Normalized MANE/map notationNM_018489.3:c.4902_4903del · NP_060959.2:p.Ser1635Cysfs*18 — The original report uses NM_018489.2. NM_018489.2 and MANE Select NM_018489.3 use the same coding coordinate here, so c.4902_4903del and p.Ser1635Cysfs*18 map 1:1.
A boy in the 11–15 age group with a gentle nature, a strong memory, and a lifelong history of developmental, communication, motor, oral, feeding, and sensory differences
He is a gentle, curious, and observant adolescent who is drawn to patterns and how things work. His interests have included flags and national capitals, languages, reading, mathematics, science, planets, dinosaurs, electronics, and videos about repairing or refurbishing devices. He has taught himself a substantial amount of French and has long shown a remarkable memory for information that captures his attention.
Dogs are especially important to him. They have brought him joy and have sometimes made it easier for him to begin conversations or connect with unfamiliar people. He has friendships at school, although social communication and building relationships with other adolescents can still be difficult.
He wants to participate and do things for himself. He can make his preferences clear, ask for help or clarification, and take pride in completing tasks independently. His abilities and support needs do not develop at the same rate: strong reading, memory, and factual interests coexist with challenges in conversation, comprehension, motor planning, handwriting, eating, attention, and everyday independence.
02
Genetic diagnosis
The original 1 November 2019 trio exome report identified a heterozygous Pathogenic ASH1L variant, NM_018489.2:c.4902_4903del (p.Ser1635Cysfs*18). The report states that the variant was de novo and shows it absent in both parents.
The result provided a molecular diagnosis in 2019, after more than two years of pursuing a genetic evaluation. His clinical history includes autism, developmental and speech delay, delayed fine- and gross-motor development, oromotor apraxia, feeding difficulty, and gastrointestinal symptoms.
03
Birth and infancy
He was delivered by cesarean section after remaining in a breech position from approximately 28 weeks of pregnancy. His family recalls that the umbilical cord was around his neck. His birth weight was approximately 2.97 kilograms.
He latched and breastfed during his first five days. On day six, he developed severe nasal blockage and did not latch again. Infancy also included colic, recurrent nasal or flu-like symptoms treated with antibiotics and nebulizer therapy, reflux, vomiting, and feeding difficulty.
His family remembers his development as appearing broadly typical during approximately the first six months. He rolled early and sang to himself at bedtime. Later in infancy, sudden severe constipation led to hospitalization and treatment with an enema. After he returned home, his family noticed that he no longer used his previous crawling pattern. Instead, he lay on his back and pushed with his legs to move toward objects.
By age one, he was not yet crawling, walking, or talking. Constipation became severe enough to cause painful rectal lesions. His treatment history included rectal medication, repeated enemas, and Milk of Magnesia through toddlerhood.
During this period, his family was told that his vitamin D level was markedly low and that there was concern about rickets. He received vitamin D injections and intensive occupational therapy. Crawling and independent walking emerged during the months that followed. This sequence is part of his history, although it does not by itself establish what caused the motor gains.
Chapter 02Development, communication, regulation, and movement
04
Developmental course and autism
During toddlerhood, after an episode of hand-foot-and-mouth disease, his family observed a marked change in development. He made less eye contact, stopped responding consistently to his name, stopped babbling, and had periods described as “zoning out.” Although he could walk, his gait remained wobbly, and climbing, jumping, and keeping up with other children were difficult.
His family also observed hand flapping, spinning objects, repeatedly rewinding short sections of videos, and opening and closing cabinet doors. At approximately age three, when he was still non-speaking, he was diagnosed with autism and began applied behavior analysis and speech therapy.
Phonic sounds emerged at approximately three years four months, followed by a small number of words around age four. By age seven, he was speaking English and French, although conversational language and social interaction still required substantial support and cueing.
He has autism spectrum disorder. Attention, follow-through, and executive function are also areas of need and are addressed through therapy and school supports.
05
Communication, learning, and school
His communication profile includes significant growth alongside persistent needs in motor speech, articulation, pacing, intelligibility, receptive and expressive language, conversational exchange, and social communication. A published description recorded oromotor apraxia. When he speaks quickly, words may blend together, and he may need support with pausing, rhythm, intonation, phrasing, and making his message clear. He can ask questions and request clarification, but maintaining a conversation and carrying an instruction through to completion may require prompting.
He is a middle-school student with an individualized education program. He participates in both supported and integrated classes. Reading individual words is a relative strength, while understanding and explaining what he has read can be harder. Handwriting remains effortful, particularly spacing, line placement, copying, and maintaining consistent letter formation.
At age eight, a published assessment reported a Shipley score of 101. The authors interpreted that result as average cognitive functioning without intellectual disability at that assessment. Adaptive-function testing indicated low adaptive functioning, showing that his practical daily support needs were greater than the cognitive score alone would suggest.
His love of reading, science, geography, mathematics, technology, and languages remains an important part of how he learns and connects with the world.
