Wrodzone zespoły miasteniczne

Wrodzone zespoły miasteniczne
Objawy

Wrodzone zespoły miasteniczne (CMS) to heterogenna grupa genetycznie uwarunkowanych zaburzeń przewodnictwa nerwowo-mięśniowego, charakteryzujących się męczliwym osłabieniem mięśni szkieletowych, najczęściej ujawniającym się w okresie noworodkowym lub wczesnego dzieciństwa. Dominującymi objawami są ptoza, osłabienie mięśni okoruchowych, opuszkowych oraz kończyn, trudności w żuciu, połykaniu i mowie, a także zaburzenia oddychania, które mogą prowadzić do epizodów bezdechu trwających od 30 sekund do ponad 30 minut (średnio około 2 minut). W ciężkich przypadkach obserwuje się także artrogrypozę, opóźnienie rozwoju motorycznego oraz deformacje kręgosłupa. Przebieg choroby jest zmienny, od łagodnych postaci z niewielką nietolerancją wysiłku do ciężkich, zagrażających życiu epizodów niewydolności oddechowej, szczególnie w typie CMS z epizodycznym bezdechem (CMS-EA). Warto podkreślić, że objawy mogą ulegać poprawie z wiekiem, zwłaszcza epizody bezdechu, które ustępują średnio w wieku 2 lat i 5 miesięcy.

Wprowadzenie do wrodzonych zespołów miastenicznych

Wrodzone zespoły miasteniczne (ang. Congenital Myasthenic Syndromes, CMS) stanowią heterogenną grupę rzadkich dziedzicznych schorzeń wynikających ze zmian genetycznych, które prowadzą do zaburzeń przewodnictwa nerwowo-mięśniowego w obrębie złącza nerwowo-mięśniowego. Charakterystyczną cechą tych chorób jest osłabienie mięśni, które nasila się podczas wysiłku fizycznego. W przeciwieństwie do miastenii nabytej (autoimmunologicznej), wrodzone zespoły miasteniczne są spowodowane mutacjami genetycznymi wpływającymi na strukturę lub funkcję białek złącza nerwowo-mięśniowego, a nie nieprawidłową odpowiedzią immunologiczną.¹²

Wrodzone zespoły miasteniczne najczęściej diagnozowane są przy urodzeniu lub we wczesnym dzieciństwie, choć w przypadku łagodnych objawów rozpoznanie może nastąpić w późniejszym dzieciństwie, a rzadko nawet w okresie dorosłości. Choroba ma charakter przewlekły i zazwyczaj towarzyszy pacjentowi przez całe życie.³⁴

Główne objawy: osłabianie mięśni i męczliwość

Podstawowym objawem występującym we wszystkich typach wrodzonych zespołów miastenicznych jest osłabienie mięśni, które nasila się wraz z aktywnością fizyczną i może ulegać poprawie po odpoczynku. Dotyczyć może wszystkich mięśni szkieletowych, jednak najczęściej zajmuje mięśnie odpowiedzialne za ruchy gałek ocznych i powiek oraz mięśnie żucia i połykania.⁵⁶

Dysfunkcja mięśni może prowadzić do różnorodnych objawów, w tym:⁷⁸

Opadania powiek (ptoza) i zaburzeń kontroli ruchów gałek ocznych, często z podwójnym widzeniem
Trudności w żuciu i połykaniu
Osłabienia mięśni twarzy
Słabego płaczu (u niemowląt)
Zaburzeń mowy (mowa nosowa lub niewyraźna)
Opóźnienia w rozwoju umiejętności motorycznych jak raczkowanie i chodzenie
Opóźnionego rozwoju sprawności nadgarstka, dłoni i palców (np. trudności z czynnościami jak mycie zębów czy czesanie włosów)
Trudności w utrzymaniu głowy w pozycji wyprostowanej
Problemów z oddychaniem (duszność, krótkie przerwy w oddychaniu), które mogą nasilać się podczas infekcji, gorączki lub stresu

Objawy u noworodków i niemowląt

Wrodzone zespoły miasteniczne najczęściej ujawniają się już w okresie noworodkowym lub w pierwszych miesiącach życia. U niemowląt obserwuje się:⁹¹⁰

Niewydolność oddechową z nagłym bezdechem i sinicą
Trudności w karmieniu
Słaby odruch ssania i płacz
Epizody krztuszenia się
Stridor (świszczący oddech)
Opadanie powiek
Uogólnione osłabienie mięśniowe

W przypadku ciężkiego przebiegu choroby, już w okresie płodowym może dochodzić do zmniejszonej ruchliwości płodu, co może prowadzić do przykurczów stawów przy urodzeniu (artrogrypozy) z powodu braku ruchów płodu w macicy.¹¹¹²

Objawy u dzieci i młodzieży

U dzieci z wrodzonym zespołem miastenicznym można zaobserwować:¹³¹⁴

Opóźnienie w osiąganiu kamieni milowych rozwoju motorycznego (siadanie, raczkowanie, chodzenie)
Nieprawidłową męczliwość mięśni – trudności w bieganiu czy wchodzeniu po schodach
Szybkie męczenie się podczas aktywności fizycznej
Trudności w nadążaniu za rówieśnikami w aktywnościach fizycznych
Opadanie powiek (ptoza) o stałym lub zmiennym nasileniu
Zaburzenia ruchów gałek ocznych

