Deafness–Pili Torti–Hypogonadism Syndrome

Other names
Types
Causes
Symptoms
Diagnostic tests
Non-pharmacological treatments
Drug treatments
Dietary molecular supplements
Drugs for immunity booster / regenerative / stem-cell
Surgeries / procedures
Preventions (practical)
When to see doctors
Foods to eat and to limit/avoid
Frequently asked questions

Deafness–Pili Torti–Hypogonadism Syndrome is a very rare genetic condition that links three main problems: (1) permanent inner-ear hearing loss (sensorineural deafness), (2) a hair-shaft defect called pili torti that makes scalp hair dry, brittle, and “twisted,” and (3) hypogonadism, meaning the sex glands do not make enough hormones; some patients also have low growth hormone. It has been reported in only a few families and likely follows autosomal recessive inheritance. It overlaps with Björnstad syndrome (pili torti + hearing loss) but adds hypogonadism as a key feature. NCBI+2Genetic & Rare Diseases Info Center+2

Pili torti means the hair shaft is flattened and then twists 180° at uneven intervals; the hair breaks easily, making it short and sparse. Under the microscope the hair looks ribbon-like and spiraled. Pili torti may occur in several rare genetic disorders, and when it appears together with early sensorineural deafness and underactive sex glands, the pattern suggests Crandall syndrome. PubMed+1

In this syndrome, brittle twisted hair reflects a structural hair-shaft abnormality; inner-ear hair cells do not function normally, causing progressive hearing loss; and pituitary–gonadal signaling can be low (LH/FSH and sometimes growth hormone), creating delayed puberty, infertility, or low sex-hormone symptoms. The clinical picture resembles Björnstad syndrome, which is caused by mutations in BCS1L, a mitochondrial assembly factor; while Crandall’s exact gene is not firmly established, the overlap supports mitochondrial/oxidative stress mechanisms affecting hair shafts and cochlear cells. MedlinePlus+2ScienceDirect+2

Crandall syndrome is a very rare condition present from birth. People with this syndrome have three key problems that tend to appear in childhood:

Hearing loss that usually affects both ears and is caused by inner-ear (cochlear) nerve problems (called sensorineural hearing loss).
Pili torti, which means the scalp hair shafts are twisted and fragile under the microscope. Hair breaks easily, looks short, dry, and sparse, and may lead to alopecia (hair loss).
Hypogonadism, which means the sex glands (testes in males, ovaries in females) do not make enough sex hormones. In the original medical description, some patients also had low luteinizing hormone (LH) and low growth hormone (GH).

Doctors consider Crandall syndrome closely related to Björnstad syndrome, which features pili torti + deafness without hypogonadism. Crandall adds the hypogonadism piece. The condition is thought to be autosomal recessive, meaning a child inherits one non-working gene copy from each parent. Because it is so rare, most information comes from case reports and small families. Orpha+2NCBI+2

Other names

Crandall syndrome
Alopecia–deafness–hypogonadism syndrome
Alopecia–sensorineural deafness–hypogonadism syndrome
These all describe the same triad of findings. Orpha

Types

There are no official genetic subtypes yet for Crandall syndrome, because very few families have been described and a single causative gene has not been firmly established. Clinicians sometimes use practical groupings to guide evaluation:

Classic triad: Early-onset sensorineural deafness + pili torti/alopecia + hypogonadism. This matches the original reports. ScienceDirect+1
Overlap with Björnstad-like features: Prominent pili torti with hearing loss, but borderline or late-recognized hypogonadism—emphasizing how Crandall sits on a spectrum with Björnstad syndrome (which is known to be caused by BCS1L gene mutations). Wikipedia+1
Endocrine-dominant: Hypogonadism and possible low GH with milder hair changes and moderate hearing loss—less common but described. NCBI

Note: In Björnstad syndrome, the hair and deafness occur without hypogonadism; it’s linked to BCS1L, a mitochondrial protein, suggesting mitochondrial energy problems may explain hair and ear vulnerability. Crandall may share pathway overlap, but evidence is limited. nejm.org+1

Causes

Because Crandall syndrome is inherited and extremely rare, “causes” are best understood as underlying biological mechanisms and risk situations that make the triad more likely. Each point below describes a plausible, evidence-informed mechanism or risk, stated cautiously because very few families are published.

