Editing Rett syndrome (section)

==Signs and symptoms==
===Stage I===
Stage I, called early-onset, typically begins between 6 and 18 months of age.<ref name=NIH2017/> This stage is often overlooked because symptoms of the disorder may be somewhat vague, and parents and doctors may not notice the subtle slowing of development at first.<ref name=NIH2017/> The infant may begin to show less eye contact and have reduced interest in toys. There may be delays in gross motor skills such as sitting or crawling.<ref name=NIH2017/> Hand-wringing and decreasing head growth may occur, but not enough to draw attention. This stage usually lasts for a few months but can continue for more than a year.<ref name=NIH2017/>

===Stage II===
Stage II, or the rapid destructive stage, usually begins between ages 1 and 4 and may last for weeks or months.<ref name=NIH2017/> Its onset may be rapid or gradual as the child loses purposeful hand skills and spoken language.<ref name=NIH2017/> Characteristic hand movements such as wringing, washing, clapping, or tapping, as well as repeatedly moving the hands to the mouth often begin during this stage which is called mouthing.<ref name=NIH2017/> The child may hold the hands clasped behind the back or held at the sides, with random touching, grasping, and releasing.<ref name=NIH2017/> The movements continue while the child is awake but disappear during sleep.<ref name=NIH2017/> Breathing irregularities such as episodes of apnea and hyperventilation may occur, although breathing usually improves during sleep.<ref name=NIH2017/> Some girls also display autistic-like symptoms such as loss of social interaction and communication.<ref name=NIH2017/> Walking may be unsteady and initiating motor movements can be difficult. Slowed head growth is usually noticed during this stage.<ref name=NIH2017/>

===Stage III===
Stage III, or the plateau or pseudo-stationary stage, usually begins between ages 2 and 10 and can last for years.<ref name=NIH2017/> [[Apraxia]], motor problems, and [[seizure]]s are prominent during this stage.<ref name=NIH2017/> However, there may be improvement in behavior, with less irritability, crying, and [[autistic]]-like features.<ref name=NIH2017/> In stage III there may be more interest in the surroundings and alertness, attention span, and communication skills may improve.<ref name=NIH2017/> Many girls remain in this stage for most of their lives.<ref name=NIH2017/>

===Stage IV===
Stage IV, or the late motor deterioration stage, can last for years or decades.<ref name=NIH2017/> Prominent features include reduced mobility, [[scoliosis|curvature of the spine]], and muscle weakness, rigidity, spasticity, and increased muscle tone with abnormal posturing of an arm or leg.<ref name=NIH2017/> Girls who were previously able to walk may stop walking.<ref name=NIH2017/> Cognition, communication, or hand skills generally do not decline in stage IV.<ref name=NIH2017/> Repetitive hand movements may decrease and eye gaze usually improves.<ref name=NIH2017/>