Z biegiem czasu u niektórych pacjentów może dochodzić do zmniejszenia masy mięśniowej oraz rozwoju deformacji kręgosłupa.¹⁵¹⁶

Objawy oddechowe i bezdech

Szczególnie niebezpiecznymi objawami wrodzonych zespołów miastenicznych są zaburzenia oddychania. W niektórych typach CMS, zwłaszcza w zespole CMS z epizodycznym bezdechem (CMS-EA), mogą występować nagłe epizody zatrzymania oddechu (bezdechu), które mogą zagrażać życiu.¹⁷

Epizody bezdechu często pojawiają się w pierwszych godzinach po urodzeniu (26% przypadków) lub w pierwszych 4 tygodniach życia (26% przypadków). Czas trwania takich epizodów waha się od 30 sekund do ponad 30 minut, a średni czas typowego epizodu wynosi około 2 minuty. Podczas epizodów bezdechu zwykle nasilają się inne objawy miasteniczne, takie jak wzmożona hipotonia, osłabienie opuszkowo-rdzeniowe i ptoza.¹⁸

Objawy oddechowe mogą nasilać się podczas infekcji, gorączki lub stresu. Słabe mięśnie oddechowe mogą prowadzić do częstych infekcji dróg oddechowych oraz nocnej hipowentylacji (płytkiego oddychania w nocy). Problemy z oddychaniem w nocy mogą powodować senność w ciągu dnia, poranne bóle głowy i nudności, słaby apetyt i utratę wagi.¹⁹

Zaburzenia mowy i połykania

Osłabienie mięśni może prowadzić do trudności z mową i połykaniem. Pacjenci mogą mieć mowę nosową i trudności z wyraźnym wypowiadaniem słów. Zaburzenia połykania mogą utrudniać bezpieczne jedzenie i picie, prowadząc do krztuszenia się podczas posiłków i uczucia, że pokarm utknął w gardle lub klatce piersiowej. Jeśli objawy pojawiają się przy urodzeniu, niemowlęta mogą mieć słaby odruch ssania i płaczu, co utrudnia karmienie.²⁰²¹

Ograniczenia ruchomości i przykurcze

U osób z wrodzonymi zespołami miastenicznymi może występować znaczna sztywność stawów (przykurcze). Jest to efekt zaciskania się ścięgien mięśniowych, co ogranicza zakres ruchu ramion i nóg, utrudniając wykonywanie precyzyjnych ruchów (koordynację małych mięśni palców i dłoni podczas czynności takich jak mycie zębów).²²

Przebieg choroby i zmienność objawów

Ciężkość i przebieg wrodzonych zespołów miastenicznych są bardzo zróżnicowane i zależą od podstawowego defektu genetycznego. Objawy mogą być niezwykle różnorodne – od łagodnego osłabienia (np. niewielka nietolerancja wysiłku) do postępującego, znacznego osłabienia powodującego niepełnosprawność.²³²⁴

W niektórych podtypach CMS objawy miasteniczne mogą być łagodne, ale mogą występować nagłe, ciężkie zaostrzenia osłabienia lub nawet nagłe epizody niewydolności oddechowej, które mogą być wywołane przez gorączkę, infekcje lub stres.²⁵

U niektórych pacjentów obserwuje się stopniową poprawę objawów wraz z wiekiem, szczególnie w przypadku epizodów bezdechu. W większości przypadków CMS-EA występuje tendencja do całkowitej remisji epizodów bezdechu z wiekiem (średni wiek ustąpienia objawów wynosi 2 lata i 5 miesięcy).²⁶

Nasilenie objawów w zależności od wieku wystąpienia

Ogólnie rzecz biorąc, im wcześniej pojawiają się objawy, tym poważniejszy jest prawdopodobny przebieg choroby. Przypadki z początkiem w wieku niemowlęcym są zazwyczaj cięższe niż te, które pojawiają się w późniejszym dzieciństwie lub dorosłości.²⁷²⁸

Osoby, u których objawy pojawiają się później w dzieciństwie, prezentują zazwyczaj nieprawidłową męczliwość mięśni, trudności w bieganiu lub wchodzeniu po schodach. Mogą mieć opóźnione kamienie milowe rozwoju motorycznego. U tych pacjentów często występuje opadanie powiek o zmiennym nasileniu oraz stałe lub zmienne osłabienie mięśni okoruchowych.²⁹

Wpływ choroby na jakość życia i długość życia

Wrodzone zespoły miasteniczne mogą mieć różny wpływ na długość życia pacjenta. W przypadku łagodnych objawów, CMS nie będzie miało znaczącego wpływu na ogólny stan zdrowia. Jednak CMS może wpłynąć na długość życia, jeśli objawy dotyczą mięśni, które regulują oddychanie.³⁰

U osób z ciężkimi postaciami choroby występują trudności oddechowe od wczesnego dzieciństwa, które powinny być regularnie monitorowane. Jeśli problemy oddechowe nie są odpowiednio kontrolowane, mogą prowadzić do kryzysu oddechowego i stać się zagrożeniem dla życia.³¹

Objawy specyficzne dla różnych podtypów CMS

W zależności od rodzaju wrodzonego zespołu miastenicznego, mogą występować dodatkowe objawy:³²³³

Deformacje szkieletowe, takie jak deformacje stawów, kręgosłupa lub stóp
Nietypowe cechy twarzy, jak wąska szczęka lub szeroko rozstawione oczy
Utrata słuchu
Osłabienie, drętwienie i ból, zwykle w rękach i stopach
Napady padaczkowe
Problemy z nerkami
Upośledzenie funkcji poznawczych (rzadko)

