Summary: (1) Delayed psychomotor development, (2) Characteristic facies, (3) Abnormalities of the external genitalia, (4) Skeletal abnormalities, (5) Abnormal behaviour and posture: Putting his hand in the mouth to induce vomiting, looking upward at an angle, turning the palms upward, thrusting the chin forward, or making gestures that resemble choking, (6) Autistic symptoms: Difficulty maintaining eye contact, repetitive movements, (7) Gastrointestinal abnormalities: Gastroesophageal reflux, aerophagia, ileus, constipation, (8) Laboratory findings: Alpha thalassaemia (Presence of red blood cells containing golf ball-shaped inclusions stained with Brilliant Cresyl Blue in peripheral blood)
A. Mandatory symptoms/findings (＞90%)
1. male
2. Severe mental and motor developmental delay
3. Characteristic facies: Hypoplasia of the central facial region (upward-turned nostrils, thick lower lip, flat nasal bridge, triangular mouth, widely spaced incisors), microcephaly, low-set ears
B. Symptoms/findings frequently observed (50% or more)
Neonatal period: feeding difficulties (requiring tube feeding), hypotonia
Genital abnormalities: micropenis, cryptorchidism, small penis, female genitalia
Digestive system abnormalities: Aerophagia, vomiting, gastroesophageal reflux, constipation,ileus, excessive drooling
Skeletal abnormalities: tapered fingers, short fifth finger, flexion contractures of finger joints
Growth: short stature
Postural and motor abnormalities: putting hands in mouth to induce vomiting, sudden laughing fits, emotional outbursts
Autistic-like: avoiding eye contact, repetitive movements, e.x. finger rubbing (pill-rolling)
Posture: looking upward at an angle, tilting the chin upward with the palm of the hand, or making a gesture of tightening the neck, self-injury
C. Symptoms and findings frequently observed (50% or less)
Central nervous system: epilepsy, heart, cardiac malformations, kidney malformations, hypoplasia, etc.
Ophthalmology: cataracts, strabismus, etc.
Other: unexplained encephalopathy-like symptoms, periodically recurring episodes of complete refusal to eat, apnoea, cyanotic episodes, walking with bent knees and small steps, unique gait with kyphosis (in cases where walking was acquired), scoliosis, sleep disorders
[Laboratory findings]
1. Presence of red blood cells containing HbH inclusions stained with Brilliant Cresyl Blue: (Positive rate: approximately 80%) Even in positive cases, the positive rate may range from more than 40% of peripheral red blood cells to less than 1%. A negative result does not rule out this syndrome.
2. Brain MRI: No characteristic findings specific to this syndrome are observed. Structural abnormalities of the brain (brain atrophy, corpus callosum agenesis), white matter signal abnormalities, delayed myelination, leukoencephalopathy, and progressive brain atrophy have been reported.
3. Presence of ATRX gene mutations: A definitive diagnosis is made only when ATRX gene mutations are confirmed.
ATRX