neck webbing, umbilical cord with two vessels | ||||||||
|
Healthy
McCl- 04- W- p12/ 1-1 |
female/ adult |
PBL | n.a.; same mar imbalanced in child | 47,XX,+mar[67%]/ 46,XX[33%] |
47,XX,del(4)(p12q10), +r(4)(::p12→q10::)[66%]/ 46,XX,del(4)(p12q10)[33%]* size 4.4 MB |
centr. probes, centr.-near probes; aCGH | see below | {17} {18} case 7 |
| child with mild speech delay; no dysmorphic features; normal motor development; Mother is intellectually normal with unilateral ear anomalies and mild visual deficiencies | ||||||||
|
Unclear
McCl- 04-W- q10/ 1-1 |
female/ prenatal |
AF | de novo | 47,XX,+mar[9]/ 46,XX[5] |
47,XX,del(4)(q11q13), +r(4)(::q11→q13::)[66%]/ 46,XX,del(4)(q11q13)[33%]* size 22 MB |
aCGH | advanced maternal age; TOP | {60} |
|
Neocentric/
abnormal
McCl- 04-W- q12/ 1-1 |
male/ 6m |
PBL | de novo | 47,XY,del(4)(q12q21.1)+mar[5]/ 46,XX,del(4)(q12q21.1)[25] |
+r(4)(::q12→q21.1::) arr(hg19): 56,288,188-77,876,928 |
aCGH | DYS, skin
pigmentaton, DD, growth delay |
{66} |
|
Neocentric/
abnormal
McCl- 04- N- q22.1/ 1-1 |
male/ 17y |
PBL/ fibro- blasts |
de novo | 47,XY,del(4)(q21.1q21.3), +mar[75%]/ 46,XY,del(4)(q21.1q21.3)[25%]* |
r(4)(::q21.1→q21.3::)* sSMC derived from maternal chromosome 4 |
midi; telomeric probes, YACs; UPD-test | see below |
{19; 3-5} |
| neonatal eczema, multiple infections; studied due to Hyper-IGE syndrome with recurrent infections (HIES); motor, language, social and developmental milestones of patient delayed; mother of patient borderline to mental retardation, autism | ||||||||
|
Neocentric/
abnormal
McCl- 04- N- q26/ 1-1 |
female/ prenatal |
AF NIPT |
n.a. | 47,XX,+mar[23]/ 46,XX[21] |
r(4)(::q26→q31.21::)* |
NIPT | VSD; no
further info available |
{71}
case SJ015 |
|
McCl- 05- W- p13/ 1-1 |
male/ 27y |
PBL | n.a. | 47,XY,del(5)(p13q10), +r[68]/ 46,XY,del(5)(p13cen)[2] |
r(5)(::p13→q10: :p13→q10::) |
cep 1/5/19; YAC 897G2 | see below | {20} |
| Birth weight 3500g (50th centile), OFC 38cm (>95. centile); length 50cm (25. centile); square asymmetric skull, plagioturricephaly, facial asymmetry, hypertelorism, epicantal folds, short and broad nose, long, deep philtrum, microretrognathism, high palate, low-set abnormal ears, clinodactyly 5, simian crease, hypotonia, omphalocoele, inguinal hernias, club feet; at 20m weight at 90. centile OFC >97. psychomotor development delayed. | ||||||||
|
Healthy
McCl- 05- W- p11/ 1-1 |
male/ prenatal |
AF, PBL |
de novo | 47,XY,del(5)(p11p13), +mar[100%] after array: 47,XY,der(5)(pter→p15.31: :pter→p14.3::p11→qter), +r(5)(::p11→q13.2::) |
r(5)(::p11→q13.2::) array: 5p15.33-p15.31 (131,945-6,267,160)x3, 5p14.3-p13.2 (21,438,495- 36,736,934)x1, 5p12-p11 (42,529,343- 45,908,725)x3 |
BAC-FISH, aCGH | amniocentesis due to advanced maternal age; normal male at birth and at 1.5y | {54} |
|
McCl- 06- O- p22.3/ 1-1 |
male/ 43y |
PBL | n.a. | 47,XY,del(6)(p10p22.3), +r(6)(::p10→p22.3::)[100%] |
r(6)(::p22.3→q10::)* | wcp6, cep 6, subtel 6p and 6q | normal male apart from infertility | {21} {22} case 10 |
|
Healthy
McCl- 06- O- p11.2~ p11.1/ 1-1 |
female/ 37y |