Przedsynaptyczny CMS

Przedsynaptyczny CMS często objawia się jako CMS z epizodycznym bezdechem (CMS-EA). Rozpoczyna się w okresie niemowlęcym i powoduje osłabienie mięśni ocznych, które może prowadzić do opadania powiek (ptozy). Powoduje również osłabienie opuszkowe (nazwane od nerwów, które pochodzą z opuszkowej części pnia mózgu), utrudniając mówienie, żucie, połykanie i utrzymanie głowy w górze. Ten typ charakteryzuje się również epizodami bezdechu, czyli czasowym zatrzymaniem oddychania.³⁴

Postsynaptyczny CMS

Postsynaptyczny CMS (niedobór receptorów ACh, szybkokanałowy CMS) ma objawy od łagodnych do skrajnych. U niemowląt może powodować ciężkie osłabienie, problemy z karmieniem i oddychaniem oraz opóźnione kamienie milowe motoryczne (siadanie, raczkowanie i chodzenie). Przypadki z początkiem w dzieciństwie i dorosłości często powodują ptozę i zmęczenie, ale zwykle nie przeszkadzają w codziennym życiu.³⁵

Postsynaptyczny CMS (wolnokanałowy CMS) powoduje skrajne osłabienie w przypadkach rozpoczynających się w niemowlęctwie, często prowadząc do utraty mobilności i problemów oddechowych w okresie dojrzewania. Przypadki z początkiem w wieku dorosłym mogą nie powodować niepełnosprawności.³⁶

Synaptyczny CMS

Synaptyczny CMS może powodować skrajne osłabienie z trudnościami w karmieniu i oddychaniu od urodzenia lub wczesnego dzieciństwa. Osłabienie powoduje również opóźnione kamienie milowe motoryczne i często prowadzi do zmniejszonej mobilności i skoliozy (skrzywienia kręgosłupa).³⁷

Ciąża i wrodzone zespoły miasteniczne

Ciąża może pogorszyć objawy wrodzonych zespołów miastenicznych, dlatego wymagana jest ścisła kontrola podczas ciąży i po porodzie.³⁸³⁹

Podsumowanie kluczowych objawów

Wrodzone zespoły miasteniczne charakteryzują się:⁴⁰⁴¹

Męczliwym osłabieniem mięśni szkieletowych (np. mięśni oczu, opuszkowych, kończyn)
Początkiem objawów przy urodzeniu lub krótko po nim, lub we wczesnym dzieciństwie; rzadko początek może nastąpić w drugiej lub trzeciej dekadzie życia
Bardzo zmiennym przebiegiem i nasileniem objawów – od łagodnych do postępujących, powodujących niepełnosprawność
Możliwością nagłych, ciężkich zaostrzeń osłabienia lub epizodów niewydolności oddechowej, które mogą być wywołane przez gorączkę, infekcje lub stres

Precyzyjne rozpoznanie typu wrodzonego zespołu miastenicznego jest kluczowe, ponieważ odpowiednie leczenie może znacząco złagodzić objawy i poprawić jakość życia pacjentów.⁴²