06
Attention, sensory regulation, and social participation
Movement and repetitive activity have long helped him regulate. At times, frequent self-stimulatory movement can make it harder to sustain attention, shift between activities, or complete a routine. A recent occupational-therapy assessment described a mixed sensory pattern that included seeking, avoidance, heightened sensitivity, and reduced registration, with auditory, oral, and attention-related differences especially prominent.
He may need moderate prompting to remain with a task, understand a multistep direction, or complete an activity. He can also be determined and independent: during occupational therapy, he selected a climbing activity, wanted to complete the assessment himself, and participated actively with support.
His family has described anxiety around peers and difficulty developing or sustaining friendships. He generally gets along with others and has friends at school, but same-age relationships outside school remain limited, and interaction with adults can sometimes be easier. His interest in dogs can provide a natural bridge into social connection.
07
Motor development and neurological findings
A 22 April 2017 FDG-PET report described severe bilateral cerebellar hypometabolism with otherwise preserved cerebral uptake. The chart below compares the report’s regional mean SUV values within that scan; it does not show change over time or a cohort pattern.
His motor history includes delayed crawling and walking, a wobbly early gait, difficulty climbing and jumping, and delayed fine- and gross-motor development. With time and therapy, he made meaningful gains. By later childhood, he could ice skate and ride a bicycle with training wheels.
At age eight, a published assessment documented dysmetria and an abnormal ataxic gait, with difficulty coordinating movement and maintaining balance. A later publication reported a history of hypotonia, although hypotonia was not identified during the age-eight assessment.
More recent occupational-therapy findings describe continuing needs in balance, bilateral coordination, motor planning, visual-motor integration, core and shoulder stability, fine-motor control, handwriting, and endurance. Compensatory head or trunk movement may appear when a task places greater demands on coordination.
A formal brain FDG-PET scan at age three showed severely reduced uptake in both cerebellar hemispheres, while uptake in the remainder of the brain was preserved. The radiology impression was severe bilateral cerebellar hypometabolism. The scan documents an imaging finding; it does not by itself explain its cause or determine how it relates to his development.
His family observed “zoning out” in toddlerhood. No seizures were reported in the age-eight assessment, and the available history does not establish a seizure disorder.
22 APRIL 2017 · ONE FDG-PET STUDY
Reported regional mean SUV values.
The bars compare the report's left and right regional mean standardized uptake values within this single scan. They are not normative z-scores, a longitudinal trend, or a disease-severity scale. The report's qualitative interpretation is summarized above. The chart writes two shortened region labels in full: cingulate/paracingulate and calcarine fissure.
Frontal
Left4.17 mean SUV
Right4.02 mean SUV
Temporal
Left3.86 mean SUV
Right3.86 mean SUV
Parietal
Left4.21 mean SUV
Right4.05 mean SUV
Cingulate / paracingulate
Left3.96 mean SUV
Right3.69 mean SUV
Central
Left4.14 mean SUV
Right3.95 mean SUV
Occipital
Left4.01 mean SUV
Right4.13 mean SUV
Calcarine fissure region
Left4.28 mean SUV
Right4.34 mean SUV
Basal ganglia
Left3.86 mean SUV
Right3.86 mean SUV
Mesial temporal
Left2.74 mean SUV
Right2.71 mean SUV
Cerebellum
Left2.53 mean SUV
Right2.35 mean SUV
Chapter 03Hearing, oral development, eating, and sensory safety
08
Hearing and listening in complex environments
Formal audiology found normal peripheral hearing, normal middle-ear function, and 100% word recognition in quiet.
The more significant difficulty appears when listening becomes complex. Testing showed a reproducible weakness when he had to direct attention to competing speech presented to both ears. Directed-ear recall fell in the disordered range, while free recall and competing-sentence performance were borderline. Other tested areas were within the evaluation’s expected range.
He did not meet that evaluation’s full criteria for auditory processing disorder. The most accurate description is a documented competing-speech or dichotic-listening weakness with normal peripheral hearing. In daily life, this may make spoken information harder to follow in classrooms, groups, or other noisy settings even though he hears quiet speech clearly.
09
Oral development and dentition
His oral and dental development is one of the most important parts of his history. Primary tooth eruption was markedly delayed, with most teeth appearing only around age three. The family remembers the eruption as unusually quiet, with little obvious teething pain.
Permanent teeth also emerged late. Primary teeth remained into early adolescence while permanent teeth attempted to erupt. He required dental surgery to remove retained primary teeth and make room for permanent eruption.
Available dental material describes molar-incisor hypomineralization and enamel erosion. His family has observed white areas on the enamel and molars that looked unusually soft or “spongy,” leading to frequent monitoring for decay.
Labial and lingual tethering went unrecognized for years. He later underwent tether-release procedures and continued with feeding and myofunctional therapy. Orofacial assessments have described an open-mouth resting posture, reduced lip closure, a low tongue resting posture, tongue-jaw dependence, limited tongue elevation and lateralization, reduced posterior-tongue mobility, and excessive facial-muscle recruitment during oral tasks.