PBL | de novo | 47,XX,del(6)(p11.2~p11.1q12), +r(?6)[80%]/ 46,XX[20%] |
r(6)(::p10→q12::)[60%]/ r(6)(::p11.2~p11.1 →q12::)[20%] |
midi/ subcenM |
normal, but two abnormal children with mar | {58} |
|
Healthy
McCl- 06- O- p10/ 1-1 |
female/ 30y |
PBL | n.a. | 47,XX,del(6)(p10q13), +r(6)[?%]/ 46,XX[?%] |
r(6)(::p10→q13::) array: 77.23-96.63MB |
MCB, aCGH | normal, but one abnormal children with mar | {55} mother of patient 2 |
|
Neocentric/
healthy
McCl- 06- N- q16.2/ 1-1 |
male/ adult |
PBL | de novo? | 47,XY,t(4;15),del(6)(q16.2q22.2), +r(6)(::q16.2→q22.2::)[100%] |
r(6)(::q16.2→q22.2::) |
all centromeres, wcp probes, sub-telomere 6q |
mar detected due to phenotypically abnormal child of propositus; child had karyotype 46,t(4;15),del(6)(q16.2q22.2)[100%] | {5; 23-24} |
|
McCl- 07- N- p22/ 1-1 |
male/ 2y |
PBL | de novo | 47,XY,del(7)(p22q21.2),+ |
r(7)(p22q21.2)
|
cep 7 | DD, DYS, growth retardation | {62} |
|
Neocentric/
abnormal
McCl- 07- N- q22/ 1-1 |
male/ newborn |
AF/ PBL |
de novo | AF:
47,XY,+r(7)(q22q31)[10]/46,XY[7] PBL: sSMC only in 28% of cells unusual complex McClintock mechanism |
r(7)(q22q31) | M-FISH aCGH |
DD, DYS, growth retardation, MR | {63} |
|
McCl- 08- O- p11.1/ 1-1 |
male/ adult |
PBL | de novo | 47,XY,del(8)(p11.1q12.1),+r(8)(p11.1q12.1)[18]/ 46,XY[2] |
r(8)(::p11.1→q12.1::)* neocentromere in 8p22 in der(8) |
aCGH, cep 8 | normal male, sSMC detected due to child with clinical abnormalities due to lacking sSMC |
{25; 53; 58} |
|
Healthy
McCl- 08- O- p11.1/ 2-1 |
male/ adult |
PBL | n.a. | 47,XY,del(8)(p23q10),+r(8)(p23q10)[55]/46,XY,del(8)(p23q10)[5] | r(8)(::p23→q10::) |
NGS, cep 8 | infertile | {65} case
1 |
|
McCl- 09- N- q31/ 1-1 |
female/ adult |
PBL | n.a. | 47,XX,del(9)(q31q33),+r(9)(q31q33)[60%]/ 46,XX,del(9)(q31q33)[40%] |
r(9)(::q31→q33::) | aCGH; BAC FISH | mild degree of mental retardation (IQ 69); sSMC detected due to child with a 46,XY,del(9)(q31q33)[100%] and mild psychomotor retardation | {30} |
|
Unclear
McCl- 09- N- q10/ 1-1 |
female/ ?adult |
PBL | n.a. | 47,XX,del(9)(q10porq?),+r(9)(q10porq?) | n.a. | wcp 9 | mental retardation | {56} |
|
McCl- 10- W- p11.23/ 1-1 |
male/ 4y10m |
PBL | inv dup (13 or 21) paternal derived | 48,XY,del(10),+r(?10), +inv dup(acro)[100%] double rings in 4-8% of the cells |
del(10)
= der(10)(pter→p11.23: :q23.2→qter) r(?10) = r(10)(::p11.23→q23.2::) inv dup(acro) = inv dup(13or 21) |
cep10, 13/21; 14/22; 15; 5 different alpha sat.- probes; satIII probe | developmental delay at 4y, delayed speech development, normal motor activity, not dysmorphic; height, length and HC ~25. centile | {3-4; 10; 31-39} |
|
Neocentric/
abnormal
McCl- 10- N- q11/ 1-1 |
female/ 1w |
AF/ fibro- blasts |
de novo | 47,XX,del(10)(q11q23),+mar[62%]/ 46,XX,del(10)(q11q23)[38%] (sSMC in 80% of fibroblasts) |
?min(10)(:q11→q23:) (without detectable telomeres) |
alpha-, beta-satellite satIII,telomeric, all wcp, YAC-probes (not specified) | mental retardation and/or developmental delay or structural anomalies detected at birth | {26} case
8 {3-5, 10} |
|
McCl- 11-O- p15.1/ 1-1 |