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Materiały źródłowe

#1 Congenital myasthenic syndromes – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/symptoms-causes/syc-20354754
Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical activity. Any muscles used for movement can be affected, including muscles that control speaking, chewing and swallowing, seeing and blinking, breathing, and walking. […] Congenital myasthenic syndromes are usually identified at birth or early childhood and are lifelong conditions. […] Depending on the type of congenital myasthenic syndrome, the severity of signs and symptoms vary greatly, from minor weakness to the inability to move. Some symptoms can be life-threatening. […] Common to all congenital myasthenic syndromes is muscle weakness that worsens with physical activity. Any muscles used for movement can be affected, but the most commonly affected muscles are those that control movement of the eyelids and eyes and chewing and swallowing.
#2 Congenital Myasthenic Syndrome (CMS): Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/congenital-myasthenic-syndrome
Congenital myasthenic syndrome is a group of conditions that cause muscle weakness that gets worse with physical activity (exertion). Symptoms can be mild or severe. Severe cases may be life-threatening, especially if CMS affects the muscles that help you breathe. […] The signs and symptoms of congenital myasthenic syndrome vary based on type but could include: Muscle fatigue and weakness triggered by physical activity. Limited or a lack of muscle regulation. Droopy eyelids, double vision or a lazy eye. Difficulty talking or swallowing. […] Most congenital myasthenic syndrome symptoms begin in early childhood. A sign that your child might have CMS is delayed motor skills development (like crawling and walking). Some symptoms of CMS start later, for example, during adolescence or adulthood.
#3 Health Information Library | Rumah Sakit Pusat Pertamina
https://rspp.co.id/dcontent.html?id=CON-20209446&n=Congenital%20myasthenic%20syndromes
Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical activity. Any muscles used for movement can be affected, including muscles that control speaking, chewing and swallowing, seeing and blinking, breathing, and walking. […] Congenital myasthenic syndromes are usually identified at birth or early childhood and are lifelong conditions. […] Congenital myasthenic syndromes are typically identified at birth. But if signs and symptoms are mild, the condition may not be identified until childhood, or rarely, early adulthood. […] Depending on the type of congenital myasthenic syndrome, the severity of signs and symptoms vary greatly, from minor weakness to the inability to move. Some symptoms can be life-threatening.
#4 Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes
Depending on the type, symptoms of CMS vary from mild to severe, but generally include weakness, fatigue and ptosis (droopy eyelids). The earlier the onset of CMS, the more severe the symptoms are likely to be. […] As its name implies, CMS usually has a congenital (at or near birth) onset, but it can manifest in children and even in adults. Later-onset cases tend to be milder.
#5 Congenital myasthenic syndromes // Middlesex Health
https://middlesexhealth.org/learning-center/diseases-and-conditions/congenital-myasthenic-syndromes
Congenital myasthenic syndromes are typically identified at birth. But if signs and symptoms are mild, the condition may not be identified until childhood, or rarely, early adulthood. […] Depending on the type of congenital myasthenic syndrome, the severity of signs and symptoms vary greatly, from minor weakness to the inability to move. Some symptoms can be life-threatening. […] Common to all congenital myasthenic syndromes is muscle weakness that worsens with physical activity. Any muscles used for movement can be affected, but the most commonly affected muscles are those that control movement of the eyelids and eyes and chewing and swallowing. […] During infancy and early childhood, progressive loss of essential voluntary muscle activity occurs with muscle use. Impaired muscle weakness can result in: Droopy eyelids and poor eye control, often with double vision. Difficulty chewing and swallowing. Weakness of facial muscles. Weak cry. Slurring or nasal speech. Delayed crawling and walking. Delayed development of wrist, hand and finger skills, such as brushing teeth or combing hair. Trouble supporting the head in an upright position. Problems breathing, such as feeling short of breath and having short pauses in breathing, sometimes worsened by infection, fever or stress.
#6 Congenital myasthenic syndromes – Hancock Health
https://www.hancockhealth.org/mayo-health-library/congenital-myasthenic-syndromes/
Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical activity. Any muscles used for movement can be affected, including muscles that control speaking, chewing and swallowing, seeing and blinking, breathing, and walking. […] Congenital myasthenic syndromes are usually identified at birth or early childhood and are lifelong conditions. […] Depending on the type of congenital myasthenic syndrome, the severity of signs and symptoms vary greatly, from minor weakness to the inability to move. Some symptoms can be life-threatening. […] Common to all congenital myasthenic syndromes is muscle weakness that worsens with physical activity. Any muscles used for movement can be affected, but the most commonly affected muscles are those that control movement of the eyelids and eyes and chewing and swallowing.
#7 Congenital myasthenic syndromes – Symptoms and causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/symptoms-causes/syc-20354754
During infancy and early childhood, progressive loss of essential voluntary muscle activity occurs with muscle use. Impaired muscle weakness can result in: Droopy eyelids and poor eye control, often with double vision. Difficulty chewing and swallowing. Weakness of facial muscles. Weak cry. Slurring or nasal speech. Delayed crawling and walking. Delayed development of wrist, hand and finger skills, such as brushing teeth or combing hair. Trouble supporting the head in an upright position. Problems breathing, such as feeling short of breath and having short pauses in breathing, sometimes worsened by infection, fever or stress. […] Depending on the type of congenital myasthenic syndrome, other signs and symptoms can include: Skeletal deformities, such as joint, spine or foot deformities. Unusual facial features, such as narrow jaw or wide-set eyes. Hearing loss. Weakness, numbness and pain, usually in hands and feet. Seizures. Kidney problems. Cognitive impairment, rarely.
#8 Health Information Library | Rumah Sakit Pusat Pertamina
https://rspp.co.id/dcontent.html?id=CON-20209446&n=Congenital%20myasthenic%20syndromes