10
Chewing, swallowing, and food safety
His family reports that he has never developed an effective, reliable chewing pattern. Since the introduction of solid food, he has struggled to bite, move food from side to side, grind it, coordinate the tongue and jaw, and organize it into a manageable bolus. He continues to depend heavily on soft or baby-food textures.
At times, he has used head movement, tilting, or gravity to help move food through his mouth. Evaluations and family observations have described open-mouth chewing, unilateral chewing, uneven oral awareness, and difficulty breaking food down before swallowing.
His feeding history includes severe gagging when a small piece is present, coughing, choking concern, apparent difficulty breathing during some episodes, loud burping, and vomiting. Vomiting became much less frequent after approximately age five, but safe food preparation, texture control, pacing, and supervision remain important.
The main concern is the oral preparation and movement of food: inadequately chewed pieces can lead to gagging, coughing, choking, or vomiting.
11
Taste, smell, temperature, hunger, and oral sensitivity
His oral sensory profile is strikingly mixed. His family observes markedly reduced warning from strong flavor, spice, and odor. He may eat green chili without showing the expected oral reaction. He often needs a very close, deep inhalation to notice an odor and has had difficulty distinguishing coffee from tea by smell. Reduced warning from flavor and odor also raises practical concern about recognizing spoiled food.
Physical food temperature is different. He recognizes warmth but cannot tolerate food that is hot or even lukewarm, preferring it cold or at room temperature.
His family has also observed limited awareness or communication of hunger.
At the same time, the tissues inside his mouth appear highly vulnerable to irritation. His family reports extensive ulcers after fluoride-containing or strongly foaming toothpaste. Rougher brushing can cause bleeding followed by ulceration. Oral-care products and brushing technique therefore require careful selection and monitoring.
Chapter 04Gastrointestinal, sleep, airway, endocrine, and broader health
12
Gastrointestinal history
Severe constipation began in infancy and required hospitalization, enemas, rectal medication, and prolonged use of Milk of Magnesia. His family reports that the constipation later improved during toddlerhood.
Reflux, vomiting, gagging, and excessive burping were also prominent in early childhood. A published assessment records feeding difficulty and excessive infant reflux and vomiting. Vomiting became substantially less frequent after age five, although oral-motor and chewing problems continued.
13
Sleep and airway
He has long slept with his mouth open. Later orofacial assessments described lips resting apart, reduced lip closure, daytime and nighttime mouth breathing, and intermittent snoring.
His current sleep is reported to last approximately nine to ten hours, and he generally wakes with energy. Mouth-open sleep and intermittent snoring remain important airway observations, although he has not been diagnosed with obstructive sleep apnea.
14
Endocrine, laboratory, and broader medical history
In toddlerhood, his family recalls fluctuating TSH results that were monitored for approximately four months without medication and later returned to the expected range. No chronic thyroid disorder has been established from the available history.
His family also remembers unspecified kidney- and liver-related laboratory elevations during toddlerhood. They were told that an ultrasound did not show structural damage. The exact analytes and report are unavailable, and this history does not establish chronic kidney or liver disease.
Formal testing in 2025 showed IgA, IgG, IgM, IgE, IGF-1, IGFBP-3, morning cortisol, and ACTH within the laboratory’s displayed reference intervals.
The same testing flagged low C4 and elevated C5OH, C5:1, C10:2, C14, and C16OH. Earlier urine organic-acid testing flagged urinary oxalate on two occasions, with additional flags involving tricarballylic acid, arabinose, and pantothenic acid. These findings were not accompanied by a metabolic diagnosis or specialist interpretation.
Chapter 05Therapies, daily life, independence, and the whole person
15
Current therapies, daily life, and independence
His current supports include occupational therapy, speech-language therapy, feeding therapy, and myofunctional work. Major goals include clearer and more effective communication, safe chewing and oral-motor coordination, handwriting, shoelaces, attention and executive function, motor planning, meal preparation, social participation, and greater independence in daily routines.
He is independent in many personal-care tasks, including toileting, bathing, grooming, and dressing. He can manage buttons and zippers, although some tasks take extra time. Shoelaces, handwriting, sequencing, and more complex daily activities remain areas of active work.
He benefits from clear language, extra processing time, reduced competing noise, visual or stepwise support, and prompting that helps him complete a task without taking over his effort. Food requires careful texture preparation and supervision. Oral hygiene requires products and techniques that do not trigger bleeding or ulcers.
16
The whole person
His development has been uneven, but it has never been static. He has moved from being non-speaking to communicating in more than one language; from delayed walking and an unstable gait to skating and cycling with support; and from needing help with basic routines to completing many personal-care tasks independently.
He continues to need meaningful support with communication, comprehension, attention, coordination, handwriting, social participation, chewing, food safety, and higher-level daily living. Alongside those needs are a strong memory, broad intellectual interests, affection for dogs, curiosity about technology and the world, and a clear desire to participate and do things for himself.
His ASH1L diagnosis is one part of his story. Understanding him requires seeing his abilities and interests together with the developmental, motor, oral, sensory, feeding, and adaptive differences that shape his everyday life.