female/ newborn |
PBL fibro- blasts |
maternal | PBL:
47,XX,del(11)(p15.1p11.1), +r(11)(p15.1p11.1)[70%]/ 46,XX,del(11)(p51.1p11.1)[30%] In fibroblasts: marker in 50% |
r(11)(::p15.1→p11.1::)* | cep 11 | severely dysmorphic; Turner-like phenotype with classical bilateral aniridia, microcephaly, Fallot tetralogy; mother with aniridia as well - here mar in 70% of the blood cells; otherwise normal | {40} |
|
Neocentric/
abnormal
McCl- 11-N- p14.3/ 1-1 |
female/ 36y |
PBL | n.a. | mos 47,XX,del(11)(p14.3p11.2),+r[16]/46,XX,del(11)(p.14.3p11.2)[4] | r(11)(::p14.3→neo→11.12::) | SNP-aCGH without details provided | Normal herself, but abnormal fetus with del(11) only | {68} |
|
Neocentric/
abnormal
McCl- 11- N- p11.2/ 1-1 |
female/ adult |
PBL | n.a. | 47,XX,del(11)(p11.12p11.2),+mar[100%] | r(11)(::p11.12→p11.2::) | n.a. | normal - sSMC detected due to clinical abnormalities in a child | {5; 7} |
|
McCl- 12- U p13.1/ 1-1 |
female/ 3m |
PBL | maternal | 47,XX,del(12)(p13.1→q10),+r[100%] | r(12)(::p13.1→q10::) | wcp12 | mother normal?; child? | {27} |
|
McCl- 13/21-‘ U- p11.1/ 1-1 |
see 13/21-U-4 - similar to a McClintock mechanism, but not the same | |||||||
|
Neocentric/
healthy
McCl- 13- N- q12.3/ 1-1 |
male/ 29y |
PBL | n.a. | 47,XX,del(13)(q12.3q22), +mar[97]/46,XX,del(13)(q12.3q22)[3] |
r(13)(::q12.3→q22::) | wcp, array-CGH | normal male; fertility problems | {51; 57; 58} |
|
Neocentric/
healthy
McCl- 13- N- q21.31/ 1-1 |
female/ 32y |
PBL | de novo | 47,XX,del(13)(q21.32q22.2), +mar[100%] |
r(13)(::q21.31→q22.2::) | midi; telomeric probe | normal female; sSMC detected due to 3 miscarriages | {4-5, 29-30; 42} |
|
Neocentric/
abnormal
McCl- 13- N- q31.1/ 1-1 |
male/ 1m (?) |
PBL | de novo | 47,XY,del(13)(q31.1q32.3), +r(13)(::q31.1q32.3::)[50%]/ 46,XY,del(13)(q31.1q32.3)[50%] |
r(13)(::q31.1→q32.3::) | BAC-probes | moderate intellectual disability associated with distinctive hand malformations (hypoplastic and angel-shaped middle phalanges) and partial growth hormone (GH) deficiency at 13 y | {5; 28} |
|
McCl- 14- N- q12/ 1-1 |
female/ 18y |
PBL | n.a. | 47,XX,del(14)(q12q24.3), +r(14)(q12q24.3) |
r(14)(::q12→q24.3::) | sequencing; FISH |
MR, DD, tetraplegia, osteoporosis, no speach, seizures, DYS | {61} |
|
McCl- 15- N- q11.1/ 1-1 |
male/ 14y |
PBL | n.a. | 47,XY,del(15)(q11.1q21.1), +r(15)(q11.1q21.1) |
r(15)(::q11.2→q21.1::) | FISH | Marfan
syndrome like infertile |
{64} |
|
Neocentric/
unclear
McCl- 15- N- q11.1/ 2-1 |
female/ prenatal |
CH, AF |
de novo |
47,XX,+21[12]/ 48,XX,+21,+mar[3] |
r(15)(::q25.2→q25.3:) | aCGH | Down
syndrome,. TOP |
{69} |
|
McCl- 16- W- p10/ 1-1 |
female/ 23y |
PBL | n.a. | 47,XX,del(16)(p10q13), +r(16)(::p10→q13::)[100%]* | r(16)(::p10→q13::) | n.a. | mild general hypotonia, HC 51cm = very small; bow shaped mouth, abnormal posteriorly rotated ears; apart from that normal; detected due to a malformed child without the mar but with the del(16) chromosome | {43} |
|
McCl- 16- W- q13/ 1-1 |
male/ 8y |
PBL | n.a. | 47,XX,del(16)(q13q23), +r(16)(::q13→q23::)[100%]* | r(16)(::q13→q23::) | aCGH, MCB |
