Chromosomes By The Numbers - Adapted From Gc Board Online Review Course

Front 1

chromosome 1

Back 1

del(1)(p36) - straight eyebrows, deep-set eyes, midface hypoplasia, broad and flat nasal rooth/bridge, long philtrum, pointed chin, large late-closing anterior fontanel, microbrachycephaly, epicanthal folds, posterioroly rotated low-set abnormal ears.
-brachy/camptodactyly and short feet
-DD/MR in all, hypotonia
-seizures, structural brain abnlts, heart defects, eye/vision problems, hearing loss, skeletal anomalies

del(1)(q21.1) - TAR syndrome - thrombocytopenia-absent radius synd. - bilat'l radial aplasia w/o absence of thumbs. heart defects, cow's mile intolerance. 25% de novo, 75% inherited from normal parent!

Front 2

chromosome 2

Back 2

del(2)(q37.3) - albright heredtiary osteodystrophy

inv(2)(p11.2q13) - recurring pericentric inversion. No risk of liveborn unbalanced, but increased risk of miscarriages and stillbirths.

Front 3

chromosome 3

Back 3

dup(3)(q26.3) - overlap with Cornelia de Lange.

Front 4

chromosome 4

Back 4

del(4)(p16.3) - Wolf-Hirschhorn syndrome. Severe growth and mental retardation, microcephaly, "greek warrior helmet" face, cleft lip and/or palate. deletions can be large or small, p16.3 is critical region.

t(4;8)(p16;p23) - recurring reciprocal translocation, mediated by olfactory receptor gene clusters on chromosomes 4 and 8. pt with unbalanced der(4) have features of Wolf-Hirschhorn.

Front 5

chromosome 5

Back 5

del(5)(p15) - cri-du-chat syndrome. high pitched cry, microcephaly, severe motor and mental retardation, round face, hypertelorism, micrognathia. Deletion includes p15.31 and/or distal p15.2.

del(5)(q35) - Sotos syndrome. Overgrowth, macrocepy, MR, hypotonia, advanced bone age, typical facies (prominent forehead with recessed hairline, long narrow face, pointed chin, hypertelorism and large ears). Deletions are more common in Japanese (50%) than others (10%). Also caused by mutations in NSD1, which is at 5q35.

Front 6

chromosome 7

Back 6

del(7)(q11.2q11.2) Williams syndrome. contiguous gene syndrome. supravalvular aortic stenosis, "elfin" face, mental and growth retardation, infantile hypercalcemia. Remarkable musical and verbal abilities. Detectable by FISH.

dup(7)(q11.23q11.23) - microdup'n complementary to WS del. mild to mod MR, signif. speech delay, bhvr ass'd w ASD, no reproducible phsyical features
del(7)(q36) - holoprosencephaly. Location of sonic hedgehog.

Front 7

chromosome 8

Back 7

dup(8)(p23.1p23.1) - normal variant and/or ass'n with developmental delay and/or heart defects.

del(8)(q24.11-24.13) - Langer-Giedion syn. Contiguous gene syn - TRPS1, EXT1. MR, microcephaly, multiple exostoses, redundant skin, sparse hair.

inv(8)(p23.1q22.1) - pericentric inversion seen in American Hispanic individuals. carriers have 6% chance of having child with recombinant 8 synd.

t(4;8)(p16;p23) - reccuring balanced translocation, described under chromsome 4.

trisomy 8 - full usually lethal, mosaic reported - MR, poor coordination, prominent forehead, deep set eyes, strabismus, hypertelorism, cleft palate, joint contractures, other skeletal anomalies, deep creases on palms and soles.

Front 8

chromosome 9

Back 8

del(9)(p24) - male to female sex reversal (i.e. 46,XY,del(9)(p24) female). MR, motor delay, trigonocephaly, wide nasal bridge, long fingers and toes.

inv(9)(p11q13) - recurring pericentric inverstion. not ass'd with unbalanced offspring. ass'd with miscarriages and still births.

trisomy 9 mosaicism - severe MR, growth deficiency, sloping forehead, deeply set eyes, joint contractures, heart defects.

Front 9

chromosome 10

Back 9

del(10)(p13-14) - reported in very small number of pt with DiGeorge phenotype. not replicated??

Front 10

chromosome 11

Back 10

dup(11)(p15.5) - BWS - <1% of cases have paternal dup.

del(11)(p13) - ass'd with WAGR (wilms tumor, aniridia, genitoruinary anomalies, MR). contiguous gene syn (aniridia - AN2, wilms and GU - WT1).

del(11)(p11.2) - potocki-shaffer syn. newly recognized del syn. multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, MR.

del(11)(q23) - Jacobsen syn. growth and psychomotor delay, trigonocephaly, strabismus, telecanthus, camptodactyly, thrombocytopenia. Fragile site at this band.

+der(22)t(11;22(q23.3;q11.2) - unbalanced offpsring of carriers of recurring t(11;22) transl'n. double trisomy for proximal 22q and distal 11q. emanuel synd - MR, CHD, malformed ears w tags and/or pits, high arched or cleft palate, micrognathia, anal stenosis or atresia, renal aplasia, genital abnlts in males

inv(11)(q21q23) - recurring peracentric inversion (common in Netherlands and canadian hutterites).

Front 11

chromosome 12

Back 11

+i(12)(p10) - tetrasomy 12p - Pallister-Killian syn. tissue limited mosaicism (in fibroblasts but not lymphocytes). profound MR, seizures, streaky pigmentation, sparse hair (esp. temporal), coarse facial featuers.