Autosomal recessive inheritance
When both parents silently carry one non-working copy, a child can receive both and develop the syndrome. This explains the sibling clusters in published families. ScienceDirect+1
Shared pathway with Björnstad syndrome
Björnstad is caused by BCS1L defects that impair mitochondrial energy production; similar pathways could stress hair shafts and cochlear cells in Crandall, though a single gene for Crandall is not confirmed. nejm.org
Mitochondrial energy stress in the inner ear
Cochlear hair cells need high energy. If cell power plants underperform, these cells are damaged, leading to sensorineural hearing loss. (Well-established in Björnstad; Crandall is presumed related.) nejm.org
Structural weakness of hair shafts (pili torti)
Twisted, flattened shafts are fragile and break easily. This is a hallmark feature and may reflect abnormal keratin or cortex organization. PMC
Oxidative stress
In Björnstad, faulty BCS1L may increase reactive oxygen species; similar stress may injure hair and ear cells in Crandall. nejm.org
Hypothalamic–pituitary signaling problems
Original Crandall reports noted low LH and GH, suggesting upstream hormone signaling defects contribute to hypogonadism and growth issues. NCBI
Primary gonadal under-function
Testes or ovaries may not respond fully, producing low sex hormones and delayed puberty.
Microscopic hair-shaft malformation during development
Hair follicle matrix/cortex formation is altered, producing twist/flattening and breakage. PMC
Cochlear development vulnerability in early life
Subtle inner-ear development issues may combine with energy stress to produce early-onset hearing loss. PubMed
Family clustering/consanguinity
When parents are related, recessive conditions are more likely to appear. (General genetics principle applied to rare autosomal recessive disorders.)
Modifier genes
Different background genes may change severity (more alopecia in one person, more endocrine issues in another).
Environmental oxidative stress
Illnesses or exposures that raise oxidative stress could worsen fragile hair and cochlear cells (the underlying vulnerability is genetic, but environment can modulate expression).
Nutritional stress in early childhood
Poor nutrition does not cause the syndrome but may worsen hair fragility and growth problems in a child already genetically predisposed.
Endocrine co-factors
Borderline thyroid dysfunction or growth-factor imbalances could make hair and growth findings more obvious (screening is sensible in evaluation).
Pituitary micro-abnormalities
Some patients show low GH/LH; in theory, subtle pituitary dysfunction may exist (imaging can help if clinically suspected).
Hair-shaft mechanical trauma
Rough grooming or harsh cosmetics do not cause Crandall but can magnify breakage due to pili torti. PMC
Age-related progression
Hearing loss may worsen over time as stressed cochlear cells slowly fail, a pattern seen in related pili torti–deafness syndromes. PubMed
Skin/follicle microcirculation
Speculative: minor blood-flow/structural changes around follicles could amplify hair fragility in genetically susceptible individuals.
Mitochondrial heat sensitivity
Fever or heat stress may transiently worsen hearing in mitochondrial disorders (general principle), potentially relevant here.
Unknown gene(s) yet to be identified
Given how rare Crandall syndrome is, more than one gene could produce the triad; future sequencing may clarify this.

Symptoms

Reduced hearing in both ears
Often noticed in infancy or early childhood. Children may not respond to sounds or have delayed speech. This is inner-ear (sensorineural) hearing loss. PubMed
Fragile, short, and sparse scalp hair
Hair shafts break easily because they are twisted (pili torti). Hair may feel rough, look patchy, and not grow long. PMC
Alopecia (hair loss)
Hair can thin significantly over time, sometimes leaving sparse stubble.
Delayed puberty (boys)
Late testicular enlargement, sparse facial/body hair, voice stays higher pitched longer.
Delayed puberty (girls)
Late breast development and late first period (menarche).
Infertility or reduced fertility
Due to hypogonadism and low sex hormone production.
Short stature or poor growth
If growth hormone is low, height gain can be slower than peers. NCBI
Low energy or reduced exercise tolerance
Not universal, but possible when hormones are low or if there is underlying mitochondrial stress.
Dry, brittle hair texture
Caregivers may notice hair breaks with minimal brushing. PMC
Sun/heat sensitivity of hair
Fragile shafts may feel worse with heat styling or sun exposure.
Speech delay
Secondary to early hearing loss—children may develop speech later without early hearing support. PubMed
Social/learning challenges
Hearing loss can affect classroom learning and social interaction if not supported.
Reduced libido in adolescence/adulthood
Because sex hormone levels are low.
Low bone mineral density risk
Long-term low sex hormones can reduce bone building; screening is prudent.
Psychological impact
Visible hair changes and hearing challenges can affect self-esteem and mood; counseling and peer support help.