Common to all congenital myasthenic syndromes is muscle weakness that worsens with physical activity. Any muscles used for movement can be affected, but the most commonly affected muscles are those that control movement of the eyelids and eyes and chewing and swallowing. […] During infancy and early childhood, progressive loss of essential voluntary muscle activity occurs with muscle use. Impaired muscle weakness can result in: Droopy eyelids and poor eye control, often with double vision. Difficulty chewing and swallowing. Weakness of facial muscles. Weak cry. Slurring or nasal speech. Delayed crawling and walking. Delayed development of wrist, hand and finger skills, such as brushing teeth or combing hair. Trouble supporting the head in an upright position. Problems breathing, such as feeling short of breath and having short pauses in breathing, sometimes worsened by infection, fever or stress.
#9 Congenital Myasthenic Syndromes | CheckRare
https://checkrare.com/congenital-myasthenic-syndromes/
Congenital myasthenic syndromes (CMS) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. […] Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. […] The first myasthenic symptoms occur in general early in life, usually in the first two years. […] CMS is limited to weakness of the skeletal muscles. […] Some myasthenic symptoms are present at birth: Respiratory insufficiency with sudden apnea and cyanosis are common findings in neonates. […] Individuals with onset later in childhood show abnormal muscle fatigability, with difficulty in running or climbing stairs: Motor milestones may be delayed.
#10 Congenital Myasthenic Syndrome – CheckOrphan
https://checkorphan.org/video/congenital-myasthenic-syndrome/
Congenital myasthenic syndromes (CMS) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. […] Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. […] Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
#11 Hometown Highlights: Congenital Myasthenic Syndromes
https://practicalneurology.com/articles/2019-feb/hometown-highlights-congenital-myasthenic-syndromes
With careful diagnosis, treatment can improve symptoms of congenital myasthenic syndromes. Although there are some congenital myasthenic syndromes (CMS) that have later onset, most present in early infancy or childhood with fatigable weakness of the oculobulbar and limb muscles. In some cases, weakness can be restricted to select muscles. In utero, there may be hypomotility or akinesia. During the neonatal period, infants with CMS may have poor cry and suck, with stridor, choking, and recurrent apnea. Ptosis, hypotonia, and arthrogryposis also occur, and symptoms worsen with activity. These children typically have delayed motor milestones and seldom learn to run or climb stairs well. They fatigue easily and may have difficulty keeping up with their peers in physical activity. Reduced muscle bulk and spinal deformities can be seen.
#12 Congenital Myasthenic Syndromes (CMS) – Rare Awareness Rare Education
https://rareportal.org.au/rare-disease/congenital-myasthenic-syndromes-cms/
Congenital Myasthenic Syndromes (CMS) are characterised by muscle weakness which worsens with physical activity and mostly affects the muscles of the face, neck, throat, eyes and limbs. […] CMS typically presents at birth or in early childhood, usually within the first decade of life. Symptoms range from mild to severe muscle weakness and may worsen over time or only occur periodically. […] Congenital myasthenic syndromes (CMS) are characterised by fatiguable weakness (weakness that worsens with physical activity and may improve temporarily with rest), mainly in the skeletal muscles such as muscles of the face, neck, throat, eyes and limbs, at birth or in early childhood. […] Other symptoms may present at birth, including feeding and respiratory difficulties, poor suck and cry, choking spells, noisy breathing (stridor) and drooping eyelid (ptosis). Some babies may have joint stiffness (contractures or arthrogryposis multiplex congenita) due to lack of movement in utero. There may also be delayed development of motor skills during childhood. […] Degeneration of muscle tissue (atrophy) is usually not observed with CMS, except for a specific CMS that is caused by defects in the GMPPB gene (GMPPB-related CMS).
#13 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) has symptoms ranging from mild to extreme. In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually dont interfere with daily living. […] Postsynaptic CMS (slow-channel CMS) causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling. […] Synaptic CMS can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
#14 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK
https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/
Symptoms of congenital myasthenic syndromes usually begin at birth or in early childhood, but in some cases could begin in early adulthood. In general, the earlier the symptoms begin, the more severe they are likely to be. Some symptoms can be life-threatening. […] All types of CMS cause muscle weakness that worsens with activity. This may affect specific muscle groups or be spread throughout all muscles in the body. In infants, CMS can cause delays in achieving motor milestones such as sitting, crawling, and walking. People may struggle to walk long distances, climb stairs, and may be more likely to fall. […] CMS can cause droopy eyelids (ptosis), where the muscles in one or both eyelids have weakened and droop. This can affect vision, as the eyelid begins to cover the pupil of the eyes. Weakness of the muscles around the eyeball can mean that the eye moves less, and more head movement is needed to look around. This can sometimes cause double vision (diplopia) which can have an impact on day-to-day activities though this is rare.
#15 Hometown Highlights: Congenital Myasthenic Syndromes
https://practicalneurology.com/diseases-diagnoses/child-neurology/hometown-highlights-congenital-myasthenic-syndromes/30130/
Although there are some congenital myasthenic syndromes (CMS) that have later onset, most present in early infancy or childhood with fatigable weakness of the oculobulbar and limb muscles. In some cases, weakness can be restricted to select muscles. In utero, there may be hypomotility or akinesia. During the neonatal period, infants with CMS may have poor cry and suck, with stridor, choking, and recurrent apnea. Ptosis, hypotonia, and arthrogryposis also occur, and symptoms worsen with activity. These children typically have delayed motor milestones and seldom learn to run or climb stairs well. They fatigue easily and may have difficulty keeping up with their peers in physical activity. Reduced muscle bulk and spinal deformities can be seen. […] The course of disease is progressive with spontaneous intermittent worsening.
#16 Congenital Myasthenic Syndromes (CMS) – Rare Awareness Rare Education
https://rareportal.org.au/rare-disease/congenital-myasthenic-syndromes-cms/
