Cantú Syndrome and Endocrine Monitoring: A Pediatric Case Report

Carlota Aibar-Marco; Sandra Maeso-Méndez; Sonia Heras-Gonzalez; Ignacio Diez-Lopez

doi:10.20944/preprints202608.2048.v1

Submitted:

27 August 2026

Posted:

28 August 2026

You are already at the latest version

Abstract

Introduction: Cantú syndrome, or hypertrichotic osteochondrodysplasia, is a rare genetic disorder characterized by generalized hypertrichosis, macrosomia, cardiomegaly, and distinctive coarse facial features. What is unique about this case is the clinical challenge of distinguishing syndromic hypertrichosis from premature pubarche in early childhood, emphasizing the necessity for multidisciplinary and targeted endocrine monitoring in these patients and contributing to the sparse literature on its long-term management. Main concerns and clinical findings: An 8-year-old girl with Cantú syndrome presented for a growth assessment and evaluation of early body hair development. She exhibited striking generalized hypertrichosis on her legs, back, and face, alongside a complex cardiovascular history and chronic kidney disease. Primary diagnoses, interventions, and outcomes: A thorough physical and endocrinological evaluation revealed normal baseline androgens and elevated SHBG, effectively differentiating her syndromic hypertrichosis from a reversible endocrine imbalance (e.g., premature adrenarche or pubarche). Interventions have been largely observational for her hypertrichosis due to the lack of targeted treatments and complicating comorbidities, while her cardiovascular and renal conditions continue to be managed multidisciplinarily. Conclusion: Cantú syndrome requires a highly individualized approach. Clinicians must remain vigilant for evolving endocrine dysfunctions, particularly regarding growth and pubertal development, while supporting the profound psychosocial burden caused by the currently untreatable hypertrichosis.

Keywords:

Cantú syndrome

;

hypertrichosis

;

pediatric endocrinology

;

ABCC9 gene

;

case report

Subject:

Biology and Life Sciences - Endocrinology and Metabolism

Introduction

Cantú syndrome is a rare autosomal dominant genetic disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. While macrocephaly and coarse facial features may initially suggest a metabolic storage disorder, individuals typically develop a muscular appearance with minimal subcutaneous fat during childhood. Skeletal anomalies frequently include a narrow thorax, broad ribs, coxa valga, osteopenia, and metaphyseal widening of the long bones.

Cardiac involvement is present in approximately 80% of cases and may include patent ductus arteriosus (PDA), ventricular hypertrophy, pulmonary hypertension, and pericardial effusions. A defining and cosmetically challenging hallmark of this syndrome is generalized congenital hypertrichosis. This excessive hair growth often mimics severe hirsutism and can be particularly striking in early childhood.

This case report is unique as it illustrates the clinical dilemma of managing severe syndromic hypertrichosis versus an endocrine abnormality like premature pubarche. Because Cantú syndrome is primarily caused by heterozygous missense mutations in the ABCC9 gene, the hypertrichosis is a genetically driven structural anomaly, rendering standard dermatological or hormonal treatments generally ineffective. This report highlights the vital role of longitudinal endocrine surveillance required for these patients.

Patient Information

De-identified patient-specific information: The patient is a prepubertal female.

Primary concerns and symptoms: She was initially referred from primary care to the Pediatric Endocrinology department for a growth evaluation and assessment of early, generalized body hair development.

Medical, family, and psychosocial history:

-: Mother: 38 years old, height 155 cm, menarche at 9 years; diagnosed with Type 2 Diabetes Mellitus managed with empagliflozin and metformin.
-: Father: 45 years old, height 168 cm; history of obesity and myocardial infarction at 38 years.
-: Siblings: Five sisters. One experienced premature thelarche at age 7 (managed with triptorelin). Another was diagnosed with Immune Thrombocytopenia (ITP) and had menarche at 9 years.
-: Target Height: 155 cm (+/- 6 cm).
-: Gestation and Birth: The pregnancy was complicated by diet-controlled gestational diabetes. Born via spontaneous vaginal delivery at 36 weeks. Birth weight: 3040 g (+0.2 SDS), length: 46.5 cm (-1.5 SDS), head circumference: 34 cm. Apgar: 8/9. Abundant lanugo was noted at birth, leading to an initial suspicion of Cornelia de Lange syndrome.

Relevant past interventions and their outcomes: The patient has a complex cardiovascular history requiring surgical intervention for a PDA, an atrial septal defect (ASD), and an iatrogenic aortic arch obstruction. She also has a small muscular ventricular septal defect (VSD). Secondary to cardiac surgery complications, she developed renal failure and has Chronic Kidney Disease (CKD) stage G2 A1. Additionally, she presented with microcytic hypochromic anemia.

