List of symptoms

Although children with Bohring-Opitz Syndrome often look alike, and their clinical phenotype at birth is extremely similar, each child is unique and may be affected differently. Not every child will have all the classic physical characteristics, and the variation in levels of development from one child to the next can be great. This Interactive Visual Aid and list, based on published medical literature and case studies between 2006 – 2024[1], are for information only, and do not claim to be complete, but can be used as a guide. Furthermore this interactive visual aid and list are not intended to be a substitute for professional medical advice, diagnosing criteria, or treatment. Always seek the advice of your physician and/or other qualified healthcare providers for any questions you may have regarding a medical condition.

Download here the printable Pdf “Bohring-Opitz Syndrome/ASXL1 – List of Symptoms”

Clinical Symptoms

  • Feeding difficulties
  • Failure to thrive
  • Intrauterine growth restriction (IUGR)
  • Severe/profound learning  difficulties
  • Recurrent infections
  • Seizures
  • Apneas (suspension of external breathing)

Craniofacial – Head

  • Microcephaly
  • Broad, narrow, bulging, prominent forehead
  • Trigonocephaly / Craniosynostosis (premature fusion of the metopic suture)
  • Prominent metopic ridge
  • Hypoplastic orbital ridges
  • Micro/retrognathia
  • Hypotonic facies with full (puffy) cheeks
  • Facial asymmetry
  • Long face at a later age
  • Small anterior fontanel

Eye & Vision

  • High Myopia (near-sighted)
  • Strabismus, Exotropia (alignment of eye)
  • Nystagmoid (purposeless) movements
  • Anterior chamber, Retinal, Optic nerve abnormalities, Large cup to disc ratio
  • Absence of tears
  • Poor visual interaction
  • (Cortical) Visual impairment (vision loss)
  • Prominent eyes
  • Exophthalmos / Proptosis (bulging eyes)
  • Hypertelorism (widely spaced eyes)
  • Upward slanting palpebral fissures  
  • Epicanthal folds

Corrective lenses
Regular follow up for vision optimization

ENT & Dental issues

Clinical signs and symptoms of ear, nose, mouth, and throat, as well as dental issues.

Nose
  • Depressed nasal bridge
  • Wide nasal bridge
  • Anteverted nares (upturned nasal tip)
  • Short/long philtrum (vertical grove between nose and mouth)
  • Choanal atresia (blocked nasal airway)
Throat/Mouth
  • Broad alveolar ridge, alveolar ridge overgrowth
  • Abnormal (high and narrow) palate
  • Unilateral and bilateral cleft/notch lip and/or palate, bifid uvula
  • Buccal frenula
  • Prominent palatine (tonsils) ridges
  • Tongue-based airway obstruction (caused by micrognathia)
  • Overproduction of salvia and mucous
  • Narrow mouth
  • Laryngomalacia and subglottic stenosis (narrowing of airway)

Mandibular distraction (surgery lengthening jaw)
Tongue-lip adhesion
Referral to craniofacial team
Primary closure of cleft lip

Ear
  • Low-set posteriorly rotated ears
  • Overfolding helices (ear)
  • Small ear canals (ear canal stenosis)
  • Hearing loss
  • Ear infections
  • Hearing impairment
Dental Issues
  • Delayed dental eruption
  • Gingival hyperplasia or hypertrophy (abnormal overgrowth of gingival tissue)
  • Widely spaced teeth
  • Teeth grinding

Skin & Hair

  • Nevus flammeus nevus (birth mark) on glabellar and eyelids
  • Hypopigmented spot(s) on chest
  • Cutis Laxa (loose skin)
  • Deep palmer creases (a deep line in the palm)
  • Sacral dimple (indentation in the skin on the lower back)
  • Hypertrichosis (excessive hair or abnormal hair density and length)
  • Low posterior hairline
  • Synophrys (unibrow, abundance of  hair between the eyebrows)
  • Rapid hair and nail growth
  • Hirsutism dorsal (hairy back)

Growth & Feeding

  • Intrauterine growth restriction (IUGR) 
  • Growth retardation (postnatal growth restriction)
  • Underweight
  • Short stature
  • (Infant) Feeding difficulties
  • (Cyclic) Emesis (vomiting)
  • Oral motor impairment
  • Failure to thrive
  • Obesity at later age

Feeding therapy
Identifying and avoiding triggers for cycling vomiting

Gastrointestinal

  • Emesis (vomiting)
  • Gastro-esophageal reflux disease
  • Paraoesophageal hernia
  • Intestinal malrotation
  • Constipation
  • Inguinal hernia
  • Abdominal distension

