POC1A

Clinical Characteristics

The clinical features of POC1A-related syndrome include:

Growth abnormalities

  • Postnatal growth retardation
  • Disproportionate short stature of prenatal onset
  • Low birth weight
  • Relative Macrocephaly in childhood
  • Microcephaly in adulthood
  • Dolichocephaly (rare)

Facial dysmorphism (variable)

  • Long face
  • Triangular face 
  • Prominent forehead 
  • Large mandible 
  • Pointed chin 
  • Small ears 
  • Hypertelorism
  • Deep-set eyes
  • Prominent nose 
  • Variable dental anomalies

Genitourinary abnormalities

  • Clitoral hypoplasia/aplasia (rare) 
  • Oligo-azoospermia 

Skeletal abnormalities

  • Delayed bone age
  • Vertebral body ossification delay 
  • Hypoplastic pelvis and sacrum 
  • Short and thick long bones, especially femur and humerus
  • Mild irregular metaphyseal changes
  • Short carpals and metacarpals
  • Hypoplastic distal phalanges
  • Brachydactyly 
  • Clinodactyly 
  • Carpal ossification delay 
  • Cone-shaped epiphyses 
  • Short tarsals and metatarsals 

Skin

  • Hypoplastic nails 
  • Sparse hair after puberty 

Neurologic abnormalities (rare)

  • Psychomotor delay
  • Hypotonia

Other features (variable; rare or found in some patients)

  • Unusual, high-pitched voice 
  • Waddling gait 
  • Type 2 diabetes mellitus
  • Intellectual disability
  • Alopecia
  • Deafness
  • Severe insulin resistance and dyslipidemia
  • Foramen magnum stenosis
  • Subglottic tracheal stenosis
  • Underdeveloped breasts

Additionally, we report an unpublished case of a 22-year old Saudi patient assessed at King Faisal Specialist Hospital in Riyadh, Saudi Arabia with POC1A-related syndrome with the following clinical findings:

Prenatal assessment

  • Intrauterine growth restriction
  • Decreased fetal movement

Postnatal assessment

  • Low birth weight (1.8 kg)
  • Short stature (45 cm, assessed at 2 weeks of age)

Pediatric assessment

  • Failure to thrive with suboptimal response to a 3-year trial of growth hormone treatment
  • Delayed speech
  • Intellectual disability (IQ=68)
  • Recurrent chest infections
  • Sensorineural hearing loss
  • Progressive alopecia from early teen years

Assessment at 22 years of age

Growth

  • Severe short stature (135.4cm, lower segment 65.5cm)

Skin

  • Generalized alopecia with thinning of scalp hair and receding frontal hair line
  • Scant eyebrows
  • No facial hair
  • No axillary hair
  • No pubic hair
  • Mild acanthosis nigricans

Facial dysmorphism

  • Frontal bossing
  • Short palpebral fissures
  • Prominent nasal bridge
  • Prognathia
  • Dental crowding

Skeletal abnormalities

  • Severe brachydactyly
  • Stubby fingers
  • Short third toe

Endocrine abnormalities

  • Dyslipidemia
  • Type 2 diabetes mellitus
  • Hypogonadism, with small testicular size
  • Gynecomastia

Laboratory and imaging

  • Muscle biopsy: showed some myopathic features including foci of prominent splitting, increased internal nuclei and lobulation
  • Muscle MRI: minimal fatty infiltration of the gluteal muscle. Asymmetry in the signal intensity noted at the right quadriceps with slightly increased intensity. However, there is no focal pathology
  • Abdominal Ultrasound: Diffuse fatty infiltration of the liver with no obvious hepatic focal lesion and ectopic pelvic left kidney