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GeneDx, Rett/Angelman Syndrome and Related Disorders Panel
MessageCollect at NMCP only Mon-Thursday by 1200
Test Code
729
Alias/See Also
Rett/Angelman Syndrome and Related Disorders Genetic Testing Panel Sequence Analysis* and Exon-level Deletion/Duplication** Testing of 11 Genes
CPT Codes
81302x1, 81404x1, 81406x2
Includes
Genes: CDKL5, CNTNAP2, FOXG1, MBD5, MECP2, MEF2C, NRXN1, SLC9A6, TCF4, UBE3A, ZEB2
Preferred Specimen
Whole blood in EDTA. Adults: 8-10 ml; Children: 4 ml; Infants: 2 ml.
Instructions
Ship overnight at ambient temperature, using a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.
Transport Temperature
ambient
Methodology
Exon Array CGH, Next-gen Sequencing
Report Available
14-16 weeks
Clinical Significance
"The Rett/Angelman Syndrome and Related Disorders Panel at GeneDx includes 11 genes that cause disorders
with overlapping clinical phenotypes including epilepsy, developmental delay, and intellectual disability. A brief
summary of the specific clinical features of these disorders is included below.
Rett syndrome is a progressive neurodevelopmental disorder that primarily affects females. Classic Rett
syndrome is characterized by apparently normal development in the first 6-18 months followed by an arrest in
development and subsequent regression in language and motor skills. Frequent symptoms include loss of
speech and purposeful hand use, stereotypic hand movements, ataxia, microcephaly, and seizures. Multiple
forms of atypical (variant) Rett syndrome have been described, including early-onset Rett syndrome with
seizures beginning before six months, forme fruste Rett syndrome with a milder and more slowly progressive
course, and the preserved speech variant with a milder clinical phenotype including retained verbal abilities and
hand use.1 Congenital Rett syndrome is a severe congenital encephalopathy that affects males and females
and is characterized by hypotonia, irritability, and unresponsiveness in the neonatal period with seizures,
progressive microcephaly and developmental delay/regression noted in the first few months of life.2,3
Angelman syndrome (AS) is characterized by developmental delay with absent or significantly impaired speech,
intellectual disability, ataxia, microcephaly, a characteristic EEG pattern, and a typical behavioral pattern
including a happy personality with outbursts of laughter, hyperactivity, excitability, sleep problems, and handflapping
movements.4,5 Facial features often observed in individuals with AS include a prominent chin, a wide
mouth with a protruding tongue. Angelman-like (Christianson) syndrome is characterized by intellectual
disability, ataxia, severe speech and language impairment, epilepsy, and microcephaly in males.6,7,8
Pitt-Hopkins syndrome (PHS) is characterized by severe intellectual disability with absent or severely delayed
speech that is often associated with breathing abnormalities, stereotypic movements, seizures, microcephaly
and a characteristic facial gestalt consisting of coarse facial features, deep-set eyes, a broad or beaked nasal
bridge, a large mouth with a tented upper lip and widely spaced teeth, and cup-shaped ears with a thick
helix.9,10,11 Ataxia, short stature, constipation, gastroesophageal reflux, strabismus, and nonspecific
abnormalities on brain MRI have also been described.9,10,11
Mowat-Wilson syndrome (MWS) is characterized by severe expressive language delay, seizures, moderate to
severe intellectual disability, and a typical facial gestalt consisting of uplifted earlobes with a central depression,
broad and medially thick eyebrows, hypertelorism, downslanting palpebral fissures, an open-mouthed
expression, and an elongated face with prognathism.12,13 Hirschsprung disease (HSCR), congenital heart
defects, microcephaly, ataxia, urogenital anomalies, short stature, structural eye anomalies, and
hypoplasia/agenesis of the corpus callosum have also been described in more than half of patients with MWS.12"
with overlapping clinical phenotypes including epilepsy, developmental delay, and intellectual disability. A brief
summary of the specific clinical features of these disorders is included below.
Rett syndrome is a progressive neurodevelopmental disorder that primarily affects females. Classic Rett
syndrome is characterized by apparently normal development in the first 6-18 months followed by an arrest in
development and subsequent regression in language and motor skills. Frequent symptoms include loss of
speech and purposeful hand use, stereotypic hand movements, ataxia, microcephaly, and seizures. Multiple
forms of atypical (variant) Rett syndrome have been described, including early-onset Rett syndrome with
seizures beginning before six months, forme fruste Rett syndrome with a milder and more slowly progressive
course, and the preserved speech variant with a milder clinical phenotype including retained verbal abilities and
hand use.1 Congenital Rett syndrome is a severe congenital encephalopathy that affects males and females
and is characterized by hypotonia, irritability, and unresponsiveness in the neonatal period with seizures,
progressive microcephaly and developmental delay/regression noted in the first few months of life.2,3
Angelman syndrome (AS) is characterized by developmental delay with absent or significantly impaired speech,
intellectual disability, ataxia, microcephaly, a characteristic EEG pattern, and a typical behavioral pattern
including a happy personality with outbursts of laughter, hyperactivity, excitability, sleep problems, and handflapping
movements.4,5 Facial features often observed in individuals with AS include a prominent chin, a wide
mouth with a protruding tongue. Angelman-like (Christianson) syndrome is characterized by intellectual
disability, ataxia, severe speech and language impairment, epilepsy, and microcephaly in males.6,7,8
Pitt-Hopkins syndrome (PHS) is characterized by severe intellectual disability with absent or severely delayed
speech that is often associated with breathing abnormalities, stereotypic movements, seizures, microcephaly
and a characteristic facial gestalt consisting of coarse facial features, deep-set eyes, a broad or beaked nasal
bridge, a large mouth with a tented upper lip and widely spaced teeth, and cup-shaped ears with a thick
helix.9,10,11 Ataxia, short stature, constipation, gastroesophageal reflux, strabismus, and nonspecific
abnormalities on brain MRI have also been described.9,10,11
Mowat-Wilson syndrome (MWS) is characterized by severe expressive language delay, seizures, moderate to
severe intellectual disability, and a typical facial gestalt consisting of uplifted earlobes with a central depression,
broad and medially thick eyebrows, hypertelorism, downslanting palpebral fissures, an open-mouthed
expression, and an elongated face with prognathism.12,13 Hirschsprung disease (HSCR), congenital heart
defects, microcephaly, ataxia, urogenital anomalies, short stature, structural eye anomalies, and
hypoplasia/agenesis of the corpus callosum have also been described in more than half of patients with MWS.12"