Gastrostomy
Nasogastric Tube (NG Tube)
Nissen Fundoplication
Volvulus ostomy
Intestinal resection
Close monitoring of feeding intolerance

Biliary & Metabolic System

  • Gallstones
  • Hyperechogenic (fatty) pancreas
  • Annular pancreas
  • Chronic pancreatitis
  • Hepatoblastoma (liver tumor)
  • Splenic cyst
  • Metabolic abnormalities
  • Hypothyroidism (underactive thyroid)

Abdominal ultrasound every 3 months from birth to eight years 
and measurement of alpha-fetoprotein (AFP) via blood draw every three months until age 5
to detect the development of Hepatoblastoma

Cardiovascular System

  • Cardiac abnormalities
  • Atrial and/or Ventricular Septal Defect (congenital heart defect, hole in the wall of two heart chambers)
  • Arrhythmias (irregular heartbeat) 
  • Bradycardia (slow heart rate)
  • Cardiac hypertrophy (thickened heart muscle)
  • Heart murmur
  • Dilated cardiomyopathy (enlarged heart chamber)
  • Congestive heart failure

Respiratory System

  • Respiratory distress (Neonatal)
  • Obstructive sleep apnea
  • Silent aspiration
  • Dyspnea (shortness of breath)
  • Pulmonary hypertension
  • Recurrent infections

Noninvasive pressure support
Tracheostomy
Polysomnography (sleep study to identify early obstructive apnea)
Aggressive management of chronic emesis

Urology & Nephrology

  • Recurrent urinary tract infections (UTI)
  • Renal pelvicalyceal dilatation (widening of the renal pelvis)
  • Vesicoureteral reflux
  • Urinary retention
  • Incontinence (not toilet trained)
  • Renal (kidney) abnormalities
  • Horseshoe kidney
  • Renal stones
  • Renal cysts
  • Wilms Tumors

Renal ultrasound (every 3 months from birth to eight years to detect the development of Wilms tumor)
Urinalysis for possible UTI

Genitourinary & Puberty

  • Early puberty / early onset
  • Dysfunctional uterine bleeding
  • Genital abnormalities
  • Penile adhesions
  • Hypospadias (abnormality of anterior urethral and penile development)
  • Undescended testicle
  • Widely spaced intermammillary nipples (the presence of an additional nipple)

Musculoskeletal System – Muscles

  • Hypotonia (low muscle tone)
  • Hypertonia (high muscle tone)
  • Spastic paraparesis (weakness and stiffness in the leg muscles)
  • Dystonia/dystonic posturing
  • Flexion contracture
  • Motor delay/impairment

Walkers and braces

Muscuskeletal System – Body

  • BOS Posture (fixed constrictors of the upper limbs)[2]
  • Scoliosis (curvature of the spine) 
  • Lordosis (inward curvature of the lower back)
  • Thoracic kyphosis (Kelso’s hunchback)
  • Enlargement of vertebral foramina (dorsal and lumbar regions)
  • Bony thorax abnormalities (narrow thorax, sunken chest)
  • Bilateral hip dysplasia/luxation
  • Segmental overgrowth

Spinal fusion surgery

Musculoskeletal System – Hand & Feet

Hand
  • Ulnar deviation, flexion of wrist and fingers
  • Overlapping toes and/or fingers
  • Absent/single palmar crease
  • Brachydactyly (short digits)
  • Preaxial polydactyly (extra digit(s) are localized on the side of the thumb or great toe)
  • Fetal pads
  • Camptodactyly (fingers fixed in a bent position at the middle joint and cannot fully straighten)
Feet
  • Genu valgum (knock knees)
  • Clubbed feet
  • Small feet
  • High arched feet
  • Metatarsus adducts (front foot turned inward)
  • Talipes valgus (deformity of the feet)
  • Increased sandal gaps

Cognitive Development

  • Severe/profound learning difficulties
  • Global development delay
  • Cognitive disability
  • Severe/profound intellectual disabilities
  • Autism

Early intervention programs
Individual education plans
Occupational therapy
Physical therapy
Medical equipment

Communication

  • Delayed/Absence speech development
  • Nonverbal
  • Lack of expressive language
  • Language impairment
  • Decreased expressive communication

Speech therapy
Augmentative and Alternative Communication (ACC) Strategies

Behavioral

  • Stereotypic movement disorder, repetitive behavior
  • Breath holding spells
  • Lack of stranger anxiety
  • Hypersensitivity
  • Hyperactive
  • Frequent tantrums
  • Self-injurious behavior (eye poking)
  • Pleasant and happy demeanor
  • Curious, alert, and interactive