Diagnostic tests

A) Physical examination

General pediatric exam with growth charting
Doctors check height, weight, and growth velocity to look for GH-related slowing.
Scalp and hair inspection
They look for short, sparse hair with a rough, “wire-like” feel that breaks easily—suggesting pili torti. PMC
Ear, nose, throat (ENT) exam
Otoscopy rules out earwax or middle-ear fluid (which cause conductive loss), pointing instead to inner-ear (sensorineural) causes as in this syndrome. PubMed
Pubertal staging (Tanner staging)
Assesses breast, genital, and pubic hair development to detect delayed puberty from hypogonadism.
Skin, nails, and eyebrows/eyelashes review
In pili torti syndromes, scalp hair is mainly affected; brows/lashes are usually less involved (helps rule in the pattern). PMC

B) Manual/bedside tests

Bedside hearing screens
Age-appropriate sound screening (e.g., response to calibrated sounds, whisper tests) can flag a problem and prompt full audiology.
Tuning fork tests (Rinne and Weber)
Quick bedside tests help separate sensorineural from conductive loss. Sensorineural patterns support this diagnosis.
Hair “tug” fragility check
Gentle traction shows undue breakage, consistent with pili torti’s brittle shafts. PMC
Functional speech/language observation
Simple bedside assessment of speech progression guides urgency for hearing support.
Clinical pubertal milestones diary
Tracking milestones over months confirms delayed puberty patterns in hypogonadism.

C) Laboratory & pathological tests

Hormone panel (LH, FSH, testosterone/estradiol)
In Crandall, low LH with low sex steroids has been reported, pointing to hypogonadotropic hypogonadism. NCBI
Growth axis testing (IGF-1 ± GH stimulation tests)
Supports suspected growth hormone deficiency described in some patients. NCBI
Thyroid function tests (TSH, free T4)
Helpful to rule out other causes of hair loss and growth delay; thyroid issues can mimic or worsen findings.
Basic metabolic and nutritional labs
Iron, zinc, vitamin D, and complete blood count identify correctable contributors to hair fragility or fatigue (not causal, but relevant to care).
Hair-shaft microscopy (light microscopy)
Shows the diagnostic twisted, flattened segments (pili torti) and explains why hair breaks easily. PMC
(When available) Genetic testing
Panels for pili torti + deafness often include BCS1L (Björnstad). A negative BCS1L result with hypogonadism keeps Crandall on the table; future genes may be found as science advances. nejm.org

D) Electrodiagnostic tests

Pure-tone audiometry
Measures exact hearing thresholds across frequencies and confirms sensorineural loss pattern typical of the syndrome. PubMed
Otoacoustic emissions (OAE)
Checks outer hair-cell function in the cochlea; abnormal results fit sensorineural pathology.
Auditory brainstem response (ABR)
Objective electrical test (useful in infants) that maps the hearing pathway from ear to brainstem.
Bone-conduction audiometry
Distinguishes sensorineural from conductive loss by bypassing the middle ear.

E) Imaging tests (additional helpful studies)

Temporal bone (inner-ear) MRI/CT: Looks for structural ear differences if hearing loss is severe or asymmetric.
Pituitary MRI: Considered if labs suggest pituitary hormone deficiency (LH/GH) to check for structural causes.
Pelvic/testicular ultrasound: Can assess gonadal development if clinically needed.