Front 12

chromosome 13

Back 12

del(13)(q14.2) - retinoblasatoma - 7% of bilateral cases have del or rearrangement here. RB1 gene is here.

trisomy 13 (Patau syn) - growth retaration, macrocephaly, sloped foreheard, scalp defects, cleft lip/palate, micro or anophthalmia, post axial polydactyly, heart defects, renal anomalies severe CNS malform'n, MR.

Front 13

chromosome 15

Back 13

del(15)(q11-13)pat - del of paternally inherited chromosome 15 that include 15q11.2 cause PWS (70% of cases).

del(15)(q11-13)mat - del of maternally inherited 15 including q11-13 is a cause of Angelman syndrome (70%) of cases.

dup(15)(q11-13)mat - autism and MR. there is also a benign variant duplication that is "cytogenetically indistinguishable."

+inv dup(15) or psu idic(15)(q) - small, often dicentric marker chromosomes. most common identifiable markers/ESACs. if contains probe loci usually del'd in PWS/AS, pt will have MR and autism. if those loci are absent, phenotype may be normal.

Front 14

chromosome 16

Back 14

del(16)(p13.3) alpha-thal/MR syndrome
with broad spectrum of anomalies

del(16)(p13.3) - Rubinstein-Taybi syn.10% of cases have microdeletion. broad thumbs and big toes, MR, small mouth, beaked nose, micrognathia, low hair line, haert defects, skeletal anomalies.

del(16)(p11p11.2) submicroscopic del ass'd with predisposition to autism (seen in autism at greater frequency than controls). ass'd dup also seen in autism.

Front 15

chromosome 17

Back 15

del(17)(p13.3) - Miller-Dieker syn. 90% of pt have del, includes LIS1. microcephaly, lissencephaly, unusual facial appearance, malform'n of heart, kidneys, polydactyly.

del(17)(p13.3) - isolated lissencephaly - 40% of pt have submicroscopic del, includes LIS1.

del(17)(p11.2) - Smith-Magenis-sydnrome. 90% of cases. 5% of cases due to RAI1 mtn. brachycephaly, midface hypoplasia, prognathism, hoarse voice, MR, growth retardation, bhvr problems (self-destructive, self-hugging), sleep disturbances.

dup(17)(p11.2) - SMS region - developmental delay, distinctive physical features.

del(17)(p11.2) - submicroscopic, distal to SMS region. hereditary neuropathy with liability to pressure palsies (HNPP), same region dup'd in CMT1A.

dup(17)(p11.2) - submicroscopic - CMT1A.

del(17)(q21.31) - recurring submicroscopic del ass'd with DD, hypotonia (feeding difficulties), seizures, growth retard'n, abnl facies (long face, ptosis, bulbous nasal tip, hypoplastic nostrils w long columella, broad chin, large low set ears, short philtrum, thin upper lip, protruding tongue)

Front 16

chromosome 18

Back 16

18p- - deletion of all or a large portion of 18p. growth deficiency, MR, hypotonia, microcephaly, holoprosencephaly, micrognathia, large ears.

18q- deletion may be interstitial or terminal. MR, short stature, hypotonia, hearing impairment, foot deformities.

trisomy 18 (Edwards syn) - MR, failure to thrive, heart defects, hypertonia, clenched fists, "rocker-bottom feet," prominent occiput, micrognathia, low-set malformed ears, short palpebral fissures.

Front 17

chromosom 20

Back 17

del(20)(p12.3) - Alagille syn. <7% of cases. JAG1 is at p12.3. mtn in JAG1 cause 88% of cases.

Front 18

chromosome 21

Back 18

del(21)(q22.3) - holoprosencephaly. EHOC1 gene?

trisomy 21 (Down syn) - MR, hypotonia, short stature, brachycephaly with flat occiput, short neck, flat nasal bridge, low-set abnormally folded ears, open mout wiht protruding tongue, upslanting palpebral fissures, epicanthal folds.

Front 19

chromosome 22

Back 19

del(22)(q11.2) - 22q11.2 del. syndrome.

dup(22)(q11.2) - 3-4Mb to 6Mb dup. cleft palate/insufficiency, thymic aplasia, facial features (superior placement of eyebrows, hypertelorism, downslanting palpebral fissures, mild micro-/retrognathia, minor ear anomalies), hearing loss, GU malformations, poor growth, cognitive deficits,

+ idic(22)(q11.2) - cat eye synd. tetrasomy 22q11.2. mild MR, coloboma of iris, downslanting palpebral fissures, preauricular tags or pits, anal atresia.

del(22)(q13) - most are terminal del. infantile hypotonia, normal growth, profound delay, absent or delayted speech, minor dysmorphic features. first found b/c most dels include ARSA, the control probe 22q11.2 del syn.

Front 20

chromosome X

Back 20

del(X)(p22.3p22.3) males w submicroscopic del of steroid sulfatase gene (STS) - x-linked ichthyosis. female carriers not usually affected.

del(X)(p22.3p22.3) - Kallman syndrome - submicroscopic del involving KAL1, rare cause of Kallman syn. hypogonadotropic hypogonadism and anosmia. region is proximal to x-linked ichthyosis region.

dup(X)(p22p22) Pelizaeus-Merzbaucher dis - dismyelinating disorder of CNS. nystagmus, spastic quadriplegia, ataxia, developmental delay.

dup(X)(p21p21) - sex-reversed males. I.e. XY females. duplication of DAX1 gene, suppresses SRY.

Xp (distal) - pseudoautosomal region, including SHOX

Xq13.2 - XIC - initiates expressions of XIST gene on inactive X at Xq13.2

Front 21

Y chromosome

Back 21

inv(Y)(p11;q11) - usually a benign variant. but can be seen in male infertility with accompanying deletion.

distal Yq - mostly heterochromatin