BRESEK syndrome is an extremely rare, inherited condition that affects many body systems from birth. The name is an acronym that summarizes its key features: Brain anomalies, severe Retardation (intellectual disability) and growth delay, Ectodermal dysplasia (problems of skin, hair, nails, teeth), Skeletal deformities (especially of the spine and limbs), Ear/eye anomalies, and Kidney dysplasia or small kidneys. Many children show thin or under-formed parts of the brain (such as a thin corpus callosum), significant learning and developmental challenges, sparse hair or no hair, dry scaly skin, curved spine (scoliosis) or extra fingers/toes, hearing loss, eye underdevelopment, and kidney malformations. The condition is ultra-rare and has been described mainly in boys from the same family, which fits with an X-linked pattern of inheritance. rarediseases.info.nih.gov+2NCBI+2
BRESEK (and the broader BRESHECK spectrum) is a multiple congenital malformation disorder defined by Brain anomalies, severe intellectual Retardation (now termed intellectual disability), Ectodermal dysplasia, Skeletal deformities, Ear/eye anomalies, and Kidney dysplasia/hypoplasia. The condition was first described in two half-brothers; later work linked the spectrum to MBTPS2 gene defects on the X chromosome and to phenotypic overlap with IFAP (ichthyosis follicularis, atrichia, and photophobia). Only a handful of male patients have been reported, underscoring how little disease-specific trial evidence exists; care therefore follows organ-specific best practices. rarediseases.org+6PubMed+6onlinelibrary.wiley.com+6
Because many patients have ectodermal dysplasia features (hair/teeth/sweat gland abnormalities), supportive measures such as skin care, dental rehabilitation, and temperature regulation are central. Similarly, when Hirschsprung disease or hearing/vision/kidney problems are present, modern pediatric surgical, audiologic, ophthalmic, and nephrology pathways are used. The sections below organize these into non-drug therapies, medicines (with FDA label citations), dietary supplements (general evidence), advanced/“regenerative” options, surgeries, prevention, diet, and practical triggers to seek care. PMC+5Cleveland Clinic+5Medscape+5
Another names
Doctors sometimes use closely related names because the features overlap:
BRESHECK syndrome – this adds Hirschsprung disease (a bowel nerve problem), Eye hypoplasia, Cleft palate or Cryptorchidism (undescended testes) to the core BRESEK picture. In the literature, “BRESEK/BRESHECK” is commonly written together. Pediatric Neurology Briefs+2onlinelibrary.wiley.com+2
IFAP syndrome 1, with or without BRESHECK – IFAP stands for Ichthyosis Follicularis, Atrichia, Photophobia. Some patients with IFAP also have the broader BRESHECK constellation; these disorders share the same gene and lie on one clinical spectrum. NCBI+2disorders.eyes.arizona.edu+2
Types
Because this disorder is so rare, there is no formal, universally agreed list of “types.” Clinically, specialists think of a spectrum with two practical groupings:
BRESEK pattern – brain anomalies + severe developmental/intellectual disability + ectodermal dysplasia + skeletal changes + ear/eye anomalies + kidney dysplasia. rarediseases.info.nih.gov+1
BRESHECK pattern – the BRESEK pattern plus Hirschsprung disease, and/or eye hypoplasia, cleft palate, cryptorchidism; many authors discuss IFAP/BRESHECK as one extended entity due to the shared gene. Pediatric Neurology Briefs+1
Causes
Primary cause (core fact):
- BRESEK/BRESHECK and IFAP-with-BRESHECK are caused by disease-causing changes (variants) in MBTPS2, a gene on the X chromosome. MBTPS2 encodes a membrane-bound zinc metalloprotease that activates sterol-regulated transcription factors (SREBP pathway) and helps cells adapt to endoplasmic reticulum (ER) stress. When MBTPS2 does not work properly, multiple developing tissues—skin/hair/teeth (ectoderm), brain, skeleton, eyes/ears, kidneys, and gut nerves—can form abnormally. disorders.eyes.arizona.edu+2PubMed+2
How this single genetic cause explains many findings (mechanisms that “cause” the features):
Disrupted cholesterol/sterol signaling in developing tissues impairs cell membranes and differentiation, a core job of MBTPS2 via SREBP activation. disorders.eyes.arizona.edu