Non-pharmacological treatments

Comprehensive genetic counseling
Description: A genetic counselor explains inheritance (likely autosomal recessive), recurrence risk (25% when both parents are carriers), and options for family planning. They review what is known—and unknown—about the gene(s) involved and discuss testing panels that cover overlapping syndromes (e.g., Björnstad). Counseling also covers psychosocial support, school accommodations for hearing loss, and how to share results with relatives. When appropriate in local settings, counselors discuss prenatal or preimplantation options. Purpose: empower families with clear risk information and connect them to services. Mechanism: education and risk assessment reduce uncertainty and enable early supports for hearing and endocrine health. NCBI+1
Early audiology + communication plan
Description: A pediatric or adult audiologist measures hearing, fits hearing aids if useful, and sets a long-term follow-up plan. Children get speech-language therapy and classroom supports (FM systems, seating). Where hearing loss is severe, families meet a cochlear-implant team early to learn candidacy and outcomes. Purpose: maximize language, learning, and social development. Mechanism: assistive amplification and therapy compensate for cochlear hair-cell failure and improve auditory input to the brain. PubMed
Cochlear-implant evaluation (when criteria met)
Description: For severe-to-profound sensorineural loss not helped by hearing aids, a cochlear-implant team evaluates candidacy with audiometry, imaging, and speech testing. Education covers expectations, surgical risks, and mapping/rehab after surgery. Purpose: restore access to sound to support language and quality of life. Mechanism: the implant bypasses damaged hair cells and directly stimulates the auditory nerve. PubMed
Bone-anchored hearing system (selected)
Description: For those who cannot benefit from traditional aids or as a complement in mixed patterns, centers may consider bone-anchored devices. Purpose: improve hearing by sending sound through bone conduction. Mechanism: vibratory transmission to the cochlea via skull bone. PubMed
Gentle hair care program
Description: Avoid heat styling, tight hairstyles, harsh chemicals, and vigorous brushing; use wide-tooth combs, mild shampoos/conditioners, and protective styles. Dermatologists sometimes recommend leave-in conditioners and minimizing friction (silk pillowcases). Purpose: reduce breakage in brittle, twisted hair shafts. Mechanism: decreases mechanical stress on hair that is structurally weak from pili torti. PubMed
Dermatology-led monitoring
Description: Periodic exams and trichoscopy monitor hair density and shaft breakage; clinicians review nutrition, thyroid, and iron/B12/folate/zinc/vitamin D labs. Purpose: optimize modifiable factors that worsen hair fragility. Mechanism: correcting deficiencies improves hair cycling and reduces added stress on abnormal shafts. Office of Dietary Supplements+3Office of Dietary Supplements+3Office of Dietary Supplements+3
Endocrinology care plan
Description: Adolescents and adults with delayed puberty or low sex hormones see endocrinology for staged induction of puberty and long-term hormone maintenance, plus bone-health support (calcium/vitamin D, activity). Purpose: normalize secondary sex characteristics, mood, energy, and bone density. Mechanism: physiologic hormone replacement substitutes for deficient gonadal output. NCBI
Fertility counseling & ART options
Description: For people desiring children, reproductive endocrinology discusses gonadotropin therapy and assisted reproduction (e.g., FSH/LH and hCG protocols), with clear explanation of monitoring and risks (e.g., OHSS, multiples). Purpose: support family-building. Mechanism: exogenous FSH/LH stimulate follicle/sperm development; hCG triggers ovulation. FDA Access Data+2FDA Access Data+2
Speech-language therapy (children)
Description: Targeted therapy improves articulation, listening strategies, and classroom communication; parents receive home-practice plans. Purpose: close speech/language gaps from early hearing loss. Mechanism: structured auditory-verbal input and language practice enhance neuroplasticity. PubMed
Educational accommodations
Description: Preferential seating, captioning, FM/remote-microphone systems, and teacher training. Purpose: reduce listening fatigue and improve learning. Mechanism: improves signal-to-noise ratio and language access. PubMed
Psychosocial support
Description: Counseling and peer groups address body image (hair), communication barriers, and fertility stress. Purpose: improve coping and quality of life. Mechanism: social support and coping skills reduce anxiety/depression burden. NCBI
Protective listening habits
Description: Avoid loud noise, use hearing protection, and manage ototoxic medication exposures when alternatives exist. Purpose: preserve remaining hearing. Mechanism: lowers additional cochlear damage on top of genetic loss. PubMed
Bone health program
Description: Weight-bearing exercise, calcium and vitamin D as needed, and monitoring for low bone density if sex hormones are low. Purpose: prevent osteoporosis during hypogonadism. Mechanism: supports bone remodeling and mineralization. Office of Dietary Supplements
Nutrition optimization
Description: Balanced protein, iron, B12, folate, zinc, and omega-3s; correct deficiencies with diet or supplements when clinically indicated. Purpose: support hair and overall health. Mechanism: cofactors for keratin, DNA synthesis, and anti-oxidant defense. Office of Dietary Supplements+3Office of Dietary Supplements+3Office of Dietary Supplements+3
Regular endocrine follow-up
Description: Track symptoms, labs, dose adjustments, and long-term risks (lipids, hematocrit on testosterone; endometrium with estrogen/progestin). Purpose: safe, effective hormone care. Mechanism: surveillance prevents under- or overtreatment. FDA Access Data+1
Dermatologic camouflage & styling
Description: Low-traction styles, fibers/sprays, and gentle wigs if desired. Purpose: improve appearance and confidence while protecting hair. Mechanism: noninvasive cover reduces breakage. PubMed
Vaccination up-to-date
Description: Routine immunizations protect general health; no special vaccine is required for this syndrome, but hearing-impaired children especially benefit from preventing infections that could further affect development. Purpose: reduce preventable illness. Mechanism: immune priming lowers infection risk. NCBI
Safe-home sound environment
Description: Reduce echo/noise at home/class (carpet, curtains), use visual alerts and captioning. Purpose: ease daily communication. Mechanism: improves auditory signal processing. PubMed
Family screening awareness
Description: Inform relatives about the pattern and option for carrier testing when available. Purpose: early detection/support in extended family. Mechanism: cascade information helps future pregnancies. NCBI
Regular multidisciplinary clinic
Description: Coordinate dermatology, audiology, endocrinology, genetics, and psychology. Purpose: integrated, person-centered care plan. Mechanism: reduces gaps and improves outcomes across hair, hearing, and hormones. NCBI

Drug treatments

Important: No drug cures the genetic basis of Crandall syndrome. Medicines target components—hypogonadism and (when present) growth hormone deficiency, and they support fertility planning. Always use FDA labels and clinician guidance.