Sleep

  • (Obstructive) Apneas (suspension of external breathing)
  • Sleep disturbances
  • Insomnia and/or Hypersomnia
  • Excessive sleepiness (narcolepsy)
  • Fatigue
  • Irregular sleep/wake cycle
  • High sleep latency

Severe obstructive sleep apnea may be treatable by tonsillectomy, adenoidectomy, or mandibular distraction
Melatonin
Treatment of anemia

Neurological

  • Brain abnormalities
  • Brain activity abnormalities on MRI imaging
  • Hypoplasia /Agenesis corpus callosum
  • Cerebral Cortex anomalies
  • Delayed peripheral myelination
  • Enlarged ventricles (brain)
  • Bulbar dysfunction
  • Dandy-Walker-Syndrome
  • Epilepsy / Seizures
  • Cyst on conus (spinal)
  • Sacral hair patch / arachnoid cyst

Bewa

Bewaren

Bewaren

Bewa

[1] Bohring et al. 2006, Pierron et al. 2009, Hasting et al. 2011, Magini et al. 2012, Russell et al. 2013, Russell et al. 2015, Dangiolo et al. 2015, Arunachal et al. 2016, Kibe et al. 2018, Urreitzti et al. 2018, Bedoukian et al. 2018, Russell et al. 2018, Quintero et al. 2019, Efthymiou et al. 2019, Rohanizadegan et al. 2020, Leon et al. 2019, Zhao J. et al. 2021, Cuddapah et al. 2021, Zhao W. et al. 2021, Joshi et al. 2023, Russell et al. 2023, Ayoub et al. 2023, Patel et al. 2024

[2] BOS posture of the upper limbs (defined as having three out of four features: exorotation and/or adduction of the shoulders; flexion at the elbows; flexion at the wrists; and ulnar deviation of the wrists and/or fingers at the metacarpophalangeal (MCP) joints) (Hasting et al. 2011)

Treatment options based on Russell B, Tan WH, Graham JM Jr. Bohring-Opitz Syndrome. 2018 Feb 15. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK481833/

Anna Doggett, a grandmother of a little boy with BOS from the United Kingdom, surveyed 2015 parents who participate in the online Bohring-Opitz Facebook Group about the physical characteristics and symptoms their child has or has experienced.  The parents were asked to read through a form list of symptoms and indicate those that applied to their child.  The parents were also asked to add symptoms to the list, if the symptom was not indicated in the survey.  The survey is based on a list of physical characteristics and symptoms found in a medical publication (Hastings, Rob et al.,(2011) Bohring-Opitz (Oberklaid-Danks) syndrome: clinical study, review of the literature, and discussion of possible pathogenesis. European Journal of Human Genetics).  To date a total of eleven children have been identified in the survey.

» BOS symptoms (pdf)

» BOS symptoms percentage (pdf)

Almost all the BOS children who participated in the study have distinguishable physical features.  They nearly all have a typical appearance, and if you were to compare the children at a very young age, they look as though they all could be siblings. Typically, all have a (heart-shaped) Flammeaus nevus (birth mark) and prominent eyes (82%) with Myopia and absence of tears. All children who participated in the survey had an abnormal palate and low-set posteriorly rotated ears.  Other typical marks were Microcephaly (abnormal small head) and Trigonocephaly.  Some of the children also have cleft palate/lip (36%|18%). The hair of BOS children is also very particular, as most have an abundance of hair (abnormal hair density and length).

Many parents also described their children with having the typical BOS-posture (91%), which includes dropping/clenched hands (82%). It was indicated that the children often suffer from Hypotonia (low muscle tone) (91%).  The parents’ research also indicated that half of the children have brain abnormalities, such as Hypoplasia of the brain and/or partial agenesis of the corpus callosum (55%|45%).

Most children have significant feeding problems (91%).  Many of the parents indicated that uncontrollable vomiting was frequent, especially within the first year of life.  Most of the children with severe feeding issues are often feed through the use of nasal gastric tubes or gastronomy tubes.  Despite these statistics, about half of the children learned to eat by mouth.  Most of the children in the study were found to suffer from stunted growth (55%) and delayed development (100%).   Half of the children who were represented in the study also had frequent, recurring respiratory infections.  Lastly, the research indicated that a majority of the children also suffer from constipation (64%) and recurrent urinary tract infections.

Prior to 2011 there was no DNA test to confirm a diagnosis of Bohring-Opitz Syndrome.  Geneticists relied on making a clinical diagnosis by recognizing the distinguishable physical characteristics in the appearance of the child, and with the aid of clinical research. Now it is possible to confirm the BOS diagnosis with a genetic DNA test (whole exome sequencing, or whole genome decoding).