Inadequate ER-stress response makes fragile developing cells (like hair follicles, skin keratinocytes, and certain neurons) more prone to dysfunction. disorders.eyes.arizona.edu
Ectodermal dysplasia (skin, hair, nails, teeth) flows from those sterol/keratinization defects and poor stress responses in ectoderm-derived structures. NCBI
Brain anomalies and severe developmental delay reflect abnormal neurodevelopment during embryogenesis when sterol signaling is critical. (Observed repeatedly in case reports.) onlinelibrary.wiley.com+1
Skeletal malformations (vertebrae, scoliosis, polydactyly) likely arise from disturbed signaling in cartilage/bone patterning. (Consistently reported in patients.) rarediseases.info.nih.gov
Eye anomalies and photophobia are well known in the IFAP/BRESHECK spectrum and relate to ectodermal/ocular surface and retinal pathway changes. NCBI
Hearing loss and ear malformations stem from abnormal morphogenesis of the external/middle/inner ear. (Repeated clinical descriptions.) NCBI
Kidney dysplasia/small kidneys result from disrupted nephron development during organogenesis. rarediseases.info.nih.gov
Hirschsprung disease (when present) reflects failed migration/survival of enteric neural crest cells. Pediatric Neurology Briefs
Cleft palate/cryptorchidism appear in the broader BRESHECK end of the spectrum, underscoring multisystem developmental impact. Pediatric Neurology Briefs
X-linked inheritance explains why most described patients are male; female carriers may be unaffected or mildly affected depending on X-inactivation. (The spectrum is catalogued under X-linked IFAP/BRESHECK.) NCBI+1
Variant-specific effects: different MBTPS2 variants may differentially impair sterol regulation and ER-stress pathways, which likely modifies severity. onlinelibrary.wiley.com
Bottom line: although literature often lists many “features,” the cause is one gene (MBTPS2) with downstream pathways that disturb development in many organs, creating the wide symptom range. PubMed+1
Symptoms and signs
Developmental delay and severe intellectual disability – most children have major delays in motor, speech, and learning abilities due to brain malformations and early neurodevelopmental disruption. rarediseases.info.nih.gov
Brain anomalies – often a thin or malformed corpus callosum and enlarged ventricles are seen on MRI; seizures may occur in some cases. NCBI
Poor growth – many children are small for age with slow weight and height gain. thejns.org
Ectodermal dysplasia – dry, rough, scaly skin (ichthyosis), decreased sweating in some, brittle nails, and abnormal or missing teeth. rarediseases.info.nih.gov
Alopecia or very sparse hair – hair may be thin from birth or fall out early and not regrow. Pediatric Neurology Briefs
Eye problems – small or underdeveloped eyes/optic nerves, light sensitivity (photophobia), and corneal changes are reported; vision can be reduced. NCBI
Hearing loss – often with low-set, large, or abnormally shaped ears; hearing testing may confirm conductive or sensorineural loss. NCBI
Skeletal deformities – vertebral anomalies, scoliosis, and sometimes extra digits (polydactyly). rarediseases.info.nih.gov
Kidney dysplasia or small kidneys – kidneys may be under-formed, which can reduce kidney function over time. rarediseases.info.nih.gov
Hirschsprung disease (subset) – missing gut nerves in the colon cause severe constipation or bowel blockage in infancy. Pediatric Neurology Briefs
Cleft palate (subset) – opening in the roof of the mouth affects feeding and speech until repaired. Pediatric Neurology Briefs
Cryptorchidism (subset) – undescended testes in boys, requiring surgical management. Pediatric Neurology Briefs
Facial differences – may include distinctive craniofacial shape related to bone and soft-tissue development. (Described across reports.) onlinelibrary.wiley.com
Feeding difficulties and poor weight gain – from cleft palate, hypotonia, or neurological challenges. (Noted in case descriptions of this spectrum.) thejns.org
Variable severity – symptoms can differ widely, even within a family; this variability is a hallmark of the MBTPS2 spectrum. NCBI
Diagnostic tests
Because this is a syndromic (multi-system) condition, diagnosis combines careful exam, targeted testing of affected organs, and genetic confirmation.