short stature, speech delay | {70} case
5 |
|
McCl- 17- O- p11.2/ 1-1 |
moved to PsMcCl-17-O-p11.2/1-1 | |||||||
|
Healthy
McCl- 17- U- p10/ 1-1 |
female/ 82y |
PBL skin fibro- blasts |
de novo | 48,XX,del(17)(p10q11.2),+r[2%]/
47,XX,del(17)(p10q11.2),+r[~75%]/
47,XX,del(17)(p10q11.2),+r(dic)[12%]/
47,XX,del(17)(p10q11.2),+mar[~5%]/ 46,XX,del(17)(p10q11.2)[6%]* similar in blood and fibroblasts; |
marker derived from (17)(p10q11.2) | centromeric probe for chromosome 17 | no congenital malformations; suffering from neurofibromatosis type 1 since age of 40y; neither her parents nor her children had NF1. Children with normal karyotypes. | {47} |
|
McCl- 19- W- p10/ 1-1 |
male/ 1m(?) |
PBL | maternal 47,XX,del(19) (p10q13.2),+r(19) | 47,XY,+r[100%] | r(19)(::p10→q13.2::)* | FISH probe wcp 19 | see below | {48} |
| Delivery in week 37 because of maternal blood hypertension; birth weight 2280g; overweight syndrome at 3-4y → every mensurartions were more than 3S.D. except for the length. Additionally macrocephaly, hypertelorism, antimongoloid slants, bluish ring around the eyes, globular prominent nose, abnormal mouth, large ears, arms and legs short and podgy, mental retardation (DQ=69) | ||||||||
|
McCl- 22- O- q11.1/ 1-1 |
female/ 44y |
PBL | n.a. | 47,XX,del(22)(p11.1q11.2) +mar[16]/ 46,XX,del(22)(p11.1q11.2) |
r(22)(::q10q11.2::) | DiGeorge CR-probe; array-CGH | normal female; mar detected due to repeated children with heart defects | {52; 58} |
|
Abnormal
McCl- 22- W- q11.2/ 2-1 |
male/ infant |
PBL | maternal 47,XX,del(22)(q11q11.2), +r(22)(q10q11.2) |
47,XY,+mar[100%] | r(22)(::q10q11.2::) | cep probes; TUPLE1 probe | CHARGE association | {49} |
|
McCl- 0X- W- p21/ 2-1 |
female/ 1y |
PBL | de novo | 47,X,del(Xq),+r[20%]/ 46,X,del(Xq)[80%] in fibroblasts. 40/10 |
del(X)
= der(X)(pter→q21.1: :p21→pter) r = r(X)(::p21→ q11~12::) |
cep X; wcp X; pericentric probes; STS, KAL; UBE1XIST specific probe | see below | {50} |
| pregnancy and birth normal; birth weight 30. centile; length 10. centile; OFC 25. centile; syndactyly of right finger 3 and 4 and left toes 4 and 5; cardiac murmur due to ventricular and artrial septal defect and patent ductus arteriousus plus pulmonary stenosis; agenesis of corpus callosum, mild cerebral ventricular dilatation; a t 1y severely handicapped, no speech, hypotonia, broad face, short neck, prominent forehead, telecanthus, convergent strabismus, small abnormal nose, prominent inverted V-shaped upper lip, short philtrum, low set and mildly posteriorly rotated ears | ||||||||
|
Abnormal
McCl- 0X- W- q27.1/ 1-1 |
male/ 4.5y |
PBL | n.a. | 47,XY,+mar[35]/ 46,XY |
r(X)(q27.1q28) | aCGH | see below | {0} provided by family |
| in
sonography enhanced nuchal transluciency;
born normal; at 2 months reflux, at 6 months
growth retardation (lenght 0.4th centile),
DD, i.e. crawling with 20 months, walking at
2 years; at 4.5 years only 2 word sentences;
slight dysmorphism; small head,
hypogonadotropic hypogonadism; now under
groth hormons.
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