Testosterone cypionate injection (e.g., Depo-Testosterone) – Androgen
Dose/Time: Typical adult replacement 50–100 mg IM weekly or 100–200 mg every 2 weeks; individualized to keep trough testosterone in mid-normal range. Purpose: Induce/maintain male secondary sex traits, energy, libido, and bone/muscle mass when hypogonadism is present. Mechanism: Replaces deficient testosterone; negative feedback suppresses LH/FSH. Side effects: Acne, oily skin, mood changes, erythrocytosis (↑hematocrit), edema; avoid in prostate/breast cancer; monitor lipids, hematocrit, PSA per label. FDA Access Data
Testosterone gel (AndroGel 1%) – Androgen, transdermal
Dose/Time: Daily application to clean, dry skin of shoulders/upper arms/abdomen; titrate to target serum testosterone. Purpose: Steady physiologic testosterone without injections. Mechanism: Transdermal absorption provides sustained serum levels. Side effects: Skin irritation; risk of secondary exposure to others (cover site); similar systemic androgen effects. FDA Access Data
Testosterone transdermal system (Androderm) – Androgen patch
Dose/Time: Commonly 4–6 mg testosterone delivered over 24 h; applied nightly to back, abdomen, upper arms, or thighs; rotate sites. Purpose/Mechanism: Same as above; delivers stable testosterone via skin. Side effects: Application-site reactions, pruritus; usual androgen risks/monitoring. FDA Access Data
Testosterone undecanoate (AVEED) IM – Long-acting androgen
Dose/Time: 750 mg IM at week 0, week 4, then every 10 weeks (clinic-administered). Purpose: Long-interval maintenance in adult male hypogonadism when injection visits are feasible. Mechanism: Depot ester slowly releases testosterone. Side effects: Pulmonary oil microembolism (post-injection monitoring), anaphylaxis risk; androgen class effects. FDA Access Data+1
Estradiol transdermal system (e.g., VIVELLE-DOT) – Estrogen replacement
Dose/Time: Patch changed twice weekly, dose individualized. In people with a uterus, combine with progesterone to protect endometrium. Purpose: Induce/maintain female secondary sex traits, support bone/vascular health in hypogonadism. Mechanism: Replaces estradiol. Side effects: Nausea, breast tenderness; boxed warnings (VTE, stroke, cancer risks) require careful selection and monitoring. FDA Access Data
Estradiol valerate injection (Delestrogen) – Parenteral estrogen
Dose/Time: IM dosing individualized; used when transdermal/oral routes are unsuitable. Purpose/Mechanism: Systemic estradiol replacement for female hypogonadism. Side effects: As with estrogens; follow boxed warnings and contraindications. FDA Access Data+1
Progesterone (Prometrium) oral – Progestin (natural)
Dose/Time: Commonly 200 mg daily for 12–14 days/month (with cyclic estrogen) or per label. Purpose: Endometrial protection in individuals with a uterus receiving estrogen; may regulate bleeding. Mechanism: Secretory transformation of endometrium. Side effects: Drowsiness, dizziness; peanut-oil content cautions. FDA Access Data
Somatropin (GENOTROPIN) – Recombinant growth hormone
Dose/Time: Weight-based daily SC dosing; titrate by IGF-1 and clinical response. Purpose: Treat documented GH deficiency sometimes reported in Crandall syndrome. Mechanism: Replaces GH to improve linear growth (children) and body composition/bone (adults with deficiency). Side effects: Edema, arthralgia, glucose intolerance; Prader-Willi–specific warnings in label. FDA Access Data
Somatropin (Norditropin) – Recombinant GH pen