A) Physical examination (bedside assessment)
1) Comprehensive growth and developmental exam – measures height/weight/head size and checks milestones; large gaps from typical development raise suspicion for a syndromic disorder like BRESEK. rarediseases.info.nih.gov
2) Neurologic exam – looks for tone abnormalities, reflex differences, seizures, and signs consistent with structural brain anomalies described in BRESEK. NCBI
3) Dermatologic and hair exam – documents ichthyosis (dry, scaly skin), alopecia or sparse hair, nail and tooth changes, which fit the ectodermal dysplasia component. rarediseases.info.nih.gov
4) Musculoskeletal exam – checks spine curvature (scoliosis), limb alignment, and digits for polydactyly or other malformations. rarediseases.info.nih.gov
5) ENT/eye exam – inspects ear shape/position, screens hearing, and checks for eye underdevelopment, corneal changes, and light sensitivity. NCBI+1
B) “Manual” or bedside tests and focused evaluations
6) Developmental screening tools – standardized checklists/questionnaires to quantify delays in motor, language, and social domains. (Used widely in syndromic assessment.) General clinical practice; included here to operationalize findings above.
7) Ophthalmoscopy and slit-lamp exam – in-office eye evaluation of the cornea and optic nerve for the ocular features seen in IFAP/BRESHECK spectrum. NCBI
8) Hearing assessments (screening otoscopy + bedside checks) – simple bedside hearing and ear canal inspection guide formal audiology testing if concerns arise. NCBI
9) Abdominal/rectal evaluation when constipation is severe – prompts definitive testing for Hirschsprung disease if indicated (see pathology section). Pediatric Neurology Briefs
10) Genitourinary exam in boys – to detect cryptorchidism (undescended testes), often part of the BRESHECK spectrum. Pediatric Neurology Briefs
C) Laboratory and pathological tests
11) MBTPS2 genetic testing (sequencing with deletion/duplication analysis) – the confirmatory test. Finding a pathogenic or likely pathogenic MBTPS2 variant establishes diagnosis within the IFAP/BRESHECK spectrum that includes BRESEK/BRESHECK. Family testing helps clarify carrier status and inheritance. disorders.eyes.arizona.edu+1
12) Exome/genome sequencing – used when a targeted gene test is negative or when multiple anomalies need a broad search; MBTPS2 variants can be detected on these platforms. onlinelibrary.wiley.com
13) Skin biopsy (selected cases) – may show features of ectodermal dysplasia/ichthyosis; helps rule out other causes of skin findings if the diagnosis is unclear. (Supportive, not specific.) NCBI
14) Rectal suction biopsy (if Hirschsprung is suspected) – looks for absence of ganglion cells; this is the gold standard for diagnosing Hirschsprung disease in the BRESHECK subset. Pediatric Neurology Briefs
15) Kidney function labs (serum creatinine, urinalysis) – monitor renal impact when kidneys are small or malformed. (Supportive surveillance aligned with reported renal involvement.) rarediseases.info.nih.gov
D) Electrodiagnostic and physiological tests
16) Auditory Brainstem Response (ABR) – objective test of hearing pathways; useful when developmental delay limits standard audiometry. Hearing loss is part of the syndrome’s ear involvement. NCBI
17) Visual electrophysiology (e.g., VEP/ERG) – helps quantify visual pathway and retinal function in patients with photophobia/ocular anomalies on the IFAP/BRESHECK spectrum. NCBI
18) EEG (as clinically indicated) – used if seizures or abnormal events suggest cortical irritability in patients with brain malformations. (Tool to assess severity rather than to diagnose the syndrome itself.) NCBI
E) Imaging tests
19) Brain MRI – typically shows the structural anomalies reported in this syndrome (e.g., thin corpus callosum, ventriculomegaly); MRI supports the clinical picture and guides neurologic care. NCBI
20) Renal ultrasound (± additional renal imaging) – checks kidney size/structure for dysplasia or hypoplasia and helps plan follow-up. Spinal X-rays for scoliosis and limb films for limb anomalies are also common when skeletal changes are present. rarediseases.info.nih.gov
Non-pharmacological treatments (therapies & others)
1) Multidisciplinary care plan and care coordinator.
A dedicated coordinator (often a genetics-informed pediatrician) aligns neurology, dermatology, dentistry, audiology, nephrology, ophthalmology, orthopedics, and surgery. This reduces fragmented care, anticipates organ-specific screenings (BP/urinalysis for dysplastic kidneys; hearing/vision checks; dental timelines), and schedules early interventions. In ultra-rare disorders with multi-system needs, this hub-and-spoke model improves access to guideline-based care even without disease-specific trials. rarediseases.info.nih.gov+1
2) Early developmental intervention & special education.