===Variants===
The signs and symptoms of the typical form of the Rett syndrome are well described.
In addition to the classical form of Rett syndrome, several atypical forms have been described over the years;<ref>{{Cite journal |last1=Neul |first1=Jeffrey l.  |last2=Kaufmann |first2=Walter E. |last3=Glaze |first3=Daniel G. |last4=Christodoulou |first4=John |last5=Clarke |first5=Angus J. |last6=Bahi-Buisson |first6=Nadia |last7=Leonard |first7=Helen |last8=Bailey |first8=Mark E. S. |last9=Schanen |first9=N. Carolyn |year=2010 |title=Rett syndrome: Revised diagnostic criteria and nomenclature |journal=Annals of Neurology |volume=68 |issue=6 |pages=944–50 |doi=10.1002/ana.22124 |pmc=3058521 |pmid=21154482 |last10=Zappella |first10=Michele |last11=Renieri |first11=Alessandra |last12=Huppke |first12=Peter |last13=Percy |first13=Alan K. |collaboration=Rettsearch Consortium}}</ref> the main groups are:
* Congenital variant (Rolando variant): in this severe subtype of Rett syndrome, the development of the patients and their head circumference are abnormal from birth.<ref>{{Cite journal |last1=Ariani |first1=Francesca |last2=Hayek |first2=Giuseppe |last3=Rondinella |first3=Dalila |last4=Artuso |first4=Rosangela |last5=Mencarelli |first5=Maria Antonietta |last6=Spanhol-Rosseto |first6=Ariele |last7=Pollazzon |first7=Marzia |last8=Buoni |first8=Sabrina |last9=Spiga |first9=Ottavia |date=11 July 2008 |title=FOXG1 is Responsible for the Congenital Variant of Rett Syndrome |journal=The American Journal of Human Genetics |volume=83 |issue=1 |pages=89–93 |doi=10.1016/j.ajhg.2008.05.015 |pmc=2443837 |pmid=18571142 |last10=Ricciardi |first10=Sara |last11=Meloni |first11=Ilaria |last12=Longo |first12=Ilaria |last13=Mari |first13=Francesca |last14=Broccoli |first14=Vania |last15=Zappella |first15=Michele |last16=Renieri |first16=Alessandra}}</ref> The typical gaze of Rett syndrome patients is usually absent;
* [[Michele Zappella|Zappella]] variant of Rett Syndrome or preserved speech variant: in this subtype of Rett syndrome the patients acquire some manual skills and language is partially recovered around the age of 5 years (that is after the regression phase). Height, weight and head circumference are often in the normal range, and a good gross motor function can be observed.<ref>{{Cite journal |last=Zappella |first=Michele |s2cid=4782923 |year=1992 |title=The rett girls with preserved speech |journal=Brain and Development |volume=14 |issue=2 |pages=98–101 |doi=10.1016/S0387-7604(12)80094-5 |pmid=1621933}}</ref><ref>{{Cite journal |last1=Skjeldal |first1=O. H. |last2=Von Tetzchner |first2=S. |last3=Jacobsen |first3=K. |last4=Smith |first4=L. |last5=Heiberg |first5=A. |year=2007 |title=Rett Syndrome - Distribution of Phenotypes with Special Attention to the Preserved Speech Variant |journal=Neuropediatrics |volume=26 |issue=2 |pages=87 |doi=10.1055/s-2007-979732 |pmid=7566462|s2cid=260243402 }}</ref><ref>{{Cite journal |last1=Sørensen |first1=E. |last2=Viken |first2=B. |date=20 February 1995 |title=[Rett syndrome a developmental disorder. Presentation of a variant with preserved speech] |journal=Tidsskrift for den Norske Laegeforening |language=no |volume=115 |issue=5 |pages=588–590 |issn=0029-2001 |pmid=7900110}}</ref><ref>{{Cite journal |last=Zappella |first=M |year=1997 |title=The preserved speech variant of the Rett complex: A report of 8 cases |journal=[[European Child & Adolescent Psychiatry]] |volume=6 |issue=Suppl 1 |pages=23–5 |pmid=9452915}}</ref><ref>{{Cite journal |last1=Renieri |first1=A. |last2=Mari |first2=F. |last3=Mencarelli |first3=M.A. |last4=Scala |first4=E. |last5=Ariani |first5=F. |last6=Longo |first6=I. |last7=Meloni |first7=I. |last8=Cevenini |first8=G. |last9=Pini |first9=G. |date=March 2009 |title=Diagnostic criteria for the Zappella variant of Rett syndrome (the preserved speech variant) |journal=Brain and Development |volume=31 |issue=3 |pages=208–16 |doi=10.1016/j.braindev.2008.04.007 |pmid=18562141 |last10=Hayek |first10=G. |last11=Zappella |first11=M.|s2cid=6223422 }}</ref><ref>{{Cite journal |last1=Buoni |first1=Sabrina |last2=Zannolli |first2=Raffaella |last3=De Felice |first3=Claudio |last4=De Nicola |first4=Anna |last5=Guerri |first5=Vanessa |last6=Guerra |first6=Beatrice |last7=Casali |first7=Stefania |last8=Pucci |first8=Barbara |last9=Corbini |first9=Letizia |date=May 2010 |title=EEG features and epilepsy in MECP2-mutated patients with the Zappella variant of Rett syndrome |journal=[[Clinical Neurophysiology (journal)|Clinical Neurophysiology]] |volume=121 |issue=5 |pages=652–7 |doi=10.1016/j.clinph.2010.01.003 |pmid=20153689 |last10=Mari |first10=Francesca |last11=Renieri |first11=Alessandra |last12=Zappella |first12=Michele |last13=Hayek |first13=Joseph|s2cid=12976926 }}</ref> The Zappella variant is a milder form of Rett syndrome;
* Hanefeld variant or early epilepsy variant. In this form of Rett syndrome, the patients have epilepsy before 5 months of age.<ref>{{cite journal |doi=10.1016/S0387-7604(03)00018-4 |title=The spectrum of phenotypes in females with Rett Syndrome |year=2003 |last1=Huppke |first1=Peter |last2=Held |first2=Melanie |last3=Laccone |first3=Franco |last4=Hanefeld |first4=Folker |s2cid=9566219 |journal=Brain and Development |volume=25 |issue=5 |pages=346–51 |pmid=12850514}}</ref>
The definition itself of the Rett syndrome has been refined over the years: as the atypical forms subsist near to the classical form (Hagberg & Gillberg, 1993), the "Rett Complex" terminology has been introduced.<ref>{{Cite journal |last=Gillberg |first=d. |year=1997 |title=Communication in Rett syndrome complex |journal=[[European Child & Adolescent Psychiatry]] |volume=6 |issue=Suppl 1 |pages=21–2 |pmid=9452914}}</ref><ref>{{Cite journal |last1=Zappella |first1=Michele |last2=Gillberg |first2=Christopher |last3=Ehlers |first3=Stephan |s2cid=22152062 |year=1998 |title=The preserved speech variant: A subgroup of the Rett complex: A clinical report of 30 cases |journal=Journal of Autism and Developmental Disorders |volume=28 |issue=6 |pages=519–26 |doi=10.1023/A:1026052128305 |pmid=9932238}}</ref>