A woman in the 21–25 age group with a de novo truncating ASH1L variant, lifelong developmental and language differences, moderate intellectual disability, autism-spectrum disorder, and substantial support needs. Her childhood records document a distinctive combination of auditory-language difficulty, severe visuomotor-integration weakness, low muscle tone, sensory-processing differences, and much stronger performance when tasks were quiet, predictable, and supported.
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Regulation, oral health, neurology, sleep, and cognition5 sections
Chapter 04Movement, pain, skin, dizziness, digestion, and hormones
18
Muscle tone, pain, movement, and physical therapy
Hypotonia was formally documented throughout childhood. Her family also describes recurrent muscle and leg pain, rapid physical fatigue, and a continuing role for physical therapy. In July 2026, her mother again emphasized extreme fatigue, rapid exhaustion, and frequent severe muscle pain. The genetics histories mention myalgias and rigidity or myotonia-like episodes, but no defined neuromuscular disorder or confirmed myotonia has been established.
Her pain communication is variable rather than absent. Serious ear disease could produce little visible distress, while the 2026 shoulder episode caused crying, inability to sleep, and obvious prolonged suffering. She may have difficulty recognizing, locating, communicating, or grading pain, so her outward behavior may not match the severity of a medical problem. She can also scratch herself or pull her hair more forcefully than she realizes and needs supervision to prevent injury.
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Cervical spine and left shoulder in 2026
In late March or early April 2026, she developed severe pain involving the left neck, trapezius, shoulder, and arm. Her mother later placed onset about six weeks before early May; urgent evaluation in April documented that the problem remained unresolved. The urgent-care note recorded left trapezius myogelosis, cervical or cervicothoracic biomechanical dysfunction, and pain with breathing. A short ECG showed no acute change. Ibuprofen 600 mg was listed as ineffective, and metamizole 500 mg four times daily plus 0.5 mL Xylonest 1% injected into a left trapezius trigger point were documented. Her family recalled a substantially higher ibuprofen dose, so the exact historical dose is uncertain. The pain severely disrupted sleep.
A cervical-spine MRI in April was obtained because left C4 radiculopathy was suspected. It showed straightening of the cervical spine, early loss of disc hydration at C4-5 and C5-6, and slight posterior disc protrusions with mild narrowing of the front of the subarachnoid space. Importantly, there was no focal disc prolapse, spinal-cord compression, myelopathy, abnormal cord signal, foraminal narrowing, or nerve-root compression. The scan therefore documented early cervical degenerative change but did not confirm compressive C4 radiculopathy.
A later clinical-genetics letter summarized the cervical finding as beginning osteochondrosis at C4-5 and C5-6 with disc protrusions. The geneticist raised a possible relationship to the ASH1L variant and cellular-aging research, but also stated that generalized premature aging has not been demonstrated in people with ASH1L variants. This possible connection remains unproven.
A left-shoulder MRI in May showed abnormalities that could contribute to the pain: stage 3 impingement, fibrosis of the supraspinatus tendon without rupture, and mild subacromial bursitis. The labrum and remaining tendons were intact, the humeral head position was normal, there was no acromioclavicular-joint hypertrophy, and there was no increased joint effusion.
A corticosteroid shoulder injection helped for approximately two weeks, but the pain returned. Although the family was initially told that surgery would be needed later in 2026, as of August the hospital was still assessing whether an operation could help. Additional physiotherapy and medical follow-up were planned. No operation had taken place.
In June, she reported pain behind the knees extending into the calves. A vascular referral records this pain together with dizziness or circulatory symptoms on standing and requests further evaluation. It does not establish a venous or arterial diagnosis.
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Skin, bruising, sweating, and contact sensitivity
Her mother describes sensitive, transparent or translucent skin, visible blue veins, easy or prolonged bruising, and reactions to plastic and sun exposure. No dermatologic diagnosis has been made.
Her family has also observed darker skin spots that sometimes seem to appear when she is cold. A new rash developed on both wrists in July 2026. Its appearance, trigger, and cause have not been established.