Individualized developmental programs (physiotherapy, occupational therapy, speech-language) start as soon as delays are apparent. For children with intellectual disability and structural brain differences, early therapy maximizes function and supports communication, self-care, and mobility goals. School-age plans include adaptive technologies and individualized education programs, tailored to hearing/vision limits and fine-motor constraints. PubMed+1
3) Speech-language therapy & augmentative/alternative communication (AAC).
If hearing or oral-motor limits impede speech, clinicians add AAC (picture systems, tablets, sign language), which can run in parallel with spoken-language goals. In children using cochlear implants or hearing aids, AAC ensures a fully accessible language pathway and reduces the risk of language deprivation while auditory skills develop. NCBI+1
4) Hearing rehabilitation (newborn screening → hearing aids → cochlear implant candidacy).
Standard pathways screen early, trial amplification for sensorineural loss, and consider cochlear implantation when criteria are met (typically bilateral severe-to-profound loss with limited benefit from hearing aids; candidacy often between 9–24 months). Post-implant auditory-verbal therapy and family education are essential for outcomes. PMC+2NCBI+2
5) Vision care and low-vision aids.
Eye anomalies (optic nerve hypoplasia, structural maldevelopment) require regular pediatric ophthalmology follow-up. Interventions can include refractive correction, amblyopia therapy, tinted lenses for photophobia, and low-vision devices for school and mobility, integrated into education plans. rarediseases.info.nih.gov+1
6) Ectodermal dysplasia skin care & cooling plan.
With hypohidrosis/anhidrosis, overheating risk is real. Families use climate control, cooling vests, water sprays, shade, hydration schedules, and emollient skin care. Dental and hair/nail counseling complement skin routines as part of the ED spectrum. Cleveland Clinic+1
7) Dental and craniofacial rehabilitation.
Hypodontia/anodontia and enamel defects are addressed with staged prosthodontics (removable dentures in childhood, implants/orthodontics later), improving chewing, speech, growth, and self-image. Early dental care (often by age 2–3) and iterative appliance updates support facial development. clinmedjournals.org+2PMC+2
8) Nutrition optimization & feeding support.
Growth monitoring with dietitian support helps counter feeding difficulty or increased caloric needs (e.g., post-surgery, spasticity). Plans may include high-calorie diets, texture modifications, reflux precautions, and micronutrient surveillance for iron and vitamin D. Office of Dietary Supplements+1
9) Bowel program for constipation (with/without Hirschsprung disease history).
Post-pull-through or neurogenic bowel patterns benefit from toileting schedules, fiber/fluid goals, stool diaries, and pelvic-floor coaching. These conservative steps are first-line adjuncts, even when medicines or surgery are involved. Bangladesh Journals Online
10) Orthopedic & physical therapy for skeletal deformities.
Scoliosis, vertebral anomalies, or limb malformations are followed with bracing, orthotics, stretching/strengthening, and mobility aids. Timing of orthopedic surgery is individualized to growth and function. PubMed+1
11) Renal monitoring protocol.
Children with dysplastic/hypoplastic kidneys need annual BP checks, urinalysis for protein, renal ultrasounds as indicated, and CKD risk management. Hypertension is treated per pediatric CKD principles with tight targets (≤50th percentile when feasible). PMC
12) Genetic counseling & family testing.
Because reported cases are X-linked and extremely rare, families benefit from genetic counseling about recurrence risk, carrier testing of relatives, and prenatal/early postnatal options in future pregnancies. PubMed
13) Temperature-safety education & heat-illness prevention.
Caregivers learn early signs of overheating, use scheduled cooling/hydration during hot weather, and coordinate school accommodations (cool rooms, water access, rest breaks) to prevent heat emergencies in hypohidrotic ED. Cleveland Clinic
14) Dermatology routines for xerosis and barrier repair.
Fragrance-free emollients, short lukewarm baths, and gentle cleansers reduce xerosis and eczema-like flares seen in ED, complementing systemic hydration. Ophthalmology may add dry-eye strategies if ocular surface is involved. Medscape
15) Ophthalmic surface care (dry-eye hygiene).
For ocular surface irritation or keratoconjunctivitis sicca, clinicians stage artificial tears, lid hygiene, nighttime ointments, and environment control, escalating to prescription drops if needed. SpringerLink
16) Communication access & educational accommodations.