Congenital Myasthenic Syndromes (CMS) are characterised by muscle weakness which worsens with physical activity and mostly affects the muscles of the face, neck, throat, eyes and limbs. […] CMS typically presents at birth or in early childhood, usually within the first decade of life. Symptoms range from mild to severe muscle weakness and may worsen over time or only occur periodically. […] Congenital myasthenic syndromes (CMS) are characterised by fatiguable weakness (weakness that worsens with physical activity and may improve temporarily with rest), mainly in the skeletal muscles such as muscles of the face, neck, throat, eyes and limbs, at birth or in early childhood. […] Other symptoms may present at birth, including feeding and respiratory difficulties, poor suck and cry, choking spells, noisy breathing (stridor) and drooping eyelid (ptosis). Some babies may have joint stiffness (contractures or arthrogryposis multiplex congenita) due to lack of movement in utero. There may also be delayed development of motor skills during childhood. […] Degeneration of muscle tissue (atrophy) is usually not observed with CMS, except for a specific CMS that is caused by defects in the GMPPB gene (GMPPB-related CMS).
#17
https://link.springer.com/article/10.1007/s00415-017-8689-3
Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy. The underlying mechanisms for sudden and recurrent episodes of respiratory arrest in these patients are unclear. Most patients manifested intermittent apnoea in the first 4 months of life (74%, n= 14). A degree of clinical improvement with medication was observed in most patients (74%, n= 14), but the majority of cases also showed a tendency towards complete remission of apnoeic events with age (mean age of resolution 2 years 5 months). Signs of impaired neuromuscular transmission were detected on neurophysiology studies in 79% (n = 15) of cases, but in six cases, this was only apparent following specific neurophysiological testing protocols (prolonged high-frequency stimulation).
#18
https://link.springer.com/article/10.1007/s00415-017-8689-3
Age of onset of EA was variable. Most patients had their first apnoea in the hours following birth (n= 5, 26%) or in the first 4 weeks of life (n= 5, 26%). For four cases (21%), the first apnoeic event occurred between the age of 14 months, and four cases developed EA between 4 and 12 months of age. In one case, EA did not occur until the age of 18 months. […] During apnoeic episodes, myasthenic features typically worsened, with worsening of hypotonia, bulbar weakness and ptosis reported in 14, 6 and 4 cases, respectively. Approximate duration of events ranged from 30 s to over 30 min (persisting until the patient was intubated and ventilated, and resulting in permanent brain damage), but mean duration of a typical event was 2 min. […] However, overall progressive improvement and tendency towards resolution of apnoeic episodes was reported in the majority of cases. For 11 cases there was complete remission of apnoeas (mean age of resolution 2 and 5 months). A further five cases showed tendency towards remission but still experienced apnoeas during infections. There was no genotype-phenotype correlation between cases who had remission of EA and those who still experienced apnoeas.
#19 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK
https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/
People with CMS may be born with, or later develop, significant stiffness in the joints (contractures). This is where the muscle tendons tighten up and limit the range of movement in the arms and legs, which can make fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth) challenging. […] In some types of CMS, weak breathing muscles can cause respiratory issues from an early age, which should be regularly monitored. If respiratory issues aren’t properly managed, they can lead to respiratory crisis and become life-threatening. Weak breathing muscles can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Overnight breathing problems may cause daytime sleepiness, morning headaches and nausea, poor appetite, and weight loss.
#20 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK
https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/
People may have difficulties with speech and swallowing because of muscle weakness. This can cause nasal speech and make it harder to pronounce words clearly. […] Swallowing can be affected and make it difficult to eat and drink safely. This can lead to coughing and choking during meals and feeling like food is stuck in the throat or chest. If symptoms start at birth, babies may have a weak suck and cry, making feeding difficult.
#21 Congenital myasthenic syndrome | Myasthenia Gravis NewsEnvelope icon
https://myastheniagravisnews.com/congenital-myasthenia/
CMS often presents at birth or soon after a baby is born. Early symptoms of the disease can include: difficulty breathing or bouts of apnea, or periods when breathing stops, which can lead to symptoms like cyanosis, marked by blue skin discoloration; stridor, or a high-pitched sound during breathing that occurs due to a narrowing of the airways; trouble feeding; poor suck and cry; choking spells; ptosis, or eyelid droopiness; contractures, or stiff, immobile joints that are caused by lack of fetal movement in the womb; ocular, facial, or bulbar weakness, which refers to signs of weakness in the muscles of the face and neck; other generalized signs of muscle weakness, such as moving around less than usual. […] In some cases, CMS symptoms donât reveal themselves until later in childhood or even early adulthood. When CMS symptoms arise later on in life, they often follow a limb-girdle pattern. That means that weakness primarily affects muscles close to the torso, such as those in the shoulders and hips. Symptoms of CMS in older individuals can include: delays in reaching typical motor milestones, such holding the head upright, sitting, crawling, or walking; delayed development of fine motor skills required for using utensils or brushing teeth; ptosis and poor eye control, often leading to double vision; nasal speech; trouble breathing; difficulty swallowing, chewing, and coughing; deformities of the spine, joints, and feet; muscle atrophy, or wasting.
#22 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK
https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/
People with CMS may be born with, or later develop, significant stiffness in the joints (contractures). This is where the muscle tendons tighten up and limit the range of movement in the arms and legs, which can make fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth) challenging. […] In some types of CMS, weak breathing muscles can cause respiratory issues from an early age, which should be regularly monitored. If respiratory issues aren’t properly managed, they can lead to respiratory crisis and become life-threatening. Weak breathing muscles can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Overnight breathing problems may cause daytime sleepiness, morning headaches and nausea, poor appetite, and weight loss.
