The eight and a half year journey of undiagnosed AD

Gene sequencing and funding of advanced genetic testing has led to hope and new beginnings

Illana Gozes, Marc C. Patterson, Anke Van Dijck, R. Frank Kooy, Joseph N. Peeden, Jacob Eichenberger, Angela Zawacki-Downing, Sandra Bedrosian-Sermone

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Activity-dependent neuroprotective protein (ADNP) is one of the most prevalent de novo mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome. Aim: The aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions. Methods: Longitudinal clinical and parental reports. Results: AD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation. Conclusion: This case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.

Original languageEnglish (US)
Article number107
JournalFrontiers in Endocrinology
Volume8
Issue numberMAY
DOIs
StatePublished - May 19 2017

Fingerprint

Hope
Genetic Testing
Genes
Proteins
Mutation
Imperforate Anus
Exome
Walking
Parents
Magnetic Resonance Imaging
Brain
Therapeutics
Research

Keywords

  • Activity-dependent neuroprotective protein
  • Autism spectrum disorder
  • Case study
  • Motor delays
  • Mutation
  • Nonsense

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

The eight and a half year journey of undiagnosed AD : Gene sequencing and funding of advanced genetic testing has led to hope and new beginnings. / Gozes, Illana; Patterson, Marc C.; Van Dijck, Anke; Kooy, R. Frank; Peeden, Joseph N.; Eichenberger, Jacob; Zawacki-Downing, Angela; Bedrosian-Sermone, Sandra.

In: Frontiers in Endocrinology, Vol. 8, No. MAY, 107, 19.05.2017.

Research output: Contribution to journalArticle

Gozes, Illana ; Patterson, Marc C. ; Van Dijck, Anke ; Kooy, R. Frank ; Peeden, Joseph N. ; Eichenberger, Jacob ; Zawacki-Downing, Angela ; Bedrosian-Sermone, Sandra. / The eight and a half year journey of undiagnosed AD : Gene sequencing and funding of advanced genetic testing has led to hope and new beginnings. In: Frontiers in Endocrinology. 2017 ; Vol. 8, No. MAY.
@article{d8a1c290b4594066b785d3c78e92c8d8,
title = "The eight and a half year journey of undiagnosed AD: Gene sequencing and funding of advanced genetic testing has led to hope and new beginnings",
abstract = "Background: Activity-dependent neuroprotective protein (ADNP) is one of the most prevalent de novo mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome. Aim: The aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions. Methods: Longitudinal clinical and parental reports. Results: AD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation. Conclusion: This case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.",
keywords = "Activity-dependent neuroprotective protein, Autism spectrum disorder, Case study, Motor delays, Mutation, Nonsense",
author = "Illana Gozes and Patterson, {Marc C.} and {Van Dijck}, Anke and Kooy, {R. Frank} and Peeden, {Joseph N.} and Jacob Eichenberger and Angela Zawacki-Downing and Sandra Bedrosian-Sermone",
year = "2017",
month = "5",
day = "19",
doi = "10.3389/fendo.2017.00107",
language = "English (US)",
volume = "8",
journal = "Frontiers in Endocrinology",
issn = "1664-2392",
publisher = "Frontiers Media S. A.",
number = "MAY",

}

TY - JOUR

T1 - The eight and a half year journey of undiagnosed AD

T2 - Gene sequencing and funding of advanced genetic testing has led to hope and new beginnings

AU - Gozes, Illana

AU - Patterson, Marc C.

AU - Van Dijck, Anke

AU - Kooy, R. Frank

AU - Peeden, Joseph N.

AU - Eichenberger, Jacob

AU - Zawacki-Downing, Angela

AU - Bedrosian-Sermone, Sandra

PY - 2017/5/19

Y1 - 2017/5/19

N2 - Background: Activity-dependent neuroprotective protein (ADNP) is one of the most prevalent de novo mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome. Aim: The aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions. Methods: Longitudinal clinical and parental reports. Results: AD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation. Conclusion: This case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.

AB - Background: Activity-dependent neuroprotective protein (ADNP) is one of the most prevalent de novo mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome. Aim: The aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions. Methods: Longitudinal clinical and parental reports. Results: AD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation. Conclusion: This case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.

KW - Activity-dependent neuroprotective protein

KW - Autism spectrum disorder

KW - Case study

KW - Motor delays

KW - Mutation

KW - Nonsense

UR - http://www.scopus.com/inward/record.url?scp=85020006338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020006338&partnerID=8YFLogxK

U2 - 10.3389/fendo.2017.00107

DO - 10.3389/fendo.2017.00107

M3 - Article

VL - 8

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

IS - MAY

M1 - 107

ER -