Schools incorporate FM systems, captioning, preferential seating, lighting control for photophobia, test accommodations, and assistive technology to ensure equitable learning. PMC
17) Psychosocial support & family resources.
Peer groups for ED/hearing loss/CKD and mental-health services help parents and siblings cope and sustain care routines over years. Rare-disease networks also improve access to specialists. Cleveland Clinic
18) Vaccination on schedule.
Routine immunizations (and specific vaccines per comorbidities) protect medically vulnerable children from preventable infections that could worsen renal or neurologic outcomes. rarediseases.info.nih.gov
19) Safety planning around anesthesia & surgery.
Multisystem conditions call for detailed pre-anesthetic planning (airway, temperature control, fluid/renal considerations), especially in craniofacial or GI surgery. Bangladesh Journals Online
20) Transition to adult care.
As adolescents age out of pediatrics, structured transfer to adult neurology, dermatology, audiology, nephrology, and dentistry preserves continuity and surveillance. rarediseases.info.nih.gov
Drug treatments
Important: No medicine is FDA-approved for “BRESEK syndrome.” The drugs below are commonly used to treat associated problems (e.g., seizures, spasticity, constipation, dry eye, rhinitis, reflux, infections, hypertension with renal dysplasia). Doses/timing are individualized by specialists; FDA labels are cited to show approved indications/mechanisms/safety for those problems.
1) Levetiracetam (Keppra / ER levetiracetam).
Used for focal/primary generalized seizures when present. Purpose: reduce seizure frequency; Mechanism: binds SV2A to modulate neurotransmitter release. Typical pediatric dosing is weight-based in divided doses; titration is gradual; monitor mood/behavior. Side effects: somnolence, irritability, dizziness. FDA Access Data+1
2) Valproate (Divalproex sodium; Depakote/ER).
Purpose: broad-spectrum antiseizure; Mechanism: increases brain GABA, modulates Na⁺ channels. Dosed by mg/kg/day with serum level monitoring; caution in females of child-bearing potential (teratogenicity). Side effects: weight gain, tremor, hepatotoxicity, thrombocytopenia. FDA Access Data+2FDA Access Data+2
3) Lamotrigine (Lamictal/XR).
Purpose: focal/generalized seizure control and drop-attack syndromes; Mechanism: voltage-gated Na⁺ channel inhibition; slow titration minimizes rash risk. Side effects: rash (including SJS), dizziness; interactions with estrogen-containing hormones may alter levels. FDA Access Data+2FDA Access Data+2
4) Topiramate (Topamax).
Purpose: adjunct for generalized and focal seizures; Mechanism: Na⁺ channel block, GABA enhancement, AMPA antagonism, carbonic anhydrase inhibition. Watch for cognitive slowing, weight loss, nephrolithiasis, metabolic acidosis; pediatric growth and pregnancy warnings apply. FDA Access Data+2FDA Access Data+2
5) Oxcarbazepine (Trileptal).
Purpose: focal seizures; Mechanism: Na⁺ channel modulation. Side effects: hyponatremia, dizziness, rash; monitor sodium and for cross-reactivity in eslicarbazepine allergy. FDA Access Data+2FDA Access Data+2
6) Diazepam rectal gel / nasal spray (Diastat® / Valtoco®).
Purpose: rescue for prolonged/cluster seizures at home; Mechanism: GABA-A facilitation. Caregivers trained for weight-based dose and re-dosing limits. Side effects: sedation, respiratory depression (caution with other CNS depressants). FDA Access Data+2FDA Access Data+2
7) Baclofen (oral granules/solution; Lyvispah®, Ozobax®).
Purpose: treat spasticity that can coexist with central nervous system anomalies; Mechanism: GABA-B agonist reducing excitatory neurotransmission in the spinal cord. Start low, titrate to effect; abrupt cessation can cause withdrawal. Side effects: drowsiness, weakness, hypotonia. FDA Access Data+1
8) Polyethylene glycol 3350 (PEG).
Purpose: chronic constipation management (including post-Hirschsprung pull-through). Mechanism: osmotic water retention in stool to soften and increase frequency. Dosing is individualized; onset 1–3 days. Side effects: bloating, cramps. FDA Access Data+1
9) Amoxicillin (AMOXIL®).
