List of symptoms

symptomsAlthough children who are diagnosed Bohring-Opitz Syndrome (BOS) have a lot in common, each child is different and unique. The list of ailments and physical characteristics associated with the syndrome is long, but not every child has all or the same symptoms.  Every child develops at his or her own pace, and the variation in level of development from one child to the next can be great.

Anna Doggett, a grandmother of a little boy with BOS from the United Kingdom, surveyed 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).

Clinical Symptoms

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

Craniofacial Symptoms

  • Microcephaly (abnormally small head)
  • Trigonocephaly (premature fusion of the metopic suture)
  • Micro/retrognathia (abnormal posterior positioning of the maxilla or mandible)
  • Flammeaus nevus (birth mark)
  • Prominent eyes
  • Abnormal (high) palate
  • Hypertelorism (abnormally large  distance between the eyes)
  • Proptosis  (a condition resulting in forward displacement and entrapment of the eye from behind by the eyelids)
  • Up slanting palpebral fissures  (the elliptic space between the medial and lateral canthi of the two open eye lids)
  • Epicanthal folds (the skin of the upper eyelid, from the nose to the inner side of the eyebrow, that covers the inner corner (canthus) of the eye)
  • Broad alveolar ridge (one of the  two jaw ridges either on the roof of the mouth between the upper teeth and  the hard palate or on the bottom of the mouth behind the lower teeth)
  • Cleft/notch lip
  • Cleft palate
  • Buccal frenulae (skin connecting  the cheek to the gums)
  • Depressed nasal bridge
  • Anterverted nares (nasal openings are tipped upwards)
  • Low-set posteriorly rotated ears
  • Retrognathia (the jaw is set back)
  • Short philtrum (space between upper lip and tip of nose)
  • Choanal Atresia (a congenital disorder where the back of the nasal passage (choana) is blocked)
  • Laryngomalacia (common cause of stridor in infancy, in which the soft, immature cartilage of the upper larynx collapses inward during inhalation, causing airway obstruction)

Ophthalmic – Eye symptoms

  • Strabismus (squint, cross eyed)
  • Anterior chamber abnormalities  (the fluid-filled space inside the eye between the iris and the cornea’s innermost surface)
  • Myopia (short-sighted)
  • Retinal/optic nerve abnormalities
  • Absence of tears
  • Glaucoma (a group of eye  conditions in which the optic nerve is damaged due to changes in eye pressure)
  • High intraocular pressures initially (causes damage to the optic nerve, which can lead to glaucoma)
  • Thick Cornea (corneal thickness is an important factor in accurately diagnosing eye pressure)
  • Excavatie (excavation of optic disc)

Hair/Skin

  • Low hairline
  • Hypertrichosis (abnormal hair density and length)
  • Hirsutisme dorsal (hairy back)
  • Synophrys (abundant hair between  the eyebrows)

Congenital dislocations/Skeletal

  • BOS Posture[1]
  • Scoliosis (curvature of the spine)
  • Fixed constrictors of the upper  limbs
  • Rhizomele humerus (shortening of the humerus and femur)Absence of distal interphalangeale crease from fingers
  • Deviation from fingers (a hand deformity in which the swelling of the metacarpophalangeal joints (the big knuckles at the base of the fingers)
  • Dropping/clenched hands (BOS  posture)
  • Bilateral hip dysplasia/luxation (dislocation of the hips)
  • Thoracic kyphosis (also called round back or Kelso’s hunchback), is a condition of over-curvature of the thoracic vertebrae (upper back)
  • Platyspondilie thoracal (narrowing of the intervertebral disc spaces in the upper lumbar and lower thoracic spine and clefting of the posterior end plates at L2-4)
  • Dandy-Walker-Syndrome
  • Short stature
  • Hypertonia ( a condition of  excessive tone of the skeletal muscles; increased resistance of muscle to passive stretching)
  • Hypotonia (low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength)

Brain abnormalities/Neurological

  • Brain abnormalities
  • Cavum septum pellucidum (this is a  problem with the ‘soft spot’)
  • Hypoplasia partial agenesis posterior  corpus callosum (The Corpus Callosum is the central region of the human brain consists of nerve tissue which convey  “messages” between the two hemispheres. This part is only partially formed or not formed at all.
  • Spina bifida occulta (The mildest form of spina bifida, spina bifida occulta describes a group of neural  tube birth defects that can affect the spinal column.)
  • Dystonia

Cardiology

  • Cardiac abnormalities
  • ASD (Atrial Septal Defect) and Patent Foramen Ovale (PFO). Congenital heart defect in which there is an abnormal opening in the dividing wall between the upper filling chambers of the heart (the atria).
  • Arrhythmias (irregular heartbeat)
  • Bradycardia (slow heart rate)
  • long QT syndrome (irregular heartbeat)

Gastroenterology

  • Emesis (vomiting)
  • Intestinal Malrotation (intestines are not in the normal position)
  • Fundoplication (a surgical procedure to treat gastro esophageal reflux disease)
  • Gastrostomy
  • NG Tube
  • Constipation
  • Eating solid food
  • Gallstones
  • Hyperechogenic pancreas
  • Chronic pancreatitis (CFTR mutations in one patient confirmed)

Urology/Nephrology

  • Recurrent urinary tract infections
  • Thickened bladder wall
  • Infravesical obstruction (bladder  outlet obstruction)
  • Residue (urinary retention)
  • Horseshoe kidney (ren arcuatus, kidneys fuse together to form a horseshoe-shape)
  • Renal abnormalities
  • Wilms Tumor’s

Development/Behavior

  • Some able to communicate verbally
  • Some able to walk
  • Stereotypic movement disorder (SMD)/stereotypic movements/behaviour like winds hands and straightens legs when showing emotion, forefinger in mouth, head shaking

Other

  • Silent aspiration (Silent aspiration occurs in people that have swallowing problems, which is known as dysphagia. Aspiration is when food, liquids, or stomach contents are swallowed poorly, and go into the lungs.
  • Sleep disturbances (insomnia, hypersomnia, sleep apnea)
  • High pain tolerance
  • Hearing Impairment
  • Anemia / Thalassemia (a form of anemia)
  • Polythelia (the presence of  supernumerary nipples)
  • Inguinal hernia
  • Precocious puberty
  • Quick growing finger and toe nails
  • Hyperthermia
  • Hypoxia

[1] 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)

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