#23 Congenital Myasthenic Syndromes Overview – GeneReviewsÂ® – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK1168/
Prognosis. Severity and course of disease are highly variable and depend on the underlying genetic defect. Findings range from minor symptoms (e.g., mild exercise intolerance) to progressive disabling weakness. Minor myasthenic symptoms may be exacerbated by sudden onset of severe weakness or respiratory insufficiency precipitated by fever, infections, or excitement, especially in individuals with CMS with episodic apnea or endplate rapsyn deficiency.
#24 Congenital Myasthenic Syndromes | CheckRare
https://checkrare.com/congenital-myasthenic-syndromes/
Affected individuals present with fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness. […] In addition, facial and bulbar weakness with nasal speech and difficulties in coughing and swallowing may be present. […] Severity and course of disease are highly variable, ranging from minor symptoms (e.g., mild exercise intolerance) to progressive disabling weakness. […] In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement.
#25 Congenital Myasthenic Syndromes Overview – GeneReviewsÂ® – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK1168/
Prognosis. Severity and course of disease are highly variable and depend on the underlying genetic defect. Findings range from minor symptoms (e.g., mild exercise intolerance) to progressive disabling weakness. Minor myasthenic symptoms may be exacerbated by sudden onset of severe weakness or respiratory insufficiency precipitated by fever, infections, or excitement, especially in individuals with CMS with episodic apnea or endplate rapsyn deficiency.
#26
https://link.springer.com/article/10.1007/s00415-017-8689-3
Age of onset of EA was variable. Most patients had their first apnoea in the hours following birth (n= 5, 26%) or in the first 4 weeks of life (n= 5, 26%). For four cases (21%), the first apnoeic event occurred between the age of 14 months, and four cases developed EA between 4 and 12 months of age. In one case, EA did not occur until the age of 18 months. […] During apnoeic episodes, myasthenic features typically worsened, with worsening of hypotonia, bulbar weakness and ptosis reported in 14, 6 and 4 cases, respectively. Approximate duration of events ranged from 30 s to over 30 min (persisting until the patient was intubated and ventilated, and resulting in permanent brain damage), but mean duration of a typical event was 2 min. […] However, overall progressive improvement and tendency towards resolution of apnoeic episodes was reported in the majority of cases. For 11 cases there was complete remission of apnoeas (mean age of resolution 2 and 5 months). A further five cases showed tendency towards remission but still experienced apnoeas during infections. There was no genotype-phenotype correlation between cases who had remission of EA and those who still experienced apnoeas.
#27 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
As its name implies, congenital myasthenic syndromes (CMS) usually have a congenital (at or near birth) onset, but the disease can manifest in children and even in adults. The different types vary in the kind and degree of symptoms, but generally speaking, the earlier the symptoms appear, the more pronounced the disease is likely to be. […] Presynaptic CMS commonly appears as CMS with episodic apnea (CMS-EA). It has its onset in infancy and causes ocular weakness weakness in muscles controlling the eyes which can cause droopy eyelids (ptosis). It also causes bulbar weakness (named for the nerves that originate from the bulblike part of the brainstem) making it difficult to talk, chew, swallow and hold up the head. This type is also characterized by episodes of apnea, a temporary cessation of breathing.
#28 Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes
Depending on the type, symptoms of CMS vary from mild to severe, but generally include weakness, fatigue and ptosis (droopy eyelids). The earlier the onset of CMS, the more severe the symptoms are likely to be. […] As its name implies, CMS usually has a congenital (at or near birth) onset, but it can manifest in children and even in adults. Later-onset cases tend to be milder.
#29 Congenital myasthenic syndrome (CMS) – Baby Detect
https://babydetect.com/en/congenital-myasthenic-syndrome-cms-dok7-rapsn-gfpt1-achre-colq-chat-agrn-alg2-alg14-chrna1-chrnb1-chrnd-gmppb-col13a1-dpagt1-lrp4-musk-myo9a-prepl-plec-slc25a1-slc5a7/
Some myasthenic symptoms are present at birth. Respiratory insufficiency with sudden, episodic apnea and cyanosis are common findings in neonates. […] Other major findings in the neonatal period may include feeding difficulties, poor suck, and cry, choking spells, eyelid ptosis, and facial, bulbar, and generalized weakness. […] Individuals with onset later in childhood show abnormal muscle fatigability, with difficulty in running or climbing stairs. Motor milestones may be delayed. Affected individuals present with fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness. […] Spinal deformity or muscle atrophy may occur.
#30 Congenital Myasthenic Syndrome (CMS): Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/congenital-myasthenic-syndrome
Congenital myasthenic syndrome symptoms range from mild to severe. It may have very little effect on your life, while others may experience life-threatening symptoms like breathing difficulties. […] Congenital myasthenic syndrome may or may not affect your life expectancy. If you have mild symptoms, CMS won’t have a major effect on your overall health. CMS can impact your life expectancy if symptoms affect the muscles that regulate your breathing.
#31 Congenital myasthenic syndromes (CMS) – Muscular Dystrophy UK
https://www.musculardystrophyuk.org/conditions/a-z/congenital-myasthenic-syndrome-cms/
People with CMS may be born with, or later develop, significant stiffness in the joints (contractures). This is where the muscle tendons tighten up and limit the range of movement in the arms and legs, which can make fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth) challenging. […] In some types of CMS, weak breathing muscles can cause respiratory issues from an early age, which should be regularly monitored. If respiratory issues aren’t properly managed, they can lead to respiratory crisis and become life-threatening. Weak breathing muscles can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Overnight breathing problems may cause daytime sleepiness, morning headaches and nausea, poor appetite, and weight loss.
#32 Mayo Clinic Health Library – Congenital myasthenic syndromes | Swiss Medical Network
https://www.swissmedical.net/en/healtcare-library/con-20209446
Depending on the type of congenital myasthenic syndrome, other signs and symptoms can include: Skeletal deformities, such as joint, spine or foot deformities. Unusual facial features, such as narrow jaw or wide-set eyes. Hearing loss. Weakness, numbness and pain, usually in hands and feet. Seizures. Kidney problems. Cognitive impairment, rarely.
#33 Congenital myasthenic syndromes // Middlesex Health
https://middlesexhealth.org/learning-center/diseases-and-conditions/congenital-myasthenic-syndromes
Depending on the type of congenital myasthenic syndrome, other signs and symptoms can include: Skeletal deformities, such as joint, spine or foot deformities. Unusual facial features, such as narrow jaw or wide-set eyes. Hearing loss. Weakness, numbness and pain, usually in hands and feet. Seizures. Kidney problems. Cognitive impairment, rarely.
#34 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
As its name implies, congenital myasthenic syndromes (CMS) usually have a congenital (at or near birth) onset, but the disease can manifest in children and even in adults. The different types vary in the kind and degree of symptoms, but generally speaking, the earlier the symptoms appear, the more pronounced the disease is likely to be. […] Presynaptic CMS commonly appears as CMS with episodic apnea (CMS-EA). It has its onset in infancy and causes ocular weakness weakness in muscles controlling the eyes which can cause droopy eyelids (ptosis). It also causes bulbar weakness (named for the nerves that originate from the bulblike part of the brainstem) making it difficult to talk, chew, swallow and hold up the head. This type is also characterized by episodes of apnea, a temporary cessation of breathing.
#35 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) has symptoms ranging from mild to extreme. In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually dont interfere with daily living. […] Postsynaptic CMS (slow-channel CMS) causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling. […] Synaptic CMS can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
#36 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) has symptoms ranging from mild to extreme. In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually dont interfere with daily living. […] Postsynaptic CMS (slow-channel CMS) causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling. […] Synaptic CMS can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
#37 Signs and Symptoms of Congenital Myasthenic Syndromes (CMS) – Diseases | Muscular Dystrophy Association
https://www.mda.org/disease/congenital-myasthenic-syndromes/signs-and-symptoms
Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) has symptoms ranging from mild to extreme. In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually dont interfere with daily living. […] Postsynaptic CMS (slow-channel CMS) causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling. […] Synaptic CMS can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
#38 Congenital myasthenic syndromes – Diagnosis and treatment – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/congenital-myasthenic-syndrome/diagnosis-treatment/drc-20557730
Your doctor will do a physical examination including a neurological exam and review symptoms and medical history to check for signs of a congenital myasthenic syndrome. […] The following tests can help diagnose a congenital myasthenic syndrome and determine how severe the disorder is. […] Rarely, some children with mild congenital myasthenic syndromes may not need treatment. […] Medications aren’t a cure, but they can improve muscle contraction and muscle strength in people with congenital myasthenic syndromes. […] Supportive treatments depend on the type and severity of the congenital myasthenic syndrome. […] Regular follow-up appointments with a team of medical professionals provides ongoing care and may help prevent certain complications. […] Pregnancy can worsen symptoms of congenital myasthenic syndromes, so close monitoring during and after pregnancy is required. […] Make an appointment with your doctor if you notice signs or symptoms common to congenital myasthenic syndromes.
#39 Congenital myasthenic syndromes – Hancock Health
https://www.hancockhealth.org/mayo-health-library/congenital-myasthenic-syndromes/
Regular follow-up appointments with a team of medical professionals provides ongoing care and may help prevent certain complications. Your health care team can link you with appropriate support for home, school or work. […] Pregnancy can worsen symptoms of congenital myasthenic syndromes, so close monitoring during and after pregnancy is required.
#40 Congenital Myasthenic Syndromes Overview – GeneReviewsÂ® – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK1168/
An individual with a congenital myasthenic syndrome (CMS) typically presents with a history of fatigable weakness involving ocular, bulbar, and limb muscles with onset at or shortly after birth or in early childhood, usually in the first two years. Rarely, onset is in the second to third decade of life. […] Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. […] Some myasthenic symptoms are present at birth. […] Respiratory insufficiency with sudden, episodic apnea and cyanosis are common findings in neonates. […] Individuals with onset later in childhood show abnormal muscle fatigability, with difficulty in running or climbing stairs.
#41
https://www.myaware.org/congenital-myasthenia
Congenital (hereditary) myasthenic syndrome (CMS) is a group of conditions characterised by fatigable muscle weakness, caused by an inherited disorder affecting the junction between the nerve and the muscle. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. […] Symptoms of CMS vary from person to person and fluctuate throughout the day and they can also overlap with other muscular disorders, although people with CMS may notice the following: […] Babies: Decreased movements of the baby inside the mother’s womb before birth, Weak suck and cry, Reduced movements, Difficulties in feeding and swallowing, Breathing difficulties. […] Children and adults: Late walking, May struggle with sport, exertion or activities of daily living, Difficulty performing repetitive movements, Frequent chest infections, Stiffness in fingers and wrists, Droopy eyelids, Double vision, Tendency to fall easily.
#42 Hometown Highlights: Congenital Myasthenic Syndromes
https://practicalneurology.com/articles/2019-feb/hometown-highlights-congenital-myasthenic-syndromes
Identifying the specific type of syndrome is critical as medications that help patients with certain syndromes may worsen the symptoms in other syndromes. […] Although CMS are disabling diseases, when correctly diagnosed, appropriate therapy can improve the symptoms of most patients with CMS. […] Patients with Dok7 myasthenia have early onset of disease as seen by decreased fetal movements and myasthenic symptoms in the neonatal period or early infancy. Myasthenic symptoms include proximal and distal limb and axial fatigable weakness, facial and eyelid weakness, and bulbar and respiratory symptoms. The course of disease is progressive with spontaneous intermittent worsening. […] Although CMS are disabling diseases, when correctly diagnosed, most CMS can be improved with appropriate therapy.