What is the likely diagnosis and recommended evaluation and management for a patient with brachydactyly, dysmorphic facial features, short stature, sparse scalp hair, and trichotillomania?

Trichorhinophalangeal Syndrome Type I (TRPS I)

The constellation of brachydactyly, dysmorphic facial features, short stature, and sparse scalp hair strongly suggests Trichorhinophalangeal Syndrome Type I (TRPS I), which requires molecular confirmation via TRPS1 gene sequencing and coordinated multidisciplinary management. 1, 2

Clinical Diagnosis

TRPS I is a rare autosomal dominant disorder caused by mutations in the TRPS1 gene located at 8q24.12. 1, 2 The clinical phenotype includes:

Characteristic Facial Features

• Sparse, thin, slow-growing scalp hair 1, 2
• Laterally sparse eyebrows 2
• Bulbous "pear-shaped" nose 1, 2
• Elongated and flat philtrum 1, 2
• Thin upper vermillion border 1, 2
• Prominent/protruding ears 1, 3
• Micrognathia and dental anomalies 1

Skeletal Abnormalities

• Brachydactyly with shortening of phalanges and metacarpals 1, 2
• Clinodactyly 1
• Cone-shaped epiphyses (pathognomonic finding on radiographs) 2, 4
• Short stature 1, 2
• Perthes-like changes of the hips 2
• Pectus carinatum and hip joint malformations 1

Important Clinical Caveat

The trichotillomania mentioned in your question is NOT a feature of TRPS I—the sparse hair is congenital and structural, not behavioral. 1, 2 If true trichotillomania (compulsive hair pulling) is present, consider body dysmorphic disorder as a comorbid psychiatric condition, which occurs in approximately 70% of young people with appearance concerns and requires separate psychiatric evaluation. 5

Recommended Evaluation

Genetic Testing

Perform trio whole exome sequencing or targeted TRPS1 gene sequencing as the definitive diagnostic test. 6, 3 More than 50 mutations have been identified in TRPS1, with both de novo and inherited patterns. 2, 4 Four novel mutations were recently identified in Chinese patients, expanding the mutational spectrum. 4

Radiographic Assessment

• Obtain hand and foot radiographs to document cone-shaped epiphyses, which are characteristic of TRPS I 2, 4
• Hip radiographs to evaluate for Perthes-like changes 2
• Consider skeletal survey if multiple skeletal abnormalities are suspected 1

Growth Hormone Axis Evaluation

Measure IGF-1 levels and consider growth hormone stimulation testing, as TRPS I symptoms may mimic growth hormone deficiency. 1, 6 Classic GH deficiency is not common in TRPS I, but evaluation is warranted given the short stature. 6

Family History

Obtain a three-generation pedigree focusing on similar facial features, sparse hair, short stature, and skeletal abnormalities, as TRPS I shows autosomal dominant inheritance with variable expressivity. 3, 4 Approximately 50% of cases represent de novo mutations. 4

Comprehensive Physical Examination

• Document all dysmorphic features systematically 5
• Evaluate for associated anomalies that might suggest alternative diagnoses 5
• Assess developmental milestones, as cognitive impairment is NOT typical of TRPS I (unlike many other syndromes with dysmorphic features) 5

Management Recommendations

Growth Hormone Therapy

Consider recombinant human growth hormone (rhGH) therapy at 0.34 mg/kg/week for children with TRPS I and short stature, regardless of documented GH deficiency. 6 Eight reported cases showed good response to rhGH therapy with mean growth velocity of 1.12 cm/month (+1.1 SDS/year). 6 The presence or absence of GH deficiency is not an absolute criterion for initiating rhGH therapy in TRPS I. 6

• Monitor IGF-1 levels during treatment, as elevation correlates with short-term height improvement 6
• Treatment should ideally begin before puberty for optimal outcomes 6
• Long-term follow-up is needed to assess effects on final adult height 6

Multidisciplinary Coordination

Establish care coordination through a pediatric medical home with involvement of multiple specialists: 1

• Pediatric endocrinologist (for growth management) 1
• Orthopedic surgeon (for skeletal abnormalities, potential surgical correction of brachydactyly) 1
• Dermatologist (for hair and skin manifestations) 1
• Dental specialist (for dental anomalies) 1
• Medical rehabilitation specialist (for functional limitations) 1
• Genetic counselor (for family planning and recurrence risk counseling) 1

Surgical Considerations

For significant brachydactyly, skeletal shortening/osteotomy may be utilized in approximately 43% of patients requiring digit-reduction surgery. 7 Optimal surgical timing for major reconstructive procedures is before 12 months of age. 8

Differential Diagnosis Considerations

While TRPS I is the most likely diagnosis, briefly consider:

• Noonan Syndrome with loose anagen hair: Distinguished by triangular facies, hypertelorism, high forehead, eczema, dry skin, and macrocephaly—but lacks the characteristic pear-shaped nose and cone-shaped epiphyses of TRPS I 5
• Cardio-facio-cutaneous syndrome: Features downslanting palpebral fissures and cardiac defects (pulmonary valve stenosis, hypertrophic cardiomyopathy), which are not typical of TRPS I 5
• Other skeletal dysplasias: Require radiographic differentiation based on epiphyseal morphology 5

Critical Pitfalls to Avoid

• Do not delay genetic testing—molecular confirmation is essential for accurate diagnosis, prognosis, and genetic counseling 3, 4
• Do not assume isolated findings—always perform comprehensive examination to exclude syndromic associations that would alter management 8
• Do not withhold rhGH therapy solely based on normal GH stimulation testing—TRPS I patients may benefit from rhGH regardless of classic GH deficiency 6
• Do not misinterpret sparse hair as trichotillomania—the hair abnormality in TRPS I is congenital and structural, not behavioral 1, 2