On Wednesday, I saw 4 patients.
1. A boy was suspected to have Beckwith-Wiedemann Syndrome (BWS) due to his seemingly large and protruding tongue since birth. Besides, his parent reported his weight and length have always been 97th percentile or above. No more complaints other than that.
The boy has an insignificant pediatric history. He had benign murmur. Nothing abnormal was found other than that. Physical exam showed that he holds his tongue but the tongue is not big. Everything else is normal. No overgrowth.
We recommend the boy to be tested AFP for live cancer. His DNA would be held if AFP result is abnormal.
Beckwith-Wiedemann syndrome (BWS) is characterized by overgrowth. In some cases, hemihypertropy/hemihyperplasia was observed. Overgrowth can start in uterus. Other sign and symptoms include omphalocele, umbilical hernia, macroglossia (difficulty in feeding, swallowing, breathing and speaking), visceromegaly, crease/pit in skin near ears, hypoglycemia, childhood tumors (Wilm’s tumor, rhabdomyosarcoma, hepatoblastoma for example). Individuals with BWS usually have a shorter span, 20% of patients will die in early childhood. The prevalence of BWS is about 1:12,000. This number may be underestimated due to availability of genetic testing. From genetics point of view, the incidence of BWS is due to 3 reasons. 1) 50% of cases occur because of demethylation of gene DMR2 on chromosome 11. 10-20% of cases are due to uniparental disomy (only inherited chromosome from one parent). In less common cases, mutation in CDKN1C exon 1-2 can be found. Chromosome translocation or duplication could be observed in about 1% cases. 85% of BWS cases are due to random events (de novo) whereas 10-15% cases have more than one family member. BWS is inherited as AD pattern. Prenatal testing is available for pregnancy plan.
2. A follow-up 14-month-old boy with hemihypertrophy was present accompanied by his parents. He was recommended by orthopediatrician due to the discrepancy in his lower extremities. Physical exam showed no abnormality. He was very happy and active. Apparently, he had no learning disability. Abdominal U/S, AFPs, SNP array and methylation testing have been normal. We basically ruled out BWS. Current management strategies include AFP screening for liver tumor and U/S for kidney cancer. Parents are recommended to notice his growth rate and we will see him 6 months later.
3. A 4 year 3 month old girl with incontinentia pigmenti (IP) was followed up. She had infantile spasm, developmental delay and discrepancy in her lower extremities. She had a normal MRI on brain. Her spasm was resolved . SPhysical exam revealed that hyperpigmentation, hypodontia, adontia of molar and leg length discrepancy. She was quite and followed instruction well.
IP is an x-linked genetic disorder affecting multiple systems including skin, teeth, hair, nails, eyes, central nervous system (CNS), etc. 80% of IP cases are due to the deletion of IKBKG (also called NEMO) gene, specifically exons 4-10. Usually male is embryonic lethal. Females can have mild phenotype because of skewed x-chromosome inactivation. The symptoms and signs as diagnosis criteria include skin lesions (blistering, wart-like rash, swirling macular hyperpigmentation, linear hypopigmentation), alopecia, hypodontia, abnormal teeth shape, dystrophic nails, neovascularization and retinal detachment, cognitive delay and mental retardation. In some cases, supernumerary nipple can be seen. Affected females would expect multiple miscarriages. Other pregnancy issues are normal otherwise. If the mutation of NEMO is identified in a family, prenatal testing is available to determine if the fetus is affected. Fetus gender must be detected.
In this case, our recommendations are testing to see if her two sisters are affected, seeing developmental pediatrician, pediatric dentist, ophthalmologist, orthopaedics to monitor her intelligence, teeth, neovascularization and leg length.
4. A 3 year 5 month old boy with failure to thrive and short stature and a larger head size referred by Endocrinology for Russell Silver Syndrome (RSS). His weight and length have always been under 3th percentile and head circumference above 97th. He was place NG tube 6-14 months. Low muscle tone was evaluated by developmental ped. He started sitting, walking and talking late. He has been making progress but still far behind. Currently, he is under speech therapy.
RSS is characterized by IUGR and postnatal growth deficiency, lower birth weight and height, short statue, 5th finger clinodactyly, asymmetry of limb length, cognitive disability.
The incidence of RSS is associated with maternal uniparental disomy of chromosome 7. If it is de novo, risk for sibs is low. Currently, no prenatal test is available.
