What is the likely diagnosis and recommended evaluation and management for a child presenting with Stahl’s ear, macrodactyly, and macropenis?

Diagnosis: PIK3CA-Related Overgrowth Spectrum (PROS)

The constellation of Stahl's ear, macrodactyly, and macropenis strongly suggests a PIK3CA-related overgrowth spectrum disorder, requiring immediate genetic testing for somatic PIK3CA mutations and comprehensive evaluation for associated vascular malformations and progressive overgrowth complications.

Clinical Recognition

This presentation represents segmental overgrowth with multiple anatomic sites involved, which is pathognomonic for mosaic overgrowth disorders rather than isolated congenital anomalies:

• Macrodactyly is attributed to somatic mutations in PIK3CA, a component of the mTOR pathway-related overgrowth disorders 1
• Asymmetric and disproportionate overgrowth affecting multiple body regions (digits, genitalia, and ear structures) occurs in 100% of PIK3CA mutation cases, with 89% showing congenital onset 2
• Adipose dysregulation is present in all patients with PIK3CA-related overgrowth spectrum 2

Key Distinguishing Features

The combination of features helps differentiate this from other overgrowth syndromes:

• Absence of cerebriform connective tissue nevi distinguishes PIK3CA-related overgrowth from Proteus syndrome 2
• Congenital onset with asymmetric distribution is characteristic, with overgrowth predominantly affecting lower extremities more than upper extremities in a distal-to-proximal pattern 2
• Vascular malformations occur in 43% of PIK3CA mutation cases, significantly lower than in Proteus syndrome 2

Immediate Diagnostic Evaluation

Genetic Testing (Priority)

• Obtain somatic PIK3CA mutation analysis from affected tissue (not blood), as this is a mosaic disorder requiring tissue from the overgrown area for diagnosis 1, 2
• Document laterality and extent of all overgrown structures, noting that unilateral overgrowth is predominantly left-sided in PIK3CA-related disorders 2

Syndromic Evaluation

Following the ACMG framework for evaluating congenital anomalies, perform systematic screening 3:

• Cardiac evaluation: Echocardiogram to exclude structural defects and assess for vascular malformations 3
• Renal ultrasound: Screen for structural abnormalities including hematuria, proteinuria, and anatomic defects 3
• Ophthalmologic examination: Evaluate for visual anomalies, retinal abnormalities, and early cataracts 3
• Neurologic assessment: Document any focal findings, developmental concerns, or vestibular dysfunction 3
• Vascular imaging: MRI or ultrasound of affected limbs to identify vascular malformations present in 43% of cases 2

Hearing Assessment

Given the ear anomaly (Stahl's ear):

• Audiometric evaluation is mandatory, as craniofacial anomalies involving the pinna are risk indicators for hearing loss 4
• Document specific auricular structures present or absent, including helical rim, antihelix, tragus, antitragus, and external auditory canal patency 4
• Otoscopic examination to exclude middle ear pathology 3

Family and Exposure History

Construct a detailed pedigree addressing 3, 5:

• Three to four generations with attention to consanguinity and similar overgrowth patterns in relatives
• Ethnicity and country of origin for population-specific genetic considerations
• Prenatal exposures: TORCH infections, ototoxic drugs, alcohol, hypoxia, or ECMO 3, 5
• Postnatal infections: Meningitis or other CNS infections 3

Management Algorithm

Surgical Considerations for Macrodactyly

Indications for intervention include 1:

• Peripheral compressive neuropathies (e.g., carpal tunnel syndrome)
• Grotesque enlargement interfering with function
• Psychosocial distress due to deformity
• Macrodystrophic lipomatosis with proximal limb involvement

Surgical options are categorized as 1:

1. Digit reduction: Soft tissue debulking, skeletal shortening/terminalization, Barsky procedure, Tsuge technique
2. Growth limitation: Digital nerve stripping and epiphysiodesis
3. Deviation correction: Wedge osteotomy, arthrodesis, ray resection

Stahl's Ear Correction

If cosmetic or functional concerns arise 6, 7, 8:

• Cartilage scoring and folding technique with creation of a fan-shaped cartilage flap has shown excellent outcomes in 17 patients aged 9-46 years 7
• Timing: Can be performed once cartilage is sufficiently developed, typically after age 6-7 years
• Anatomic consideration: The abnormal insertion of the transverse muscle of the ear may require specific attention during correction 8

Monitoring for Progression

Critical to understand the natural history 2:

• Most patients show mild overgrowth with little postnatal progression
• Severe cases demonstrate progressive overgrowth requiring multiple surgeries
• Marked paucity of adipose tissue in unaffected areas occurs in the most severely affected patients
• Serial measurements of affected structures every 6-12 months during growth periods

Critical Pitfalls to Avoid

• Do not assume isolated anomalies: The combination of features mandates evaluation for systemic involvement 2
• Do not test blood for PIK3CA mutations: This is a somatic mosaic disorder requiring affected tissue for diagnosis 1, 2
• Do not delay vascular imaging: Vascular malformations occur in 43% and may be clinically silent initially 2
• Do not overlook hearing assessment: Ear anomalies are risk indicators requiring audiometric evaluation 4
• Do not confuse with Proteus syndrome: Absence of cerebriform connective tissue nevi and congenital onset distinguish PIK3CA-related overgrowth 2