Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Human Genetics Department, |
RCV001291521 | SCV001426394 | pathogenic | Cryptorchidism; Developmental cataract; Hypertrichosis; Abnormal corpus callosum morphology; Bilateral microphthalmos; Low-set ears; Spasticity; Absent speech; Rigidity; Thoracolumbar scoliosis; Humeral cortical thickening; Cortical thickening of humeral diaphysis; Cerebral hypomyelination; Congenital ptosis; Infantile axial hypotonia; Intellectual disability, severe; Cleft palate; Movement disorder | 2016-08-01 | no assertion criteria provided | case-control | The proband was a 5-year-old Iranian female born to consanguineous parents. She was born at 34 weeks of gestation without any complications. Her birth weight, length, and head circumference (HC) were reported normal. The developmental delay firstly was noted after the age of 6 months, and then, the patient was identified to not able to walk, roll over, stand, or even sit by her own. The patient showed the cortical thumb and also some evident craniofacial features (e.g. postnatal microcephaly and large low-set ears), congenital bilateral cataract, microphthalmia, and ptosis . Cataract surgery was performed in the patient at the age of 4 years. At the age of examination (5-year-old), loss of head control, and speech absence was evident. At this age, severe intellectual disability, axial hypotonia, sparse voluntary movements, and peripheral spasticity were also recognized. No seizures had been recorded for this patient. From skeletal points of view, thoracolumbar scoliosis and unilateral hip dislocation were apparent At 5 years, HC was measured 46 cm (< -3 SD) showing postnatal progressive microcephaly. Cranial MRI applied at this age revealed agenesis of the corpus callosum, hypomyelination, diffuse abnormal signal changes in deep and subcortical white matter areas, cortical thickening especially in frontal area, subcortical band heterotopia in anterior part of the brain, hypomyelination in pre-dentate white matter of the cerebellum . Further examinations showed no other abnormality using echocardiography, abdominal ultrasonography, and further skeletal (i.e. osteopetrosis, kyphoscoliosis, osteopenia, and growth hormone deficiency) and chromosomal surveys. Besides, using auditory brainstem response (ABR) and pure tone otoacoustic emissions (OAEs) testing, no hearing impairments were present in the patient. Hematological examination, thyroid, liver, and renal function, serum calcium, ammonia, lactate, pyruvate, and TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes virus) were all reported as normal. Karyotyping did not reveal any detectable abnormalities in chromosomes. Patient 2 The second index case (III.4) was a 4.5-year-old male born to a consanguineous parent. Clinical studies showed quite similar findings in this patient such as normal weight and length at birth time, noticeably delayed gross motor development with no head control, soft cleft palate, downturned corners of the mouth, wide nasal bridge, relatively short nose, mild micrognathia, a mild prominent forehead with bitemporal hollowing, bilateral low-set prominent ears, severely impaired intellectual ability with even no single words, axial hypotonia, limb spasticity, hypogenitalism with micropenis and bilateral cryptorchidism, and mild scoliosis. As a prominent clinical feature, the patient was showing hypertrichosis of the upper back. Ocular abnormalities as in cataract, nasolacrimal duct obstruction, and bilateral microphthalmia were also detected at the examination time. Muscular hypotonia was evident at this time by the way. While HC at the birth time was recorded 31 cm (7th centile), it was measured 49 cm (< -3 SD) at the age of examination (4.5 years), affirming postnatal microcephaly. Cranial MRI applied at this age revealed hypoplasia of the corpus callosum, hypomyelination, diffuse abnormal signal changes in subcortical white matter areas, cortical thickening especially in frontal area, widened Sylvain fissure, enlarged ventricles, and hypomyelination in white matter of the cerebellum. No seizures or convulsion were reported in the patient’s medical history. Electrocardiogram, bone scan, neonatal TORCH, and also basic metabolic panel were normal. G-banded chromosome analysis revealed a normal male karyotype by the way . |