Purpose: treat common bacterial ENT/urinary infections that may occur in patients with ear anomalies or reflux/UTIs. Mechanism: beta-lactam cell-wall inhibition. Pediatric dosing per infection type; check renal dosing if kidney dysfunction. Side effects: rash, diarrhea. FDA Access Data
10) Fluticasone nasal spray (Flonase®/Veramyst®).
Purpose: allergic rhinitis control to improve nasal airflow/sleep; Mechanism: topical glucocorticoid anti-inflammation. Daily use with proper technique reduces systemic exposure. Side effects: epistaxis, nasal irritation; long-term ocular risks are monitored. FDA Access Data+1
11) Cyclosporine ophthalmic emulsion (Restasis® / Multidose®).
Purpose: increase tear production in inflammatory dry-eye (keratoconjunctivitis sicca) that can accompany ectodermal dysplasia. Mechanism: calcineurin inhibition reduces ocular surface inflammation. Dose: 1 drop OU twice daily. Side effects: burning sensation. FDA Access Data+1
12) Omeprazole (Prilosec®).
Purpose: gastroesophageal reflux symptom control that can complicate feeding/growth. Mechanism: proton-pump inhibition reduces gastric acid; timing: 30–60 minutes before meals. Side effects: headache, diarrhea; long-term use reviewed periodically. FDA Access Data+1
13) Enalapril (Epaned®/Vasotec®) or other ACE inhibitor.
Purpose: treat pediatric hypertension/proteinuria in dysplastic kidneys to protect renal function. Mechanism: RAAS blockade; pediatric oral solution exists. Side effects: cough, hyperkalemia; avoid in pregnancy. FDA Access Data+1
14) Amlodipine (Norvasc®/solutions).
Purpose: second-line/adjunct antihypertensive in CKD kids when ACE inhibitors insufficient/contraindicated. Mechanism: calcium-channel blockade causing vasodilation. Side effects: edema, flushing. FDA Access Data+1
15) Intranasal corticosteroid alternatives (e.g., fluticasone furoate).
Purpose: allergic rhinitis control when standard sprays irritate; Mechanism: local anti-inflammation; Side effects similar to class; technique and adherence drive benefit. FDA Access Data
16) Topical ophthalmic lubricants (non-Rx; label-directed).
Purpose: frequent artificial tears/gel improve ocular comfort and surface protection; used alongside prescription cyclosporine when indicated. Side effects: transient blur. SpringerLink
17) Antibiotics per culture-guided therapy (various labels).
For recurrent otitis media, sinusitis, or UTIs from anatomic variants, clinicians use guideline-concordant agents, dosing carefully in CKD. Stewardship prevents resistance and C. difficile. FDA Access Data
18) Stool softeners/senna derivatives (OTC labeling).
When PEG alone is insufficient, stimulant or softener adjuncts are added short-term with bowel-program coaching, especially in post-surgical constipation. FDA Access Data
19) Antihistamines (various).
For rhinitis/dermatologic itch flares in ED, non-sedating agents are chosen first; sedating options reserved for night symptoms under clinician advice. Medscape
20) Analgesia plans around orthopedic/dental surgeries (acetaminophen/NSAIDs per label).
Weight-based dosing and renal function checks are vital; peri-operative pain plans minimize opioids and protect kidneys. PMC
Dietary molecular supplements
Note: Supplements are not proven to treat BRESEK. They can support general health when deficiencies are present. Use only with clinician/dietitian guidance to avoid interactions or excess.
1) Vitamin D.
Supports bone/mineral health; many children need supplementation due to limited sun exposure or diet. Typical maintenance targets are ~400 IU/day in infants (higher if preterm or if deficiency) and age-appropriate intakes thereafter; clinicians may dose higher to correct deficiency. Excess causes hypercalcemia—avoid self-dosing. Office of Dietary Supplements+2Office of Dietary Supplements+2
2) Iron.
Corrects iron-deficiency anemia that worsens fatigue and development; pediatric RDAs vary by age (e.g., 11 mg/day at 7–12 months, 7 mg/day at 1–3 years). Supplement only after confirmation and with monitoring to prevent overload and GI side effects. Office of Dietary Supplements
3) Omega-3 fatty acids (EPA/DHA).
General cardiometabolic and neurodevelopmental support are discussed in population data; dosing and purity vary. Focus first on fish-based dietary sources; supplements are considered when diet is inadequate and bleeding risk is low. Office of Dietary Supplements
4) Zinc.