Heavy sweating - especially at night - is a prominent recurring feature. Her family reports that it contributes to skin irritation and recurrent bacterial or fungal skin infections. The childhood systemic illness also included marked night sweating, although those acute constitutional symptoms resolved during the 2011 admission.
A plaster or adhesive allergy is documented.
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Spinning dizziness after meals and posture changes
A June 2026 vascular referral records dizziness or circulatory symptoms on standing alongside pain behind the knees and calves. Her family later described severe spinning beginning as soon as she ate and also after rising from a squat. Reported assessments for diabetes, blood pressure, and venous and arterial causes had not explained the episodes.
The cause remains unknown. No vascular, cardiac, autonomic, glucose-related, or vestibular diagnosis has been established, and no current ENT or vestibular result has been reported.
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Gastrointestinal, nutrition, and hydration history
The clearest gastrointestinal event was the severe vomiting and gastrointestinal illness during the acute episode at age three. The family later mentioned gastrointestinal infections in the preschool years and current stomach pain, as well as menstrual pain. The current stomach pain remains unexplained.
Her family reports a sweet-food preference and large water intake. Glucose was 72 mg/dL in September 2025 and 74 mg/dL in May 2026, with HbA1c 5.2% on both occasions. These results did not indicate diabetes on those dates.
During the 2011 systemic illness, she had major weight loss and nocturnal urination, but abdominal ultrasound, celiac testing, thyroid testing, and the broader inpatient evaluation were unrevealing. Those acute constitutional symptoms improved before discharge.
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Growth, menstruation, hormones, and metabolic findings
During the January 2011 illness, she was tall and very slender at 137 cm and 20 kg. In March 2026, her family reported a height of approximately 154 cm and weight of approximately 45 kg. Her mother describes her as very slim and appearing considerably younger than her chronological age. No accelerated-aging disorder has been diagnosed.
Her mother has not noticed a distinctive facial difference.
Her family previously described menstrual cycles as regular at approximately 28 days, with menstrual pain. A 2026 clinical-genetics letter recorded menarche at 13, regular but light 32- to 34-day cycles, increased body hair, and limited breast development (micromastia).
SLINDA helped substantially for approximately two years. Her family then reported skin problems and the return of the earlier menstrual symptoms.
The clinical geneticist recommended assessment of estrogen, LH, FSH, and testosterone, including evaluation for possible primary ovarian insufficiency. The letter stated that low estrogen could increase ventricular-ectopy risk and might explain a reduced pubertal growth spurt; it also discussed hormone replacement as a possible option if deficiency were confirmed, both for physical and psychological well-being and for bone protection. Hormone-test results have not yet been reported. There is no established diagnosis of estrogen deficiency, ovarian insufficiency, perimenopause, osteoporosis, or a hormonal cause of her rhythm disorder.
Vitamin D was flagged low in January 2011 and again in May 2026. Thyroid testing in 2011 and 2026 remained within the displayed laboratory ranges and did not establish a thyroid disorder.
2018 postprandial lipoprotein analysis
A specialized postprandial lipid profile dated October 2018 was interpreted by the laboratory as disturbed triglyceride metabolism with low HDL and triglyceride-rich HDL, considered consistent with reduced lipoprotein-lipase activity. Dietary measures were advised. The report prints mg/dL for the listed lipid and apolipoprotein measures; the HDL-C/HDL-triglyceride ratio is unitless.
Growth, menstruation, hormones, and metabolic findings: 2018 postprandial lipoprotein analysis
Measure
Value
Total cholesterol
136
Triglycerides
194
HDL cholesterol
40
LDL cholesterol
59
Available LDL
49
LDL triglycerides
28
VLDL cholesterol
44
VLDL triglycerides
116
VLDL ApoB
27
LDL ApoB
53
ApoB
80
ApoA-I
101
HDL-C/HDL-TG ratio
0.8, unitless
Lipoprotein(a)
3
Small-dense LDL ApoB
10
Small-dense LDL cholesterol
10
2 OCTOBER 2018 · POSTPRANDIAL ANALYSIS
Selected reported lipoprotein measures.
All plotted values use the report’s printed mg/dL unit. This was a specialized postprandial analysis, not a current fasting lipid panel; the full table and laboratory interpretation remain in the profile.