What is the diagnosis and treatment for a patient with cleft lip, splenomegaly, and small ovaries?

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)

The constellation of cleft lip, splenomegaly, and small ovaries strongly suggests Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome), which requires immediate genetic testing for PTCH1 mutations and referral to a multidisciplinary team for comprehensive evaluation and surveillance. 1

Diagnostic Criteria and Clinical Recognition

The American College of Medical Genetics and Genomics identifies cleft lip or cleft palate as a minor criterion for Nevoid Basal Cell Carcinoma Syndrome, while ovarian fibromas (which can present as small ovaries on imaging) are also listed as a minor criterion 1. The diagnosis requires either:

• Two major criteria, OR
• One major criterion plus two minor criteria 1

Major Criteria Include:

• Lamellar calcification of the falx cerebri in patients younger than age 20 1
• Jaw keratocysts 1
• Palmar or plantar pits 1
• Multiple basal cell carcinomas (>5 lifetime) or one before age 30 1
• First-degree relative with confirmed Gorlin syndrome 1

Additional Minor Criteria to Assess:

• Childhood medulloblastoma 1
• Macrocephaly (occipital frontal circumference >97th percentile) 1
• Vertebral or rib anomalies on x-ray 1
• Polydactyly (preaxial or postaxial) 1
• Cardiac fibromas 1
• Ocular anomalies (cataracts, developmental defects, pigmentary changes) 1

Critical caveat: Splenomegaly is NOT a recognized criterion for Gorlin syndrome, suggesting either a coincidental finding requiring separate workup or the possibility of an alternative diagnosis 1.

Immediate Diagnostic Workup

Genetic Testing

• PTCH1 gene mutation analysis is the definitive diagnostic test 1
• Referral to medical genetics is mandatory for any patient meeting clinical criteria 1

Imaging Studies Required

• Panoramic dental radiographs to evaluate for jaw keratocysts 1
• Brain MRI to assess for falx calcification and rule out medulloblastoma 1
• Pelvic ultrasound to characterize ovarian pathology and assess for fibromas 1
• Skeletal survey to identify rib/vertebral anomalies 1
• Echocardiography to screen for cardiac fibromas 1

Splenomegaly Evaluation

Since splenomegaly is not part of Gorlin syndrome, pursue separate workup:

• Complete blood count with differential 1
• Peripheral blood smear 1
• Abdominal ultrasound or CT to measure spleen size and assess for other pathology 1
• Consider hematology referral if unexplained 1

Management of Cleft Lip

Surgical Approach

• Cleft lip repair should be performed around age 1 year to allow adequate development while minimizing feeding and speech complications 2, 3
• Diagnosis is strictly clinical and does not require radiographic imaging 2, 3
• Comprehensive evaluation by a multidisciplinary cleft/craniofacial team is essential 2, 3

Speech and Language Assessment

• Begin speech/language assessments at 6-18 months of age and continue routinely 2, 3
• Many children require intensive speech therapy throughout childhood 2
• Early implementation of augmentative communication (sign language) may be needed 2

Ongoing Monitoring

• Monitor continuously for otitis media with effusion and hearing loss throughout childhood, even after repair 2, 3
• Tympanostomy tube insertion may be necessary for persistent middle ear effusion 2
• Regular dental follow-up for malocclusions and dental anomalies 4

Management of Ovarian Pathology

If Ovarian Fibromas Confirmed

• Conservative management with surveillance is appropriate for asymptomatic ovarian fibromas in Gorlin syndrome 1
• Serial pelvic ultrasounds every 6-12 months to monitor size 1
• Surgical intervention only if symptomatic (pain, torsion) or rapid growth 1

If Alternative Pathology Suspected

• Sex cord tumors with annular tubules (SCTAT) are specifically associated with Peutz-Jeghers syndrome, not Gorlin syndrome 1
• If malignancy suspected, refer to gynecologic oncology for staging and management 1

Long-Term Surveillance for Gorlin Syndrome

Skin Surveillance

• Dermatologic examination every 6-12 months starting in adolescence 1
• Patient education on sun protection and avoidance of radiation exposure 1
• Early biopsy of suspicious skin lesions 1

Neurologic Surveillance

• Annual neurologic examination during childhood to screen for medulloblastoma 1
• Brain MRI if any concerning neurologic symptoms develop 1

Dental Surveillance

• Panoramic radiographs annually or biannually to monitor for jaw keratocysts 1
• Prompt surgical management of keratocysts when identified 1

Common Pitfalls to Avoid

• Failure to recognize the syndromic nature of cleft lip when associated with other anomalies leads to missed diagnosis of Gorlin syndrome 1
• Inadequate sun protection counseling results in early development of multiple basal cell carcinomas 1
• Overlooking the need for lifelong surveillance, as basal cell carcinomas and jaw keratocysts can develop throughout life 1
• Performing radiation therapy in patients with Gorlin syndrome can trigger aggressive basal cell carcinoma development and should be avoided whenever possible 1
• Failing to provide genetic counseling for family planning, as this is an autosomal dominant condition with 50% transmission risk 1