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17p13.3 microduplication syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	Dup(17)(p13.3) Trisomy 17p13.3 17p13.3 duplication syndrome
Number of Symptoms	19
OrphanetNr:	217385
OMIM Id:	613215
ICD-10:	Q92.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	No data available.
Inheritance:	Unknown Not applicable [Orphanet]
Age of onset:	Neonatal Infancy [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
-Rare developmental defect during embryogenesis
-Rare genetic disease
Partial duplication of the short arm of chromosome 17
-Rare developmental defect during embryogenesis
-Rare genetic disease
Rare intellectual deficit with developmental anomaly
-Rare neurologic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000054)	Micropenis	Occasional [Orphanet]	257 / 7739
2	(HPO:0000445)	Wide nose	Very frequent [Orphanet]	190 / 7739
3	(HPO:0002007)	Frontal bossing	Very frequent [Orphanet]	366 / 7739
4	(HPO:0000316)	Hypertelorism	Very frequent [Orphanet]	644 / 7739
5	(HPO:0000160)	Narrow mouth	Very frequent [Orphanet]	188 / 7739
6	(HPO:0002705)	High, narrow palate	Occasional [Orphanet]	308 / 7739
7	(HPO:0000494)	Downslanted palpebral fissures	Frequent [Orphanet]	328 / 7739
8	(HPO:0003196)	Short nose	Very frequent [Orphanet]	264 / 7739
9	(HPO:0000348)	High forehead	Very frequent [Orphanet]	157 / 7739
10	(HPO:0000470)	Short neck	Frequent [Orphanet]	345 / 7739
11	(HPO:0000357)	Abnormal location of ears	Frequent [Orphanet]	328 / 7739
12	(HPO:0001385)	Hip dysplasia	Occasional [Orphanet]	242 / 7739
13	(HPO:0004209)	Clinodactyly of the 5th finger	Occasional [Orphanet]	288 / 7739
14	(HPO:0004299)	Hernia of the abdominal wall	Occasional [Orphanet]	176 / 7739
15	(HPO:0000098)	Tall stature	Occasional [Orphanet]	74 / 7739
16	(HPO:0001252)	Muscular hypotonia	Very frequent [Orphanet]	990 / 7739
17	(HPO:0002119)	Ventriculomegaly	Occasional [Orphanet]	253 / 7739
18	(HPO:0007370)	Aplasia/Hypoplasia of the corpus callosum	Occasional [Orphanet]	180 / 7739
19	(HPO:0012758)	Neurodevelopmental delay	Very frequent [Orphanet]	949 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Bi et al. (2009) reported 7 unrelated individuals with different submicroscopic duplications of chromosome 17p13.3 involving the LIS1 and/or YWHAE genes. Four individuals had a duplication of YWHAE but not LIS1, and 1 had a duplication of LIS1 ... Bi et al. (2009) reported 7 unrelated individuals with different submicroscopic duplications of chromosome 17p13.3 involving the LIS1 and/or YWHAE genes. Four individuals had a duplication of YWHAE but not LIS1, and 1 had a duplication of LIS1 but not YWHAE. A sixth patient had a triplication of LIS1, and a seventh had duplication of both genes. Analysis of the clinical features for each individual indicated that individuals with LIS1 duplications had subtle brain defects, including microcephaly, dysgenesis of the corpus callosum, and cerebellar atrophy, as well as neurobehavioral disorders, including delayed development, mental retardation, and attention deficit-hyperactivity disorder. Patients with duplications of YWHAE tended to have macrosomia, facial dysmorphism, and mild developmental delay. Transgenic mice overexpressing Lis1 showed decreased brain size and distorted cellular organization in the ventricular zone. Bi et al. (2009) concluded that variations in dosage of LIS1 play a role in the development of brain anomalies in humans and mice. Roos et al. (2009) used multiplex ligation-dependent probe amplification (MLPA) or array CGH analysis to identify 3 developmentally delayed children with duplications of chromosome 17p13, ranging in size from 1.8 to 4.0 Mb, with a 1.8-Mb region of overlap. All duplications included the 8 genes in the MDS critical region: PRP8 (607300), RILP (607848), SREC (SCARF1; 607873), PITPNA (600174), SKIP (603055), MYO1C (606538), CRK (164762), and YWHAE. All patients had hypotonia and mild to moderate psychomotor retardation. One had overgrowth, with a marfanoid habitus. Dysmorphic features were present in all 3 patients, including frontal bossing, low-set ears, broad nasal bridge, small nose, hypertelorism, downslanting palpebral fissures, broad and flat midface, and triangularly-shaped chin. The second child, a girl, showed failure to thrive and poor growth. The third child, a boy, also had micropenis, right-sided inguinal hernia, and hypermobility. Brain MRI revealed hypoplasia of the corpus callosum, dilated lateral ventricles, and a suggestion of thinning of the white matter. None of the patients had lissencephaly or gross brain malformations. Bruno et al. (2010) identified 3 unrelated individuals with a pathogenic microduplication of 17p13.3 from a larger cohort of 7,678 patients who underwent microarray screening for learning difficulties and/or autism with or without other congenital anomalies. Two additional patients from this cohort carried microduplications which were present in unaffected family members, and were thus considered nonpathogenic. Including the patients reported by Bi et al. (2009) and Roos et al. (2009), Bruno et al. (2010) suggested that there are 2 classes of microduplications of 17p13.3. Class I duplications involve YWHAE, but not PAFAH1B1, whereas class II duplications involve PAFAH1B1 and may also include CRK and YWHAE. Class I duplications are associated with autistic features and other behavioral symptoms, speech and motor delay, subtle dysmorphic facial features such as pointed chin and cupid bow, subtle hand/foot malformations, and a tendency to postnatal overgrowth. Class II microduplications are associated with moderate to mild developmental and psychomotor delay and hypotonia. Some dysmorphic features, such as prominent forehead and pointed chin, are shared with the class I duplications. Notably, individuals with duplication of PAFAH1B1 but not YWHAE or CRK show microcephaly and severe growth restriction, but are not particularly dysmorphic. All the breakpoints were nonrecurrent.

Symptoms & Signs

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