Delineating the 15Q13.3 Microdeletion Phenotype: a Case Series and Comprehensive Review
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SUPPLEMENTARY MATERIAL
Delineating the 15q13.3 Microdeletion Phenotype: A Case Series and Comprehensive Review of the Literature
Supplementary Material / PageTable S1. Results of literature search for 15q13.3 deletion cases / 2-9
Table S2. Full phenotypic details for adult cases with 15q13.3 deletions / See excel attachment
Table S3. Full phenotypic details for child cases with 15q13.3 deletions / See excel attachment
Table S4. Coding key for clinical features listed in Table S2 and S3 / 10-20
Table S5. Obstetric and perinatal outcomes related to 27 cases with 15q13.3 deletions / 21-22
Table S6. Control datasets examined for 15q13.3 (BP4-BP5) deletions / 22-23
Table S7. Control dataset acknowledgments / 24
Table S1. Results of literature search for 15q13.3 deletion cases
Our initial search revealed 55 primary reports containing cases with 15q13.3 deletions.1-55
1.Banka S, Fitzgibbon GJ, Gaunt L, Rankin WJ, Clayton-Smith J. A novel 800 kb microduplication of chromosome 16q22.1 resulting in learning disability and epilepsy may explain phenotypic variability in a family with 15q13 microdeletion. Am. J. Med. Genet. A. Jun 2011;155A(6):1453-1457.
2.Shinawi M, Schaaf CP, Bhatt SS, et al. A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat. Genet. Dec 2009;41(12):1269-1271.
3.Spielmann M, Reichelt G, Hertzberg C, et al. Homozygous deletion of chromosome 15q13.3 including CHRNA7 causes severe mental retardation, seizures, muscular hypotonia, and the loss of KLF13 and TRPM1 potentially cause macrocytosis and congenital retinal dysfunction in siblings. European journal of medical genetics. Jul-Aug 2011;54(4):e441-445.
4.Cubells JF, Deoreo EH, Harvey PD, et al. Pharmaco-genetically guided treatment of recurrent rage outbursts in an adult male with 15q13.3 deletion syndrome. Am. J. Med. Genet. A. Apr 2011;155A(4):805-810.
5.Endris V, Hackmann K, Neuhann TM, et al. Homozygous loss of CHRNA7 on chromosome 15q13.3 causes severe encephalopathy with seizures and hypotonia. Am. J. Med. Genet. A. Nov 2010;152A(11):2908-2911.
6.Liao J, DeWard SJ, Madan-Khetarpal S, Surti U, Hu J. A small homozygous microdeletion of 15q13.3 including the CHRNA7 gene in a girl with a spectrum of severe neurodevelopmental features. Am. J. Med. Genet. A. Nov 2011;155A(11):2795-2800.
7.Lepichon JB, Bittel DC, Graf WD, Yu S. A 15q13.3 homozygous microdeletion associated with a severe neurodevelopmental disorder suggests putative functions of the TRPM1, CHRNA7, and other homozygously deleted genes. Am. J. Med. Genet. A. May 2010;152A(5):1300-1304.
8.Coppola A, Bagnasco I, Traverso M, et al. Different electroclinical picture of generalized epilepsy in two families with 15q13.3 microdeletion. Epilepsia. May 2013;54(5):e69-73.
9.Ben-Shachar S, Lanpher B, German JR, et al. Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. Jun 2009;46(6):382-388.
10.Mikhail FM, Lose EJ, Robin NH, et al. Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders. Am. J. Med. Genet. A. Oct 2011;155A(10):2386-2396.
11.Miller DT, Shen Y, Weiss LA, et al. Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. J. Med. Genet. Apr 2009;46(4):242-248.
12.Hoppman-Chaney N, Wain K, Seger P, Superneau D, Hodge J. Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. Clin. Genet. Apr 2013;83(4):345-351.
13.Rosenfeld JA, Stephens LE, Coppinger J, et al. Deletions flanked by breakpoints 3 and 4 on 15q13 may contribute to abnormal phenotypes. Eur. J. Hum. Genet. May 2011;19(5):547-554.
14.van Bon BW, Mefford HC, Menten B, et al. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J. Med. Genet. Aug 2009;46(8):511-523.
15.Masurel-Paulet A, Andrieux J, Callier P, et al. Delineation of 15q13.3 microdeletions. Clin. Genet. Aug 2010;78(2):149-161.
16.Sharp AJ, Mefford HC, Li K, et al. A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. Nat. Genet. Mar 2008;40(3):322-328.
17.Sharp AJ, Hansen S, Selzer RR, et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat. Genet. Sep 2006;38(9):1038-1042.
18.Mannik K, Parkel S, Palta P, et al. A parallel SNP array study of genomic aberrations associated with mental retardation in patients and general population in Estonia. European journal of medical genetics. Mar-Apr 2011;54(2):136-143.
19.Dibbens LM, Mullen S, Helbig I, et al. Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. Hum. Mol. Genet. Oct 1 2009;18(19):3626-3631.
20.Galizia EC, Srikantha M, Palmer R, et al. Array comparative genomic hybridization: results from an adult population with drug-resistant epilepsy and co-morbidities. European journal of medical genetics. May 2012;55(5):342-348.
21.Heinzen EL, Radtke RA, Urban TJ, et al. Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. Am. J. Hum. Genet. May 14 2010;86(5):707-718.
22.Helbig I, Mefford HC, Sharp AJ, et al. 15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. Nat. Genet. Feb 2009;41(2):160-162.
23.Kevelam SH, Jansen FE, Binsbergen E, et al. Copy number variations in patients with electrical status epilepticus in sleep. J. Child Neurol. Feb 2012;27(2):178-182.
24.McMahon JM, Scheffer IE, Nicholl JK, et al. Detection of microchromosomal aberrations in refractory epilepsy: a pilot study. Epileptic disorders : international epilepsy journal with videotape. Sep 2010;12(3):192-198.
25.Mefford HC, Muhle H, Ostertag P, et al. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. PLoS Genet. May 2010;6(5):e1000962.
26.Muhle H, Mefford HC, Obermeier T, et al. Absence seizures with intellectual disability as a phenotype of the 15q13.3 microdeletion syndrome. Epilepsia. Dec 2011;52(12):e194-198.
27.Kirov A, Dimova P, Todorova A, et al. 15q13.3 microdeletions in a prospectively recruited cohort of patients with idiopathic generalized epilepsy in Bulgaria. Epilepsy Res. May 2013;104(3):241-245.
28.de Kovel CG, Trucks H, Helbig I, et al. Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain. Jan 2010;133(Pt 1):23-32.
29.Guilmatre A, Dubourg C, Mosca AL, et al. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Arch. Gen. Psychiatry. Sep 2009;66(9):947-956.
30.Pagnamenta AT, Wing K, Sadighi Akha E, et al. A 15q13.3 microdeletion segregating with autism. Eur. J. Hum. Genet. May 2009;17(5):687-692.
31.Pinto D, Pagnamenta AT, Klei L, et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature. Jul 15 2010;466(7304):368-372.
32.Shen Y, Dies KA, Holm IA, et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. Apr 2010;125(4):e727-735.
33.Girirajan S, Brkanac Z, Coe BP, et al. Relative burden of large CNVs on a range of neurodevelopmental phenotypes. PLoS Genet. Nov 2011;7(11):e1002334.
34.International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. Sep 11 2008;455(7210):237-241.
35.Levinson DF, Duan J, Oh S, et al. Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Am. J. Psychiatry. Feb 1 2011;168(3):302-316.
36.Stefansson H, Rujescu D, Cichon S, et al. Large recurrent microdeletions associated with schizophrenia. Nature. Sep 2008;455(7210):232-236.
37.Van Den Bossche MJ, Johnstone M, Strazisar M, et al. Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not? American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. Oct 2012;159B(7):812-822.
38.Cooper GM, Coe BP, Girirajan S, et al. A copy number variation morbidity map of developmental delay. Nat. Genet. Sep 2011;43(9):838-846.
39.Girirajan S, Rosenfeld JA, Coe BP, et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N. Engl. J. Med. Oct 4 2012;367(14):1321-1331.
40.Girirajan S, Dennis MY, Baker C, et al. Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Am. J. Hum. Genet. Feb 7 2013;92(2):221-237.
41.Glessner JT, Reilly MP, Kim CE, et al. Strong synaptic transmission impact by copy number variations in schizophrenia. Proc. Natl. Acad. Sci. U. S. A. Jun 2010;107(23):10584-10589.
42.Guha S, Rees E, Darvasi A, et al. Implication of a rare deletion at distal 16p11.2 in schizophrenia. JAMA psychiatry. Mar 2013;70(3):253-260.
43.Kirov G, Pocklington AJ, Holmans P, et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry. Feb 2012;17(2):142-153.
44.Sahoo T, Theisen A, Rosenfeld JA, et al. Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems. Genetics in Medicine. Oct 2011;13(10):868-880.
45.Sanders SJ, Ercan-Sencicek AG, Hus V, et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron. 2011;70:863-885.
46.Williams NM, Zaharieva I, Martin A, et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet. Oct 2010;376(9750):1401-1408.
47.Bergen SE, O'Dushlaine CT, Ripke S, et al. Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder. Mol. Psychiatry. Sep 2012;17(9):880-886.
48.Buizer-Voskamp JE, Muntjewerff JW, Strengman E, et al. Genome-wide analysis shows increased frequency of copy number variation deletions in Dutch schizophrenia patients. Biol. Psychiatry. Oct 1 2011;70(7):655-662.
49.Hehir-Kwa JY, Rodriguez-Santiago B, Vissers LE, et al. De novo copy number variants associated with intellectual disability have a paternal origin and age bias. J. Med. Genet. Nov 2011;48(11):776-778.
50.Kaminsky EB, Kaul V, Paschall J, et al. An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. Genetics in medicine : official journal of the American College of Medical Genetics. Sep 2011;13(9):777-784.
51.Langley K, Martin J, Agha SS, et al. Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants. Br. J. Psychiatry. Nov 2011;199(5):398-403.
52.Nicholl J, Waters W, Suwalski S, et al. Epilepsy with cognitive deficit and autism spectrum disorders: prospective diagnosis by array CGH. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. Jan 2013;162(1):24-35.
53.Stewart LR, Hall AL, Kang SH, Shaw CA, Beaudet AL. High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy. BMC Med Genet. 2011;12:154.
54.Vacic V, McCarthy S, Malhotra D, et al. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature. Mar 24 2011;471(7339):499-503.
55.Williams NM, Franke B, Mick E, et al. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am. J. Psychiatry. Feb 2012;169(2):195-204.
Table S4. Coding key for clinical features listed in Table S2 and S3
ID0 / MR, severity unspecified
1 / Severe
2 / Moderate
3 / Mild
4 / Normal
5 / Learning Difficulties/Disabilities
6 / Cognitive Deficits
7 / Dyslexia
8 / Borderline intellect
DD
1 / Dev. Delay, severity unspecified
2 / Moderate Delay
3 / Language delay
4 / Motor Delay
5 / Cognitive Delay
6 / Motor and Language Delay
7 / Language and Cognitive Delay
8 / Normal
9 / Severe Delay
10 / No motor delay
11 / Mild Delay
Seizure
1 / Seizure, unspecified
2 / Absence/tonic clonic
3 / Grand Mal
4 / Absence
5 / Generalized Tonic-Clonic Seizure
7 / None
8 / Absence/Myoclonus
9 / Myoclonus
10 / Absence/Generalized Tonic-Clonic Seizure
11 / Absence/GTCS/Myoclonus
12 / Myoclonus/GTCS
14 / Absence and pharmacoresistant
15 / Febrile Seizure
16 / Hyperthermic seizure
Epilepsy
1 / Myoclonic
2 / Intractable
3 / No
4 / Juvenile Absence epilepsy/juvenile myoclonic epilepsy
5 / Juvenile Absence epilepsy
6 / Juvenile Myoclonic epilepsy
7 / Idiopathic Epilepsy
8 / Epilepsy, type unspecified
10 / Absence Epilepsy
11 / Generalized Epilepsy
12 / Pharmacoresistant Tonic-Clonic
13 / Idiopathic Absence Epilepsy
14 / Refractory childhood absence epilepsy
15 / Tonic clonic
16 / Primary generalized epilepsy
17 / Landau Kleffner syndrome
EEG
1 / Abnormal
2 / Normal
Autism
1 / Autism
2 / ASD
3 / Normal
4 / Asperger’s Syndrome
5 / PDD-NOS
6 / ASD features
PDD
1 / PDD present
SZ
1 / Schizophrenia
2 / Normal
Family Hx
1 / Present
2 / Absent
Bipolar disorder
1 / Bipolar disorder present
Mood Disorder
1 / Mood disorder, unspecified
2 / Depression
3 / Anxiety
4 / Normal
5 / Oppositional defiant disorder
ADHD
1 / ADHD present
Behaviour
1 / Behaviour Problem
2 / Normal
3 / Obsessive, easily upset, sensitive to sounds
5 / Hyperkinetic
6 / Externalizing problems, withdrawal
8 / Encopresis
9 / Inhibition
10 / Self-mutilation/ Injurious
11 / Hyperphagia
12 / Obsessive, limited social communication
14 / Temper tantrums
15 / Impulsive
16 / Aggressive/Rage
17 / Irritable
18 / Rocking
20 / Borderline personality disorder, narcissistic
21 / Hyperactivity
22 / Poor concentration
23 / Poor attention
Sleeping
1 / Sleeping problem
Cardiovascular
1 / Mitral Valve Prolapse
2 / TOF
3 / Right cardiac hypoplasia with tricuspid stenosis
4 / Normal
5 / Aneurysm of the interauricular septum
6 / Ventricular septal defect
7 / Complex CHD
8 / Abnormal Echo
9 / Normal EKG
10 / Lymphedema
11 / Transient cyanosis
12 / Hypertension
13 / Mild cardiomegaly
14 / Abnormal Echo
15 / MI
16 / CHF
17 / Coronary artery disease
18 / Angina
19 / Normal echo
20 / No heart murmur
21 / Born with hole in heart
Neurology
1 / Abnormal Brain MRI
2 / Normal Brain MRI
3 / Abnormal Neurological Exam
4 / Normal Neurological Exam
5 / Arachnoid Cyst
6 / Vertigo
7 / Tremor
8 / Head Injury
9 / Dyspraxia
11 / Hydrocephalus
12 / Ataxia
14 / Bleed in occipital area
15 / Multilevel degenerative disc disease, spinal stenosis
16 / Acrocephaly/turricephaly
17 / Normal neurological exam
18 / Mild clumsiness
19 / Abnormal CT head without contrast
20 / Normal spine
21 / Choreoathetosis
22 / Lack of coordination
23 / Migraines
24 / Periventricular heterotopia
25 / Poor suck at birth
26 / Feeding difficulties
27 / Stereotypic
Hypotonia
1 / Yes
2 / No
Failure to thrive
1 / Yes
ENT
1 / Hearing problem
Medical Condition
1 / Subcutaneous vessels
2 / Type II diabetes
3 / Fecal Incontinence
4 / Spina bifida occulta
5 / Scoliosis
6 / Right pyelic dialation
7 / UTI
8 / Hypertrichosis
9 / Hiatal hernia
10 / Enuresis
11 / Polycythaemia
12 / Respiratory complications
13 / Jaundice
14 / Hypogammaglobulinemia & recurrent viral infections
15 / Enteritis
16 / Iguinal hernia
17 / GERD
18 / Cryptochridia
19 / Constipation
20 / Ornithine transcarbamylase deficiency
21 / Neutropenia
22 / Mild ileal stenosis
23 / Cavernous hemangioma
24 / Pectus excavatum
25 / Anemia
26 / Hypercalcemia
27 / Osteoporosis
28 / Hyperprolactinemia
29 / Hyperlipidemia
30 / Hypernatremia
31 / Small bowel obstruction
32 / Duodenal ulcer
33 / Osteoarthritis
34 / Breast CA
35 / Hiatal hernia
36 / No testis
37 / Congenital thyroid hypoplasia
38 / Sleep apnea
39 / Tubal ligation
40 / Gallbladder removal
41 / Hypercholesteroemia
42 / Kidney stones
43 / Pneumonia
44 / Hydronephrosis
45 / Carpel tunnel syndrome
46 / Bowel polyps
47 / Tonsillitis
48 / Arthritis
49 / Asthma
50 / Multiple Sclerosis
51 / Hypothyroidism
52 / Basal cell carcinoma
53 / Syringomyelia
Speech
1 / Delay
2 / Poor Vocalization
3 / Nasal
4 / Normal
5 / Mildly dysarthric
6 / Few Sentences
7 / No speech
8 / Articulation Problem
9 / Echolalia
10 / Stuttering
11 / Abnormal Resonance
12 / Impaired
13 / Mildly impaired
14 / Moderately impaired
15 / Limited Speech
16 / Unclear speech
17 / Speech Apraxia
18 / Impaired receptive speech
19 / Normal receptive speech
20 / Impaired expressive speech
21 / Impaired written language
22 / Normal Written language
23 / Speech problem, unspecified
24 / Agrammatism
Eye Pathology
1 / Normal
2 / Myopia
3 / Strabismus
4 / Nystagmus
5 / Retinal dystrophy
6 / Retinal dysfunction
7 / Colobomatous
8 / Visual Impairment
9 / Blepharophismosis
10 / Astigmatism
11 / Asymmetrical optic nerve cupping
12 / Hyperopic, amblyopic, and strabismus
Eye Dysmorphology
1 / Normal
2 / Upslanting palpebral fissures
3 / Normal interpupillary space
4 / Hypertelorism
5 / Synorphris
6 / Asymmetric
7 / Microexotropia
8 / Good eye convergence
9 / Iris coloboma, R eye
10 / Prognathism
11 / Right optic pit, possible coloboma
12 / Epicanthic folds
13 / Deep set eyes
14 / S shaped upper eyelids
15 / Short palpebral fissures
16 / Downslanting palpebral fissures
17 / Ptosis
18 / Long palpebral fissures
19 / Small eyes
20 / Hypotelorism
21 / Bulging eyes
Ear Dysmorphology
1 / Normal
2 / Posterior rotated
3 / Thick helices
4 / Low set
5 / Large
6 / Wide concha
7 / Mildly deficient ear lobules
8 / Folded helices
9 / Protruding
10 / Over folded helices
11 / Long
12 / Antihelix
13 / Hypoplasia
14 / Prominent
15 / Small ears
16 / Large ear lobule
17 / 7 cm, two stabdard deviations above normal
Nose Dysmorphology
1 / Normal
2 / Depressed Nasal bridge
3 / Anteverted Nares
4 / Wide nasal bridge
5 / Prominent
6 / Bulbous tip
7 / Fleshy nose
9 / Prominent nasal tip
10 / Full nasal tip
11 / Pointed columella below the alea
12 / Upward position of nares
13 / Short nose with upturned tip
14 / Broad nasal root
15 / Low nasal bridge
16 / Long, tubular nose
17 / Flat nasal bridge
Philtrum
1 / Normal
2 / Smooth
3 / Short
4 / Prominent
5 / Thick
6 / Flat
Face
1 / Normal
2 / Round
3 / Long
4 / Full
5 / Flat face
6 / Myopathic
7 / High forehead
8 / Grooved chin
9 / Large forehead
10 / Facial dysmorphism, unspecified
11 / Prominent chin
12 / Hypoplasia
13 / Triangular face
14 / Triangular chin
15 / Short forehead
16 / Small
17 / Thin
18 / Flat forehead
19 / No facial dysmorphism
20 / No consistent dysmorphic features
21 / Retrognathia
Lips/Mouth
1 / Normal
2 / Everted lower lip
3 / Full lips
4 / Everted upper lip
5 / Small mouth
6 / Thin upper lip
7 / Large mouth
8 / Protuberant tongue
9 / Narrow palate
10 / Open mouth
Teeth
1 / Normal
2 / Widely spaced
3 / Malocclusion
4 / Small teeth
5 / Delayed eruption
6 / Multiple fillings and cavities
7 / Overcrowded
8 / Multiple dental extractions
9 / Irregular teeth, especially upper central incisors
10 / Small mandible
11 / Excessive fibrotic tissue on maxillary ridge
12 / Teeth removed
13 / Malar hypoplasia
Skin
1 / Normal
2 / Pigmented naevi
3 / Café au lait
4 / Dry
5 / Many birthmarks
6 / Hyper/Hypopigmented macules
7 / Single hypopigmented macules
8 / Eczema
9 / Angioma of the forehead and upper lip
10 / Strawberry hemangioma on arm
11 / Eczema
12 / Normal skin and vasculature
13 / Hypertrichosis
Lower Extremities
1 / Normal
2 / Hallux valgus
3 / Hypoplastic 4th and 5th toes
4 / External rotation of the feet
5 / Patellar luxation
6 / Broad feet
7 / Brachydactyly
8 / Broad toes
9 / Wide sandal gap
10 / Pes planus
11 / Long toes
12 / Large toes
13 / Short toes
14 / Broad lower legs
15 / Pes cavus
16 / Deep plantar creases
17 / Hammer toes
18 / Toenails removed
19 / Morton’s Neuroma
20 / Syndactyly of the 2-3rd digit
Hands
1 / Normal
2 / Stiff fingers
3 / Short fourth metacarpals
4 / Short 5th finger
5 / 5th finger clinodactyly
6 / Tapering fingers
7 / Lax thumb joint
8 / Short palmar crease
9 / Long fingers
10 / Deep palmar crease
11 / Coarse hands
12 / Triphalangeal thumb
13 / Bilateral simian creases
14 / Broad hands
15 / Brachydactyly
16 / Fainted terminal creases
17 / Prominent finger pads
18 / Broad finger tips
19 / Digital findings
20 / Brachymetacarpy
21 / Camptodactyly 4th and 5th fingers
22 / Single palmar crease
23 / Broad Hallux
24 / Short fourth and 5th metacarpals
25 / Short 5th metacarpals
1
Table S5: Obstetric and perinatal outcomes related to 27 cases with 15q13.3 deletions
Obstetric outcomes for probands with the 15q13.3 microdeletion (n=23)No. / ID / Proband age (y) / Sex / Ethnicity / Inheritance / Gestational
age (weeks) / Birth weight (grams) / Birth weight (percentile) / Pregnancy history / Delivery history
1 / Case 231 / Child / F / CAU / de novo / 37 / 2510 / <3a / Partial placenta previa at 34 weeks, unaffected mother developed gestational diabetes / -
2 / Case 229 / Child / M / NR / Unknown / ~32-33 / 2000 / 50 / Placenta previa, premature, pregnancy complicated by asthma, gestational diabetes, and seizure disorder in mother with unknown 15q13.3 deletion status / Emergency Cesarean section
3 / Case 5c / 14 / M / CAU / Maternal / ~32 / 1587 / 25 / Placenta previa, premature / Emergency Cesarean section
4 / Case 21 / 37 / M / CAU / Maternal / Term / NR / NR / Placenta previa, maternal post-partum hemorrhage / Spontaneous vaginal
5 / Case 214 / Child / M / CAU / Maternal / NR / NR / NR / Premature rupture of membranes / Induced vaginal (deterioration in the fetal heart rate)
6 / Case 241 / 8 / M / NR / Unknown / 35 / 2520 / 50 / Premature rupture of membranes at 30 weeks, premature, IUGR / Cesarean section
7 / Case 232 / 9 / F / CAU / de novo / Term / 2550 / <3a / IUGR / -
8 / Case 251 / 1.5 / F / NR / Maternal / 28 / 1100 / 50 / Premature / -
9 / Case 259 / 3.6 / F / NR / Maternal / 34 / NR / NR / Premature / -
10 / Case 248 / 14 / F / NR / Paternal / 42 / 3500 / 50 / Postmature / -
11 / Case 255 / 13 / M / NR / Maternal / 42 / NR / NR / Postmature / -
12 / Case 113 / 44 / M / NR / Maternal / 42 / 3500 / 50 / Postmature / -
Obstetric outcomes for fetuses with the 15q13.3 microdeletion (continued)
No. / ID / Proband age (y) / Sex / Ethnicity / Inheritance / Gestation age (weeks) / Birth weight (grams) / Birth weight (percentile) / Pregnancy history / Delivery history
13 / Case 258 / 3.5 / F / NR / Maternal / NR / NR / NR / Pregnancy induced due to malformation of the fetal heart / -
14 / Case 216 / Child / M / CAU / Maternal / NR / NR / NR / Uncomplicated / Cesarean section (breech)
15 / Case 121 / 8 / F / CAU / Maternal / 41 / 2400 / <3a / - / Emergency cesarean section (fetal distress)
16 / Case 228 / Child / M / NR / Maternal / NR / NR / NR / - / Cesarean section
17 / Case 254 / 4.75 / F / NR / Paternal / 40 / 4400 / >97b / Polyhydramnios / -
18 / Case 114 / 28 / F / NR / Paternal / Term / 4050 / 90b / - / -
19 / Case 191 / 1.5 / F / CAU / Paternal / NR / NR / NR / - / -
20 / Case 247 / 5.5 / M / NR / Maternal / 37 / 4170 / 90b / - / -
21 / Case 250 / 4 / M / NR / Maternal / 40 / 4520 / >90b / - / -
22 / Case 7 / 39 / F / CAU / Unknown / NR / 4224 / b / - / -
23 / Case 257 / 5 / M / NR / Unknown / Term / 3150 / 15-20 / Gestational diabetes / -
Obstetric outcomes for transmitting mothers (n=4)
No. / ID / Age
(y) / Sex / Ethnicity / Inheritance / Obstetric history (deletion status of the fetus where applicable was unknown)
24 / Case 2 / 75 / F / CAU / Unknown / Two spontaneous abortions at age 25 and 26, one male child born at 30 weeks by Cesarean section, and one male stillbirth with nuchal cord
25 / Case 6 / 39 / F / CAU / Unknown / 1 spontaneous abortion
26 / Case 83 / NR / F / CAU / Unknown / 7 spontaneous abortions
27 / Case 4 / 56 / F / CAU / Maternal / Primary infertility
F; female, M; male. CAU; Caucasian , NR; not reported, -; none known; IUGR; intrauterine growth retardation, , asmall for gestational age, blarge for gestational age, cCase 5 is a transmitting mother who developed placenta previa while pregnant with her son who carries 15q13.3 deletion (son not included as a case in this study).