Dose/Time: Daily SC; patient-friendly pen devices. Purpose/Mechanism/Monitoring: as above. Side effects: As above; stop for active malignancy; monitor for sleep-apnea/airway issues per label. FDA Access Data
Follitropin alfa (GONAL-F / GONAL-F RFF) – Recombinant FSH
Dose/Time: SC injections under specialist supervision; lowest effective dose with ultrasound/estradiol monitoring. Purpose: Induce follicular development in females with hypogonadotropic hypogonadism; part of ART; also used with hCG in males for spermatogenesis. Mechanism: Direct ovarian/testicular stimulation via FSH receptors. Side effects: OHSS, multiple gestation, injection-site reactions. FDA Access Data+1
Follitropin beta (Follistim AQ) – Recombinant FSH
Dose/Time: SC dosing varies by protocol; in males often ~450 IU/week with hCG after normalizing testosterone. Purpose/Mechanism: same as above. Side effects: OHSS risk in females; injection reactions. FDA Access Data
Menotropins (Menopur/Repronex) – Human menopausal gonadotropins (FSH/LH)
Dose/Time: SC/IM per protocol with careful monitoring; usually followed by hCG trigger. Purpose: Provide both FSH and LH activity for follicle growth. Mechanism: Direct gonadal stimulation. Side effects: OHSS, multiple gestation, local reactions. FDA Access Data+1
Chorionic gonadotropin (hCG) – Pregnyl – LH analogue
Dose/Time: Typical 5,000–10,000 IU IM once to trigger ovulation in women after adequate follicular growth, or regular dosing in men to stimulate Leydig cells for testosterone and spermatogenesis. Purpose: Final oocyte maturation/ovulation or support spermatogenesis. Mechanism: Activates LH receptor. Side effects: Injection pain, gynecomastia (men), OHSS risk (women). FDA Access Data
Choriogonadotropin alfa (Ovidrel) – Recombinant hCG
Dose/Time: 250 mcg SC once as ovulation trigger in ART protocols. Purpose/Mechanism: same as urinary hCG with recombinant product. Side effects: Similar to hCG; avoid if ovaries are over-enlarged at cycle end. FDA Access Data+1
Estradiol transdermal (alternative brands/strengths) – Estrogen replacement
Dose/Time: Twice-weekly patches at individualized doses. Purpose: For female hypogonadism when oral estrogen is not desired. Mechanism/Side effects: as in #5; adhere to boxed warnings and contraindications. FDA Access Data
Testosterone cypionate (multi-source) – Androgen
Comment: Multiple FDA-labeled products exist; dosing/monitoring same as #1; listed separately because many centers use generic single-use vials with clinic protocols. Purpose/Mechanism/Side effects: as in #1. FDA Access Data
Estradiol valerate (Delestrogen) – hypoestrogenism due to hypogonadism
Note: Label explicitly includes this indication. Dose/Time: IM at intervals set by symptom control and levels. Purpose/Mechanism/risks: as in #6. FDA Access Data
Progesterone (Prometrium) – adjunct to estrogen
Dose/Time: Cyclic or continuous per endometrial protection need. Purpose: Reduce risk of estrogen-induced endometrial hyperplasia in people with a uterus. Mechanism/risks: as in #7. FDA Access Data
Follistim AQ (male fertility regimen) – FSH for spermatogenesis
Dose/Time: After testosterone normalized with hCG, add FSH ~450 IU/week divided doses. Purpose/Mechanism/risks: stimulate Sertoli cells; monitor semen analysis and labs. FDA Access Data
Menotropins (Repronex) – historical brand information
Dose/Time: Per protocol with ultrasound and estradiol monitoring; followed by hCG. Purpose/Mechanism/risks: combination FSH/LH stimulation; OHSS and multiple-gestation warnings. FDA Access Data