Essential for immune function and skin integrity; give only when intake is low or deficiency suspected. Age-specific RDAs apply; excessive zinc can impair copper status. Office of Dietary Supplements+1
5) Biotin (Vitamin B7).
Involved in fatty-acid and glucose metabolism; sometimes suggested for hair/nail issues in ED, but robust evidence is limited. Beware of high-dose biotin interfering with some lab tests (e.g., troponin assays). Office of Dietary Supplements
6) Calcium.
Partnered with vitamin D to optimize bone health in limited mobility or skeletal anomalies; dosing follows age RDAs and total dietary intake accounting. Office of Dietary Supplements
7) Probiotics.
May help stool consistency during constipation management or after antibiotics; strain-specific effects are modest; discuss in CKD/immunocompromise. Bangladesh Journals Online
8) Multivitamin tailored to intake.
Used when selective eating, dental limitations, or chronic illness lower diet quality; choose pediatric formulations avoiding megadoses. Office of Dietary Supplements
9) Fiber supplements (psyllium/partially hydrolyzed guar).
Adjunct to bowel programs to increase stool bulk—introduced gradually with fluids to limit bloating. Bangladesh Journals Online
10) Electrolyte solutions for heat days.
In hypohidrotic ED, planned oral rehydration during hot weather helps prevent heat illness; sugar-free options may be preferable for frequent use. Cleveland Clinic
Drugs as “immunity boosters / regenerative / stem-cell
There are no approved “immunity-boosting” or “stem-cell” drugs for BRESEK. Stem-cell transplants do not target the MBTPS2-related pathway or the multi-system malformations reported in BRESEK/BRESHECK. When families ask about advanced therapies, clinicians usually review supportive strategies (vaccination, nutrition, infection prevention) and specific organ-directed treatments instead. If a clinical trial exploring MBTPS2-linked pathways appears in the future, a genetics center can advise eligibility and risks. PubMed+1
Surgeries (procedures & why they’re done)
1) Hirschsprung disease pull-through (e.g., transanal endorectal pull-through).
Removes aganglionic bowel and restores continence in children with HSCR features in the BRESEK/BRESHECK spectrum. Minimally invasive approaches can be single-stage with favorable short- and medium-term outcomes in many centers. PMC+2SpringerOpen+2
2) Cleft palate repair.
Improves feeding, middle-ear ventilation, and speech resonance in children with clefting variants reported within the wider BRESHECK acronym. Timing aligns with craniofacial guidelines to optimize speech and growth. PubMed
3) Orchiopexy for cryptorchidism.
Brings undescended testis into scrotum to protect fertility potential and ease surveillance—performed typically in the first 6–18 months when present. PubMed
4) Cochlear implantation.
For bilateral severe-to-profound sensorineural hearing loss unresponsive to hearing aids, implants can restore access to sound; outcomes depend on early identification and post-implant therapy. PMC+1
5) Orthopedic correction (e.g., scoliosis surgery).
Address progressive curves or deformities that impair function or pulmonary mechanics, following pediatric orthopedic protocols and growth considerations. NCBI
Prevention & long-term protection points
Keep vaccinations up to date; ask about additional immunizations based on kidney function or ENT surgical history. rarediseases.info.nih.gov
Build and rehearse a seizure action plan if seizures are present (including home rescue therapy). FDA Access Data
Enforce temperature-safety routines in hypohidrotic ED: climate control, cooling gear, hydration plan. Cleveland Clinic
Schedule regular renal surveillance: BP, urinalysis, growth checks; treat pediatric hypertension early. PMC
Early hearing/vision detection and timely amplification/therapy to prevent language and learning delays. PMC
Dental prevention: fluoride, hygiene teaching, early prosthodontic planning to support nutrition/speech. PMC
Skin-barrier care to limit eczema/infection risk; fragrance-free emollients. Medscape
Bowel program adherence after HSCR surgery to prevent constipation/soiling cycles. Bangladesh Journals Online
Safety net for feeding/growth: reflux precautions, dietitian follow-up, iron/vitamin D checks. Office of Dietary Supplements+1
Ongoing genetic counseling for family planning and at-risk relatives. PubMed
When to see doctors urgently
