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Additionally, we report an unpublished case of a 22-year old Saudi patient assessed at King Faisal Specialist Hospital in Riyadh, Saudi Arabia with POC1A-related syndrome with the following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