What syndromes are associated with a pre‑auricular pit, cleft palate, and penoscrotal fusion?

Syndromes Associated with Preauricular Pit, Cleft Palate, and Penoscrotal Fusion

The constellation of preauricular pit, cleft palate, and penoscrotal fusion strongly suggests CHARGE syndrome, which should be the primary diagnostic consideration and warrants immediate comprehensive evaluation including CHD7 genetic testing. 1

Primary Syndrome: CHARGE

CHARGE syndrome is the most likely diagnosis when these three features occur together. The acronym stands for: Coloboma, Heart defects, Atresia choanae, Retardation (growth and development), Genital abnormalities, and Ear abnormalities. 2

Key Diagnostic Features Present in This Case:

• Ear abnormalities: Preauricular pits are specifically documented as part of the CHARGE phenotype 2, and external ear anomalies including preauricular tags/pits are reported manifestations 2
• Cleft palate: This is a recognized midline craniofacial defect within the CHARGE spectrum 2
• Genital abnormalities: Penoscrotal fusion represents the type of genitourinary malformation characteristic of CHARGE 1

Immediate Diagnostic Workup:

Genetic testing with CHD7 gene sequencing should be ordered as the first-line test, with approximately 60% of CHARGE cases showing positive results. 1

Additional urgent evaluations required:

• Ophthalmologic examination to assess for coloboma, a cardinal CHARGE feature 1
• Comprehensive audiologic testing to document hearing loss type and severity, as dual sensory impairment is common 1
• Cardiac evaluation to identify life-threatening cardiovascular malformations, especially critical in the first year of life 1
• Renal ultrasound to screen for associated genitourinary anomalies 1
• Head MRI to assess for semicircular canal abnormalities and neurological involvement 1

Alternative Consideration: 22q11.2 Deletion Syndrome (DiGeorge Syndrome)

While less likely given the specific triad, 22q11.2 deletion syndrome should be considered as it shares some overlapping features:

• Cleft palate is well-documented, with velopharyngeal insufficiency being common 2
• Ear abnormalities including preauricular tags/pits have been reported 2
• Characteristic facial features include hypertelorism, low-set and abnormally shaped ears 2

However, penoscrotal fusion is not a typical feature of 22q11.2 deletion syndrome, making CHARGE the more likely diagnosis. 2

If 22q11.2 Deletion is Suspected:

• Genetic testing for 22q11.2 deletion via chromosomal microarray or FISH
• Evaluation for thymic hypoplasia, cardiovascular defects, and hypoparathyroidism 2
• Assessment for immunodeficiency with periodic immunologic re-evaluation 2

Critical Management Priorities

Regardless of which syndrome is confirmed:

• Hearing assessment and early intervention are essential, with consideration for early amplification or cochlear implantation planning to address dual sensory impairment risk 1
• Multidisciplinary coordination involving otolaryngology, cardiology, ophthalmology, genetics, developmental pediatrics, and endocrinology 1
• Airway evaluation as both syndromes can have associated airway anomalies 2
• Speech-language assessment beginning at 6-18 months with routine follow-up, as cleft palate significantly impacts speech development 3

Common Pitfalls to Avoid

• Failing to recognize the syndromic nature of these findings and treating them as isolated anomalies rather than pursuing comprehensive genetic evaluation
• Delaying cardiac evaluation, which could miss life-threatening cardiovascular malformations that require urgent intervention 1
• Inadequate hearing assessment, leading to missed opportunities for early intervention during critical language development periods 1
• Not screening for associated conditions such as choanal atresia in CHARGE, which can present as a neonatal respiratory emergency 2