Clinical Findings

Following a loss to follow-up in April 2024, the patient returned to the clinic in June 2026 at the chronological age of 8 years and 4 months. She was in good general condition.

-: Anthropometry: Weight 24.1 kg (-1.2 SDS), Height 120 cm (-1.8 SDS). Bone age (Greulich-Pyle) was 8 years and 10 months. She presented with short stature, though not strictly within the pathological range yet.
-: Pubertal assessment: Tanner stage I for breast development (Thelarche I) and axillary hair (Axillarche I). Pubic hair was staged as Pubarche II-III; however, it was noted that the slightly darker and thicker hair closely resembled the generalized hypertrichosis present on the rest of her body. Clitoral length was normal at 20 mm.
-: Skin/Hair: Striking generalized hypertrichosis was visually documented on her legs (Figure 1), back (Figure 2), and face (Figure 3). No exanthems, petechiae, skin lesions, or palpable goiter were present.

Timeline

Episode of Care Timeline:

-: Gestation (Week 36): Born with normal weight but abundant lanugo; Cornelia de Lange syndrome initially suspected.
-: Infancy/Early Childhood: Genetic testing for Cornelia de Lange was negative. Diagnosed with Cantú syndrome based on phenotype and genetics. Underwent multiple cardiac surgeries (PDA, ASD, aortic arch) and developed CKD.
-: April 2024 (Age ~6 years, 2 months): Initial referral to Pediatric Endocrinology for growth evaluation.
-: June 2026 (Age 8 years, 4 months): Follow-up clinical visit. Severe hypertrichosis noted; pubertal and growth assessment performed; baseline androgens tested to rule out premature pubarche.

Diagnostic Assessment

Diagnostic methods: Physical examination, auxological assessment, bone age X-ray (Greulich-Pyle), and comprehensive endocrinological laboratory testing.

Diagnostic challenges: The primary challenge was differentiating her baseline syndromic generalized hypertrichosis and slightly thickened pubic hair from a potential new onset of premature adrenarche or pubarche.

Diagnosis: Isolated syndromic hypertrichosis secondary to Cantú syndrome, with no concurrent endocrine imbalance. (Initial differential diagnosis of Cornelia de Lange was previously ruled out via genetic study).

Prognostic characteristics: Her baseline androgens (Testosterone 0.10 ng/mL, DHEA-S 3.78 µmol/L, 17-OHP 0.6 ng/mL) and other hormonal levels were within normal prepubertal ranges, effectively ruling out an androgen-excess disorder. SHBG was elevated (150 nmol/L).

Therapeutic Intervention

Types of therapeutic intervention: Historically, the patient required significant surgical interventions for her congenital heart defects. Regarding her hypertrichosis and endocrinological status, the intervention has been strictly observational and preventive.

Administration of therapeutic intervention: Currently on Ibuprofen and Salbutamol as needed. No targeted therapies (pharmacologic or aesthetic) could be safely offered to resolve the hair growth due to her age, the genetic nature of the condition, and her concurrent nephrological status.

Changes in therapeutic interventions: No hormonal therapies (e.g., antiandrogens) were initiated because her androgens were normal, rendering such treatments ineffective for structurally driven hypertrichosis. Furthermore, off-label pediatric use of potential dermatologic drugs was limited by her renal condition.

Follow-up and Outcomes

Clinician- and patient-assessed outcomes: The patient continues to experience significant hypertrichosis, which remains a cosmetically challenging hallmark of the disease. Her growth velocity and pubertal progression are currently stable and appropriately monitored.Important follow-up diagnostic and other test results: The patient will remain under close endocrinological surveillance to monitor growth, as patients with Cantú syndrome are at risk for pituitary hormone deficiencies and growth failure.

Adverse and unanticipated events: No adverse events from the current observational approach.

Discussion

Strengths and limitations in your approach: A major strength of this case is the multidisciplinary approach and the rigorous exclusion of concurrent endocrine disorders (e.g., premature pubarche) in a patient with severe body hair. A limitation is the inability to offer the patient an effective, targeted therapeutic option for her hypertrichosis, which remains a significant psychosocial burden.

Discussion of the relevant medical literature: Cantú syndrome is an exceptionally rare disorder. Emerging evidence suggests the syndrome can encompass complex endocrine abnormalities, including compromised linear growth, partial growth hormone deficiency, and adrenal insufficiency. Pathogenic variants in the ABCC9 and KCNJ8 genes may directly impact glucose-sensing neurons in the hypothalamus, highlighting that growth failure and other endocrine axes can be significantly affected. Furthermore, managing this excessive hair growth presents a formidable challenge. Standard pharmacological treatments for hirsutism are entirely ineffective because the hypertrichosis is driven by a primary genetic channelopathy, not androgen excess.

The rationale for your conclusions: Given the normal androgen profile and the known natural history of Cantú syndrome, we concluded that her hair growth is an untreatable syndromic feature rather than an acute endocrine issue. This warrants supportive care and aesthetic counseling rather than pharmacological suppression.

Cantú syndrome requires a highly individualized, multidisciplinary approach. Clinicians must remain vigilant for evolving endocrine dysfunctions, particularly regarding growth and pubertal development, while also acknowledging and supporting the profound psychosocial burden caused by the currently untreatable hypertrichosis.

Patient Perspective

While the patient is young, her family has expressed significant concern regarding the cosmetic appearance of the generalized hypertrichosis. They understand the limitations of current medical therapies and the genetic nature of the hair growth, relying on multidisciplinary support to manage the psychosocial impact.

Informed Consent: Written informed consent was obtained from the patient’s legal guardians (parents) for participation in the study and for the publication of this case report and any accompanying clinical images. Patient anonymity has been strictly preserved throughout the manuscript.

Table 1. Baseline Endocrinological Blood Test Results and Reference Ranges.

17-hydroxypregnenolone: 1.44 ng/mL (Ref: 0–2.12)

11-deoxycortisol: 3.1 ng/mL (Ref: 0.0–7.2)

Thyrotropin (TSH): 2.39 mU/L (Ref: 0.35–4.94)

Follicle-stimulating hormone (FSH): 6.4 U/L

Estradiol (17β-estradiol, E2): <10 pg/mL

Testosterone: 0.10 ng/mL

Dehydroepiandrosterone sulfate (DHEA-S): 3.78 µmol/L (Ref: 0.08–2.31)

17-hydroxyprogesterone: 0.6 ng/mL (Ref: 0.1–2.9)

Sex hormone-binding globulin (SHBG): 150 nmol/L

Androstenedione (Δ4-androstenedione): 0.3 ng/mL (Ref: 0.1–0.5)

Cortisol: 9.0 µg/dL (Ref: 4.0–20.0)

Adrenocorticotropic hormone (ACTH): 21 pg/mL (Ref: 7–62)

References

Cantu, J. M., Garcia-Cruz, D., Sanchez-Corona, J., Hernandez, A., Nazara, Z. A distinct osteochondrodysplasia with hypertrichosis--individualization of a probable autosomal recessive entity. Hum. Genet. 60: 36-41, 1982.
Garcia-Cruz, D., Sanchez-Corona, J., Nazara, Z., Garcia-Cruz, M. O., Figuera, L. E., Castaneda, V., Cantu, J. M. Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: further delineation of a new genetic syndrome. Am. J. Med. Genet. 69: 138-151, 1997.
Robertson, S. P., Kirk, E., Bernier, F., Brereton, J., Turner, A., Bankier, A. Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: Cantu syndrome. Am. J. Med. Genet. 85: 395-402, 1999.
Scurr, I., Wilson, L., Lees, M., Robertson, S., Kirk, E., Turner, A., Morton, J., Kidd, A., Shashi, V., Stanley, C., Berry, M., Irvine, A. D., Goudie, D., Turner, C., Brewer, C., Smithson, S. Cantu syndrome: report of nine new cases and expansion of the phenotype. Am. J. Med. Genet. 155A: 508-518, 2011.
Lazalde, B., Sanchez-Urbina, R., Nuno-Arana, I., Bitar, W. E., Ramirez-Duenas, M. L. Autosomal dominant inheritance in Cantu syndrome (congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly). Am. J. Med. Genet. 94: 421-427, 2000.
Grange, D. K., Lorch, S. M., Cole, P. L., Singh, G. K. Cantu syndrome in a woman and her two daughters: further confirmation of autosomal dominant inheritance and review of the cardiac manifestation. Am. J. Med. Genet. 140A: 1673-1680, 2006.
van Bon, B. W. M., Gilissen, C., Grange, D. K., Hennekam, R. C. M., Kayserili, H., Engels, H., Reutter, H., Ostergaard, J. R., Morava, E., Tsiakas, K., Isidor, B., Le Merrer, M., and 9 others. Cantu syndrome is caused by mutations in ABCC9. Am. J. Hum. Genet. 90: 1094-1101, 2012.
Harakalova, M., van Harssel, J. J. T., Terhal, P. A., van Lieshout, S., Duran, K., Renkens, I., Amor, D. J., Wilson, L. C., Kirk, E. P., Turner, C. L. S., Shears, D., Garcia-Minaur, S., and 19 others. Dominant missense mutations in ABCC9 cause Cantu syndrome. Nature Genet. 44: 793-796, 2012.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.