Chromosome Mutations: Structural Aberrations (cyto)

Monosomy 1p36

Key clinical features:

Mental retardation, growth delay,

hypotonia, early puberty, deafness, eye

problems, cardiomyopathy, seizures

and/or abnormal EEGs, enlarged anterior

fontanel, deep-set eyes, flat nasal bridge,

orofacial clefting or palatal abnormalities,

pointed chin, ear abnormalities

Wolf-Hirschhorn

Key clinical features: Mental and growth retardation,

microcephaly, hypertelorism, broad nasal bridge,

downturned mouth, cleft lip and/or palate, micrognathia,

cryptorchidism, hypospadias

4p

Wolf-Hirschhorn

Deleted region:

Cri du chat

Key clinical features:

Mental and growth

retardation, cat-like cry in

infancy, microcephaly, round

face, hypertelorism,

down-slanting palpebral

fissures

5p

Cri du chat

Deleted region:

Sotos

Key clinical features: Cardinal features include intellectual disability,

overgrowth, and characteristic long, thin facies with a broad forehead,

sparse frontoparietal hair, and down-slanted palpebral fissures.

Macrocephaly, advanced bone age, behavior problems, hypotonia,

feeding problems, renal anomalies, scoliosis, and seizures are also see

5q35

Sotos

Deleted region:

Williams

Key clinical features: Mental retardation, short stature,

supravalvular aortic stenosis, hypercalcemia, friendly

disposition, hoarse voice, periorbital fullness, stellate pattern

in the iris, anteverted nares, long philtrum, full lip

7q11.23

Williams

Deleted region:

Potocki-Shaffer

Key clinical features: Mental retardation, biparietal foramina,

brachycephaly, turricephaly, multiple exostoses, micropenis, and

minor facial dysmorphism including a high forehead, small

upturned nose with broad tip, downturned mouth

11p11.2

Potocki-Shaffer

Deleted region:

Jacobsen

Key clinical features: Mental and growth retardation,

trigonocephaly, strabismus, cardiac defects, digit anomalies,

thrombocytopenia

11q24.1–11qter

Jacobsen

Deleted region:

Langer-Giedion

Key clinical features: Mental and growth retardation, multiple exostoses,

cone-shaped epiphyses, fine scalp hair, bulbous nose, prominent ears, simple

but prominent philtrum, loose redundant skin in infancy

8q24.11–8q24.13

Langer-Giedion

Deleted region:

Angelman

Key clinical features: Mental and growth retardation, frequent laughter,

ataxia and jerky arm movements, seizures, maxillary hypoplasia, deep-set

eyes, large mouth with protruding tongue, widely spaced teeth, prognathia

Maternal 15q11.2–15q13.1

Angelman

Deleted region:

Prader-Willi

Key clinical features: Mental and growth retardation, hypotonia and feeding

problems in infancy, later obesity associated with hyperphagia, narrow

bifrontal diameter, almond-shaped eyes, small hands and feet, hypogonadism,

skin picking

Paternal 15q11.2–15q13.1

Prader-Willi

Deleted region:

15q13.3 Microdeletion

Key clinical features: Developmental delay with mild to moderate learning

disability, autism spectrum disorder, schizophrenia, epilepsy, seizures, digit

anomalies, and facial features that include hypertelorism, short philtrum, and

a thick, everted upper lip. Extensive phenotypic variability and incomplete

penetrance have been reported

15q13.3

15q13.3 Microdeletion

Deleted region:

Rubinstein-Taybi

Key clinical features: Mental retardation, postnatal growth retardation,

hypotonia, broad thumbs and toes, cryptorchidism, abnormal facies with

downward-slanting palpebral fissures; heavy, highly arched eyebrows; long

eyelashes; prominent and/or beaked nose; hypoplastic maxilla with narrow

palate

16p13.3

Rubinstein-Taybi

Deleted region:

Miller-Dieker

Key clinical features: Mental and growth retardation, lissencephaly,

microcephaly, bitemporal depression, long philtrum, thin upper lip, mild

micrognathia, ear dysplasia, anteverted nostrils

17p13.3

Miller-Dieker

Deleted region:

Hereditary neuropathy with liability

to pressure palsies (HNPP)

Key clinical features: Asymmetric recurrent palsies precipitated by focal

pressure beginning in the second or third decade of life and electrophysiologic

findings of prolonged sensory motor nerve conduction

17p11.2 deletion complementary to

the CMT1A syndrome duplication

Hereditary neuropathy with liability

to pressure palsies (HNPP)

Deleted region:

Smith-Magenis

Key clinical features: Mental retardation, behavioral problems,

hyperactivity, sleep disturbance, decreased pain sensitivity, short stature,

brachycephaly, midface hypoplasia, prognathism, fingertip pads, hoarse voice

17p11.2

Smith-Magenis

Deleted region:

17q21.3 Microdeletion

Key clinical features: Mental retardation/developmental delay, delayed

speech, friendly disposition, hypotonia, normal growth, epilepsy, heart

anomalies, renal/urologic anomalies, abnormal hair color or texture, and

typical facies with high broad forehead, ptosis, blepharophimosis, up-slanting

palpebral fissures, epicanthal folds, a tubular- or pear-shaped nose,

prominent ears

17q21.3 deletion complementary to the 17q21.2

microduplication syndrome

17q21.3 Microdeletion

Deleted region:

Alagille

Key clinical features: Cholestasis, peripheral pulmonic stenosis, vertebral

arch defects, posterior embryotoxon, abnormal facies including deep-set eyes,

broad forehead, long straight nose, prominent chin, small low-set or

malformed ears

20p12.2

Alagille

Deleted region:

DiGeorge

Key clinical features: Learning disabilities, short stature, overt or

submucous cleft palate, velopharyngeal incompetence, prominent nose with

squared nasal root and narrow alar base, conotruncal cardiac defects, and

psychiatric disorders in some

22q11.2 deletion complementary to proximal 22q11.2

microduplication syndrome

DiGeorge

Deleted region:

Phelan-Mcdermid

Key clinical features: Moderate to severe developmental delay, severe

expressive speech delay, behavior disturbance, increased tolerance to pain,

hypotonia, normal to accelerated growth, dysplastic toenails, large hands, and

minor dysmorphic features including dolichocephaly, ptosis, abnormal ears,

pointed chin

22q13.3

Phelan-Mcdermid

Deleted region:

Kallmann

Key clinical features: Hypogonadotropic hypogonadism, eunuchoid habitus,

anosmia or hyposmia, bimanual synkinesis

Xp22.3

Kallmann

Deleted region:

Ichthyosis (X-linked)

Key clinical features: Hypertrophic ichthyosis, corneal opacities without

impairment of vision

Xp22.3

Ichthyosis (X-linked)

Deleted region:

Beckwith-Wiedemann

Key clinical features: Macrosomia, macroglossia, organomegaly,

omphalocele, ear creases, hypoglycemia, tumor susceptibility. Beckwith-

Wiedemann patients with cytogenetic duplications are more likely to have

learning difficulties

11p15.5 b (Paternal)

Beckwith-Wiedemann

Duplicated region:

Pallister-Killian

Key clinical features: Mental retardation, streaks of hyper- and

hypopigmentation, sparse anterior scalp hair, sparse eyebrows and eyelashes,

prominent forehead, protruding lower lip, coarsening of face with age

Mosaic tetrasomy 12p usually secondary to an

extra metacentric isochromosome

Pallister-Killian

Duplicated region:

Proximal 15q11.2 Microduplication

Key clinical features: Mild to severe intellectual impairment particularly with

regard to language, autism spectrum disorders, decreased motor

coordination, hypotonia, reduced deep tendon reflexes, joint laxity, mild or no

dysmorphic features. Phenotype typically associated with maternal (but not

paternal) duplication

15q11.2 15q13.1a Complementary to Prader-Willi/

Angelman syndrome deletion region

Proximal 15q11.2 Microduplication

Duplicated region:

Pseudodicentric 15 (“inverted duplicated 15”)

Key clinical features: Mental and growth retardation, autism, behavioral

disturbance, seizures, low posterior hairline, epicanthal folds, low-set ears,

strabismus The smaller pseudodicentric 15 chromosomes may not cause

phenotypic abnormalities

Tetrasomy 15pter–15q13 due to the presence of an

extra pseudodicentric chromosome

Pseudodicentric 15 (“inverted duplicated 15”)

Duplicated region:

17p13.3 Duplication

Key clinical features: Most are unique nonrecurrent duplications that

overlap with but do not correspond to the recurring Miller-Dieker syndrome

deletion region Mental retardation and/or learning difficulties, speech

difficulties, autism, hypotonia, subtle hand and foot malformations, lack of

severe congenital anomalies, and normal to increased growth parameters.

Facial features include prominent forehead and pointed chin

17p13.3

17p13.3 Duplication

Duplicated region:

Charcot-Marie-Tooth 1A (CMT1A)

Key clinical features: Abnormal nerve conduction velocities, distal muscle

weakness, muscle atrophy, and sensory loss. Symptoms begin between ages 5

and 25 and progress slowly

17p11.2 duplication complementary to the HNPP

syndrome deletion

Charcot-Marie-Tooth 1A (CMT1A)

Duplicated region:

Potocki-Lupski

Key clinical features: Mild to borderline mental retardation, behavioral

problems, hypotonia, failure to thrive, cardiac anomalies, and variable

dysmorphic features that include triangular face, frontal bossing,

microcephaly, hypertelorism, wide nasal bridge, epicanthal folds, and a flat

philtrum

17p11.2 duplication complementary to the

Smith-Magenis syndrome deletion

Potocki-Lupski

Duplicated region:

17q21.3 Duplication

Key clinical features: Intellectual disability, autism spectrum disorders, and

variable dysmorphic features

17q21.3 b Duplication complementary to the

17q21.3 microdeletion syndrome

17q21.3 Duplication

Duplicated region:

Proximal 22q11.2 Microduplication

Key clinical features: Currently no clearly established phenotype recognized.

Some patients noted to have features that overlap with DiGeorge syndrome

including mental retardation and developmental delay, abnormalities of the

palate, conotruncal heart defects, absent thymus, and corresponding T-cell de

ficiency. Phenotype variable and ranges from mild to severe

22q11.2 duplication complementary to the

DiGeorge syndrome deletion.

Proximal 22q11.2 Microduplication

Duplicated region:

Cat Eye Tetrasomy

Key clinical features: Usually mild mental retardation, coloboma of the iris,

down-slanting palpebral fissures, preauricular tags and/or fistulas, anal

atresia

22q11.2 (occasionally trisomy) usually secondary

to an extra pseudodicentric or ring chromosome

Cat Eye Tetrasomy

Duplicated region: