3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder

Julien Thevenon; Patrick Callier; Hélène Poquet; Iben Bache; Bjorn Menten; Valérie Malan; Maria Luigia Cavaliere; Jean-Paul Girod; Christel Thauvin-Robinet; Salima El Chehadeh; Jean-Michel Pinoit; Frederic Huet; Bruno Verges; Jean-Michel Petit; Anne-Laure Mosca-Boidron; Nathalie Marle; Francine Mugneret; Alice Masurel-Paulet; Antonio Novelli; Zeynep Tümer; Bart Loeys; Stanislas Lyonnet; Laurence Faivre

doi:10.1136/jmedgenet-2013-101939

3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder

Julien Thevenon, Patrick Callier, Hélène Poquet, Iben Bache, Bjorn Menten, Valérie Malan, Maria Luigia Cavaliere, Jean-Paul Girod, Christel Thauvin-Robinet, Salima El Chehadeh, Jean-Michel Pinoit, Frederic Huet, Bruno Verges, Jean-Michel Petit, Anne-Laure Mosca-Boidron, Nathalie Marle, Francine Mugneret, Alice Masurel-Paulet, Antonio Novelli, Zeynep TümerBart Loeys, Stanislas Lyonnet, Laurence Faivre

Medical Genetics Program

8 Citations (Scopus)

Abstract

Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions. Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome. Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/ 4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway. Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.

Original language	English
Journal	Journal of Medical Genetics
Volume	51
Issue number	1
Pages (from-to)	21-7
Number of pages	7
ISSN	0022-2593
DOIs	https://doi.org/10.1136/jmedgenet-2013-101939
Publication status	Published - Jan 2014

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Thevenon, J., Callier, P., Poquet, H., Bache, I., Menten, B., Malan, V., Cavaliere, M. L., Girod, J-P., Thauvin-Robinet, C., El Chehadeh, S., Pinoit, J-M., Huet, F., Verges, B., Petit, J-M., Mosca-Boidron, A-L., Marle, N., Mugneret, F., Masurel-Paulet, A., Novelli, A., ... Faivre, L. (2014). 3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder. Journal of Medical Genetics, 51(1), 21-7. https://doi.org/10.1136/jmedgenet-2013-101939

3q27.3 microdeletional syndrome : a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder. / Thevenon, Julien; Callier, Patrick; Poquet, Hélène et al.

In: Journal of Medical Genetics, Vol. 51, No. 1, 01.2014, p. 21-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Thevenon, J, Callier, P, Poquet, H, Bache, I, Menten, B, Malan, V, Cavaliere, ML, Girod, J-P, Thauvin-Robinet, C, El Chehadeh, S, Pinoit, J-M, Huet, F, Verges, B, Petit, J-M, Mosca-Boidron, A-L, Marle, N, Mugneret, F, Masurel-Paulet, A, Novelli, A, Tümer, Z, Loeys, B, Lyonnet, S & Faivre, L 2014, '3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder', Journal of Medical Genetics, vol. 51, no. 1, pp. 21-7. https://doi.org/10.1136/jmedgenet-2013-101939

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title = "3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder",

abstract = "Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions. Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome. Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/ 4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway. Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.",

author = "Julien Thevenon and Patrick Callier and H{\'e}l{\`e}ne Poquet and Iben Bache and Bjorn Menten and Val{\'e}rie Malan and Cavaliere, {Maria Luigia} and Jean-Paul Girod and Christel Thauvin-Robinet and {El Chehadeh}, Salima and Jean-Michel Pinoit and Frederic Huet and Bruno Verges and Jean-Michel Petit and Anne-Laure Mosca-Boidron and Nathalie Marle and Francine Mugneret and Alice Masurel-Paulet and Antonio Novelli and Zeynep T{\"u}mer and Bart Loeys and Stanislas Lyonnet and Laurence Faivre",

year = "2014",

month = jan,

doi = "10.1136/jmedgenet-2013-101939",

language = "English",

volume = "51",

pages = "21--7",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

publisher = "B M J Group",

number = "1",

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TY - JOUR

T1 - 3q27.3 microdeletional syndrome

T2 - a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder

AU - Thevenon, Julien

AU - Callier, Patrick

AU - Poquet, Hélène

AU - Bache, Iben

AU - Menten, Bjorn

AU - Malan, Valérie

AU - Cavaliere, Maria Luigia

AU - Girod, Jean-Paul

AU - Thauvin-Robinet, Christel

AU - El Chehadeh, Salima

AU - Pinoit, Jean-Michel

AU - Huet, Frederic

AU - Verges, Bruno

AU - Petit, Jean-Michel

AU - Mosca-Boidron, Anne-Laure

AU - Marle, Nathalie

AU - Mugneret, Francine

AU - Masurel-Paulet, Alice

AU - Novelli, Antonio

AU - Tümer, Zeynep

AU - Loeys, Bart

AU - Lyonnet, Stanislas

AU - Faivre, Laurence

PY - 2014/1

Y1 - 2014/1

N2 - Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions. Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome. Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/ 4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway. Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.

AB - Background Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions. Methods We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome. Results The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5<N<25)) (4/ 4), arachnodactyly (3/4) and pectus excavatum (2/4)). This phenotype could be explained by the deletion of the AHSG gene, which encodes a secreted protein implicated in bone maturation and the TGFb signalling pathway. Conclusions We report on a new microdeletional syndrome that associates with a recognisable facial dysmorphism and marfanoid habitus including scoliosis, neuropsychiatric disorders of the psychotic spectrum and moderate to severe ID.

U2 - 10.1136/jmedgenet-2013-101939

DO - 10.1136/jmedgenet-2013-101939

M3 - Journal article

C2 - 24133203

SN - 0022-2593

VL - 51

SP - 21

EP - 27

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 1

ER -

3q27.3 microdeletional syndrome: a recognisable clinical entity associating dysmorphic features, marfanoid habitus, intellectual disability and psychosis with mood disorder

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