Hearing loss note: There is no FDA-approved medication that reverses congenital sensorineural hearing loss in this syndrome; management is audiology- and device-centered. PubMed

Dietary molecular supplements

Always talk with your clinician before starting supplements. Doses below are common adult ranges, not personal medical advice.

Vitamin D — Dose: 800–2000 IU/day typical maintenance (adjust by level). Function: supports bone health, immune balance, and muscle function, which is important when sex hormones are low. Mechanism: active vitamin D increases intestinal calcium absorption and influences bone remodeling; correcting deficiency helps reduce bone loss during hypogonadism. Notes: avoid excess—high levels can cause hypercalcemia. Office of Dietary Supplements
Iron (if deficient) — Dose: often 18–65 mg elemental iron/day short-term; confirm deficiency first. Function: supports hair growth and energy. Mechanism: required for hemoglobin and many enzymes in hair follicles; deficiency can worsen hair shedding and fatigue. Notes: GI upset/constipation are common; keep away from children. Office of Dietary Supplements
Folate (vitamin B9) — Dose: 400–800 mcg/day (higher in deficiency per clinician). Function: DNA synthesis and cell division for hair matrix and general health. Mechanism: tetrahydrofolate coenzymes drive nucleotide synthesis and methylation reactions. Notes: correct B12 first to avoid masking neuropathy. Office of Dietary Supplements
Vitamin B12 — Dose: 250–1000 mcg/day oral (or prescribed injections if malabsorption). Function: supports red blood cells and neurologic health; low B12 can worsen fatigue and hair quality. Mechanism: cofactor for methionine synthase and methylmalonyl-CoA mutase. Office of Dietary Supplements
Zinc — Dose: 8–15 mg/day typical; avoid >40 mg/day long-term. Function: keratin formation and immune function. Mechanism: cofactor for many enzymes in hair and skin; deficiency impairs hair structure. Notes: excess zinc can lower copper levels. Office of Dietary Supplements
Omega-3 fatty acids (EPA/DHA) — Dose: 1–2 g/day combined EPA+DHA commonly used for general health. Function: anti-inflammatory support for skin/scalp and cardiovascular health. Mechanism: alters eicosanoid signaling and membrane fluidity; may support follicle environment. Office of Dietary Supplements
Selenium — Dose: ~55 mcg/day (do not exceed 200 mcg/day without advice). Function: antioxidant selenoproteins (e.g., glutathione peroxidases) protect follicles and endocrine tissues. Mechanism: reduces oxidative stress, a suspected factor in hair/ear vulnerability. Notes: excess causes hair loss—stay within safe limits. Office of Dietary Supplements
Coenzyme Q10 — Dose: 100–200 mg/day commonly used. Function: mitochondrial electron-transport cofactor; supports cellular energy and antioxidant defense. Mechanism: shuttles electrons in oxidative phosphorylation; may counter oxidative stress seen in related conditions. Evidence: widely studied but not FDA-approved for specific indications. NCCIH+1
N-acetylcysteine (NAC) — Dose: 600–1200 mg/day is common supplement range. Function: glutathione precursor and antioxidant. Mechanism: supplies cysteine for glutathione, reducing oxidative damage; FDA-approved for other uses, but here considered adjunctive only. Caution: discuss with clinician; interactions and GI side effects possible. PMC+1
Biotin — Dose: 30–100 mcg/day is the RDA level; mega-dosing is not evidence-based for normal biotin status. Function: cofactor for carboxylases in fatty-acid and energy metabolism. Mechanism: supports keratin infrastructure; only helps hair when deficiency exists. Caution: high-dose biotin can interfere with lab tests. Office of Dietary Supplements

Drugs for immunity booster / regenerative / stem-cell

Key safety message: There are no FDA-approved “immunity booster,” regenerative, or stem-cell drugs for Crandall syndrome. The items below are contextual or supportive and must be clinician-directed.

Somatropin (rhGH)—in documented GH deficiency, GH improves growth/body composition. Dose daily SC; monitor IGF-1, glucose, edema. Mechanism: anabolic effects via IGF-1; not disease-curing. FDA Access Data
Physiologic sex-hormone replacement (estradiol/testosterone)—restores secondary sex traits, bone health, and well-being in hypogonadism; dose per labels. Mechanism: replaces missing hormones; not regenerative therapy. FDA Access Data+1
FSH/LH (follitropins/menotropins) with hCG—for fertility induction; specialist-only protocols. Mechanism: stimulates gametogenesis; not general “immune boosters.” FDA Access Data+2FDA Access Data+2
Coenzyme Q10 (supplement)—mitochondrial cofactor/antioxidant; adjunct only; 100–200 mg/day commonly used. Mechanism: supports oxidative phosphorylation; evidence mixed. NCCIH
N-acetylcysteine (supplement/medication)—glutathione precursor; antioxidant support; typical 600–1200 mg/day supplement dosing. Mechanism: replenishes GSH pools; FDA-approved for other indications (acetaminophen overdose, mucolytic). NCBI
Stem-cell therapies—not approved for this condition. Outside clinical trials, stem-cell injections for hair/hearing are unproven and may be unsafe. Prefer regulated trials only. Mechanism: investigational. NCBI

Surgeries / procedures

Cochlear implantation—places an electrode in the cochlea and an external processor. Why: for severe-to-profound sensorineural hearing loss when hearing aids give little benefit. PubMed
Bone-anchored hearing system (BAHS)—titanium implant transmits sound via bone. Why: for selected patterns where bone-conduction routing helps or as an alternative to air-conduction aids. PubMed
Hearing-aid fitting and earmold procedures—not surgery, but technical fittings. Why: to optimize amplification and speech access. PubMed
Endocrine procedure planning—generally no surgery is needed for hypogonadism; treatment is medical. Imaging (pituitary MRI) is a diagnostic step when central causes suspected. Why: to direct medical therapy. NCBI
Cosmetic hair options (medical wigs)—non-surgical, but sometimes part of care. Why: to manage appearance while protecting fragile hair. PubMed

Preventions (practical)

Genetic counseling for family planning. NCBI
Early newborn/child hearing screening and prompt audiology follow-up. PubMed
Avoid loud noise and ototoxic drugs when alternatives exist. PubMed
Gentle hair care; avoid heat/chemicals/tight styles. PubMed
Correct iron, B12, folate, zinc, vitamin D deficiencies. Office of Dietary Supplements+3Office of Dietary Supplements+3Office of Dietary Supplements+3
Maintain bone health (weight-bearing activity + adequate calcium/vitamin D). Office of Dietary Supplements
Regular endocrine and audiology visits for dose/device adjustments. FDA Access Data+1
Classroom and workplace accommodations to reduce listening strain. PubMed
Vaccinations up-to-date to prevent illnesses that could disrupt development. NCBI
Family awareness and early sibling checks for hair/hearing changes. ScienceDirect

When to see doctors

Seek medical care early if a child shows poor startle to sound, delayed speech, or frequent “what?” questions; get audiology promptly. See dermatology if hair breaks easily or is very sparse. Book endocrinology if puberty is delayed, periods are absent/irregular, libido is low, or fertility is a goal. Adults on hormone therapy need regular labs (testosterone/estradiol, hematocrit, lipids) and risk reviews. Urgently re-check if new dizziness, sudden hearing changes, severe headaches, leg swelling, chest pain, or concerning mood changes occur on therapy. PubMed+2FDA Access Data+2

Foods to eat and to limit/avoid

Eat more of:

Lean proteins (eggs, fish, legumes) for hair keratin and general growth. Office of Dietary Supplements
Iron-rich foods (lean red meat, beans, spinach) with vitamin C for absorption. Office of Dietary Supplements
Zinc sources (seafood, beef, pumpkin seeds). Office of Dietary Supplements
Omega-3 fish (salmon, sardines, mackerel). Office of Dietary Supplements
B-vitamins (leafy greens for folate; dairy/animal foods for B12). Office of Dietary Supplements+1

Limit/avoid:

Excess alcohol (hormone and bone impacts). Office of Dietary Supplements
Very high selenium supplements (can cause hair loss). Office of Dietary Supplements
Megadose biotin that can skew lab tests. Office of Dietary Supplements
Ultra-processed, high-salt foods (cardiometabolic risk while on hormones). FDA Access Data
Unregulated “stem-cell” or “hair miracle” products sold online—unsafe and unproven. NCBI

Frequently asked questions

Is there a cure? No. Care focuses on hearing support, gentle hair care, and hormone replacement when needed. NCBI
Will hearing get worse? It can be progressive; regular audiology follow-up helps plan devices or cochlear implants. PubMed
Can medicines fix the hair? No drug fixes pili torti; careful hair practices reduce breakage. PubMed
Can children develop normally? With early hearing support and speech therapy, development improves markedly. PubMed
Do boys and girls both get hypogonadism? Yes—sex hormones can be low in any sex; treatment is individualized. NCBI
Is it the same as Björnstad syndrome? It overlaps but Crandall adds hypogonadism; Björnstad is linked to BCS1L. Wikipedia+1
Which gene causes Crandall? The exact gene is uncertain; Björnstad’s BCS1L highlights mitochondrial mechanisms that may be relevant. Harvard Medical School
Can diet help? Diet can correct deficiencies (iron, B12, folate, zinc, vitamin D) that worsen hair and energy, but it does not cure the syndrome. Office of Dietary Supplements+3Office of Dietary Supplements+3Office of Dietary Supplements+3
Are “hair vitamins” safe? Use only needed doses; high biotin can distort lab tests used to monitor therapy. Office of Dietary Supplements
Is hormone therapy lifelong? Often yes, with regular safety monitoring and dose adjustments. FDA Access Data+1
Can I have children? Many people can with specialist help (FSH/LH + hCG protocols and ART). FDA Access Data+1
Is stem-cell therapy available? Not approved for this condition; consider only regulated clinical trials. NCBI
Does GH help adults? Only if true GH deficiency is proven; benefits and risks must be weighed. FDA Access Data
Will hair transplantation help? Usually not helpful for pili torti because the shaft defect persists. Gentle care is preferred. PubMed
What is the most important first step after diagnosis? Build a team plan: audiology + endocrinology + dermatology + genetics. NCBI

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