Dr.venumadhav, Dr.Sheela Nampoothiri (Paed genetics)DrCJayakumar
AIMS Kochi
Preterm make 30 weeks of gestation born LSCS due to PIH of a SLE mother, came for further evaluation . Mother was on treatment for lupus nephritis with Hydroxychloroquine, Labetalol, and Nicardia.
Prenatal scans revealed the fetus was small for gestational age with mild mid-facial hypoplasia and frontonasal flattening. Fetal Karyotyping was normal.
Examination and Investigations:
Infant weighed 1.11 kg and had tachypnea, bilateral intercostal and subcostal retractions. Ba has flat nasal bridge with a prominent nasolabial fold, characteristic of
Binder’s facies. –
1. Flat face
2. Hypoplastic maxilla
3. Telecanthus
4. Hypertelorism
5. Epicanthal folds
6. Flat nasal bridge
7. Short, upturned nose
8. small lower jaw-
He was started on non-invasive ventilation using bubble CPAP.
Given the findings of Binder’s facies, a genetic consultation was sought. X-ray chest, Infantogram done showed notable epiphyseal stippling at the proximal femur and premature ossification observed in the sacral and coccygeal vertebrae, calcaneum, and talus
Differential Diagnosis:
1. Chondrodysplasia Punctata
2. Conradi-Hünermann Syndrome
3. Warfarin Embryopathy
4. X-linked Hypophosphatemic Rickets
5. Diastrophic Dysplasia
6. Smith-Lemli-Opitz Syndrome
7. Cerebrocostomandibular Syndrome
ICRP negative , normal counts, and no growth in blood culture; IV antibiotics were given for 5 days. Serum electrolytes were normal. An echocardiogram showed a mild PDA, and follow-up was advised after 6 months.
BERA demonstrated poorly formed waves in both ears, with a plan to repeat after 3 months.
Whole exome sequence and karyotyping were sent.
Given the SGA, clinical features of Binder’s facies, and radiographic findings, a diagnosis of chondrodysplasia punctata was made. No active intervention was performed, and genetic counseling was provided to the parents. They were advised to monitor for hearing loss, developmental delays, and to undergo extensive radiographs every 6 months until growth is complete.
DISCUSSION:
X-linked chondrodysplasia punctata 1 (CDPX1) is characterized chondrodysplasia punctata (stippled epiphyses), brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. Although most affected males have minimal morbidity and skeletal findings that improve adulthood, some have significant medical problems including respiratory involvement, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and intellectual disability.
Diagnosis/testing.
The diagnosis of CDPX1 is established in a male proband with typical clinical and radiographic findings and a hemizygous ARSL pathogenic variant identified molecular genetic testing. Testing of ARSL enzymatic activity is not currently available on a clinical basis.
Management.
Treatment of manifestations: Treatment of respiratory difficulty including nasal stents and oxygen as needed. Severe maxillary hypoplasia or maxillary retrognathia may require reconstructive surgery in older individuals. Instability of the cervical spine may require a cervical collar or spinal fusion. Decompression for cervical spine stenosis as needed. Hearing aids and pressure equalization tubes may be needed for hearing loss. Therapies and individualized education plan for those with developmental delay and/or learning disorder. Standard treatment for vision issues and cardiac anomalies.
Genetic counseling.
CDPX1 is inherited in an X-linked manner. If the mother of a proband has the ARSL pathogenic variant identified in the proband, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and thus far have not been affected. Males with CDPX1 pass the pathogenic variant to all of their daughters and none of their sons
Surveillance: Routine monitoring for growth deficiency, scoliosis, hearing loss, developmental delay, and ocular abnormalities. Assess for cervical spine instability flexion-extension radiographs every six to twelve months until growth is completed.
Agents/circumstances to avoid: In individuals with cervical spine instability, extreme neck extension and neck flexion and contact sports should be avoided. In case of general anesthesia, the cervical spine should be assessed imaging prior to the procedure.