Seek medical attention now for prolonged seizures, new focal neurologic deficits, severe headache with vomiting, fever with lethargy, signs of dehydration or heat illness (hot, dry skin; confusion), urinary symptoms with fever or swelling (possible UTI/CKD decompensation), intractable constipation with abdominal distension (possible obstructive complications), acute hearing/vision loss, or wound/skin infections that spread. These red-flags are common escalation triggers across the organ systems involved in BRESEK. PMC+1
What to eat & what to avoid
Hydration strategy, especially in hot weather; include oral rehydration solutions on heat-risk days. Avoid sugary drinks as “hydration.” Cleveland Clinic
Iron-rich foods (meats, legumes, fortified cereals) with vitamin C sources; limit excessive cow’s milk in toddlers that can worsen iron deficiency. Office of Dietary Supplements
Calcium and vitamin D adequacy for bone health—use dairy or fortified alternatives; supplement only if advised. Office of Dietary Supplements
Texture-appropriate meals if oral-motor or dental issues exist; involve a dietitian for safe weight gain. clinmedjournals.org
Fiber & fluids for stool regularity; introduce fiber gradually to reduce gas/bloating. Bangladesh Journals Online
Limit ultra-processed, high-salt foods to protect blood pressure and kidneys; prefer fresh/frozen whole foods. PMC
Fish twice weekly for dietary omega-3s when safe and culturally acceptable; check bones in young children. Office of Dietary Supplements
Allergen awareness post-cleft repair/dental prosthetics—monitor chewing/swallowing safely while advancing textures. scienceopen.com
Avoid overheating foods/fluids (very hot soups/teas) before outdoor activity; choose cool snacks and water access. Cleveland Clinic
Medication-diet checks (e.g., timing PPIs before meals; sodium load in effervescent meds if hypertensive). Coordinate with your pharmacist. FDA Access Data
Frequently asked questions
1) Is there a cure for BRESEK?
No curative therapy exists. Care targets each organ system to maximize function and quality of life; genetic counseling supports family planning. rarediseases.info.nih.gov+1
2) Is BRESEK always due to MBTPS2?
Most reports linking the BRESEK/BRESHECK/IFAP spectrum implicate MBTPS2, but the original descriptions discussed other possibilities; today, MBTPS2 testing is routine when the phenotype fits. PubMed+1
3) How common is BRESEK?
Extremely rare—only a few published male cases; true prevalence is unknown. PubMed
4) Why is hearing care emphasized?
Because ear anomalies and hearing loss are common, timely amplification/implantation prevents language deprivation and supports cognitive/social development. PMC+1
5) Do children with BRESEK overheat more easily?
Yes, hypohidrotic ED reduces sweating. Families use cooling strategies and hydration plans, especially in hot climates. Cleveland Clinic
6) What is the outlook for kidney function?
Kidney dysplasia/hypoplasia varies. Lifelong monitoring of BP, urine protein, and growth is standard; treating hypertension early protects kidneys. PMC
7) Are seizures guaranteed?
No, but if present they are treated per standard pediatric epilepsy pathways with rescue plans for clusters. FDA Access Data+1
8) Will my child need multiple surgeries?
Only if indicated (e.g., Hirschsprung, cleft palate, orchiopexy, scoliosis, cochlear implant). Timing balances growth, function, and risks. PMC
9) Can dental prosthetics be used in young children?
Yes—early removable dentures/partials are common in ED to support chewing, growth, and speech, evolving to implants later. clinmedjournals.org
10) Are there clinical trials?
Given the rarity, trials are scarce; a genetics center may help identify mechanistic or natural-history studies as they appear. PubMed
11) Are special diets necessary?
No disease-specific diet, but individualized nutrition plans (iron/vitamin D sufficiency, reflux precautions, constipation management) are common. Office of Dietary Supplements+1
12) Do cochlear implants replace speech therapy?
No—implants provide access to sound, but outcomes require intensive therapy; bilingual exposure (spoken plus sign language) supports full language access. NCBI+1
13) Is biotin effective for hair/nail issues in ED?
Evidence is limited; discuss risks/benefits and lab-test interferences before use. Office of Dietary Supplements
14) Can antihypertensive medicines harm kidneys?
ACE inhibitors like enalapril protect kidneys by lowering pressure/proteinuria; clinicians monitor potassium/creatinine and adjust dosing. FDA Access Data
15) What’s the single most important step for families?
Build a written, shared care plan with a coordinator covering heat safety, seizure/ENT/renal plans, therapy schedules, school accommodations, and emergency contacts. rarediseases.info.nih.gov
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: November 02, 2025.
