Researchers studied a family where three generations inherited a change in a gene called GNAS that affects how the body controls calcium and hormones. The mother, grandmother, and newborn grandson all had this genetic change, but it showed up differently in each person depending on their age and whether the mother was pregnant. This case is special because it’s the first time doctors have documented how this gene change evolves across three generations and how pregnancy can hide or change the symptoms. The findings show why genetic counseling and careful monitoring are important for families with this condition.

The Quick Take

  • What they studied: How a rare genetic change in the GNAS gene affects three family members across different generations and life stages, including during pregnancy
  • Who participated: A 29-year-old pregnant woman, her mother, and the woman’s newborn son—all carrying the same genetic variant
  • Key finding: The same genetic change caused different symptoms in each family member: the grandmother and mother had mild symptoms, the pregnant mother’s symptoms changed during pregnancy, and the newborn showed more severe symptoms—demonstrating that age, pregnancy, and which parent passed down the gene all affect how the condition appears
  • What it means for you: If you have a family history of this rare genetic condition, genetic counseling before pregnancy is important. Doctors may need to monitor hormone levels more carefully during pregnancy since normal pregnancy changes can mask typical symptoms. This research suggests that newborns with this condition need careful follow-up care.

The Research Details

This is a case report, which means doctors documented the medical history and test results of one family in detail. The researchers tracked three family members: a grandmother, her daughter (who was pregnant), and the daughter’s newborn son. They collected information about physical characteristics (like height and finger length), hormone levels (especially calcium and thyroid hormones), and genetic testing results. The family members were tested to confirm they all carried the same genetic change in the GNAS gene.

The researchers compared how the genetic change affected each person differently. They paid special attention to how the mother’s symptoms changed during pregnancy and how the newborn’s symptoms developed after birth. This allowed them to see how the same genetic change could produce different outcomes depending on age, pregnancy status, and which parent passed down the gene.

This research matters because it shows that rare genetic conditions don’t always look the same in every person who has them. Understanding how pregnancy affects hormone levels and symptoms can help doctors make better diagnoses. The case also highlights why genetic counseling is crucial for families planning pregnancies when they know about genetic conditions in their family history.

This is a case report, which is a detailed medical story rather than a large research study. Case reports are valuable for documenting unusual or first-time occurrences, but they involve only a few people so the findings may not apply to everyone with this condition. The strength of this report is that it carefully documents three generations and includes genetic testing to confirm the diagnosis. The limitation is that it’s based on one family, so we can’t know if other families with the same genetic change will experience the same pattern.

What the Results Show

The grandmother showed mild symptoms of a condition called Albright hereditary osteodystrophy (AHO), which includes short stature, short fingers and toes, a round face, and weight gain. She had elevated parathyroid hormone (PTH) levels due to low vitamin D.

The mother had similar physical features to her mother and was diagnosed with an underactive thyroid at age 25. During pregnancy, her hormone levels were unusual—she had normal calcium levels but elevated PTH, which is different from what doctors typically see with this genetic condition. The pregnancy appeared to mask or change her typical symptoms.

The newborn son had normal measurements at birth but later developed features of AHO similar to his grandmother and mother. He had elevated PTH levels and a temporary underactive thyroid that improved with treatment. His calcium levels stayed stable with supplementation.

All three family members carried the same genetic change (a mutation in the GNAS gene). The pattern of how the condition appeared in each person depended on which parent passed down the gene and the person’s age. The mother’s pregnancy appeared to temporarily change how her body responded to hormones, making her condition look different than expected. The newborn’s thyroid problems improved on their own, suggesting some symptoms may be temporary in infants.

This is reported as the first documented case of a three-generation family showing how this specific GNAS genetic change evolves across different life stages. Previous research has shown that this genetic condition can look different depending on which parent passes it down, but this case is unique in showing how pregnancy can temporarily change the appearance of symptoms. The findings support earlier research suggesting that pregnancy-related hormonal changes can complicate diagnosis of this condition.

This study describes only one family, so the findings may not apply to all families with this genetic change. The researchers didn’t have detailed information about all family members’ hormone levels at every time point. Because this is a case report rather than a controlled study, we can’t determine cause and effect or predict exactly how pregnancy will affect other women with this condition. The long-term outcomes for the newborn are not yet known.

The Bottom Line

Women with a family history of GNAS-related disorders should consider genetic counseling before pregnancy (moderate confidence). During pregnancy, doctors should monitor calcium and hormone levels more frequently than usual, as pregnancy can mask typical symptoms (moderate confidence). Newborns born to mothers with this condition should receive careful monitoring of hormone and calcium levels in early infancy (moderate confidence). Vitamin D supplementation may be beneficial for family members with low vitamin D levels (moderate confidence).

This research is most relevant to families with known GNAS genetic changes, women planning pregnancy who have this condition or family history of it, and healthcare providers caring for these patients. It’s less relevant to the general population since this is a rare genetic condition. However, the findings about how pregnancy affects hormone levels may have broader implications for understanding pregnancy physiology.

Symptoms of this condition are typically present from birth or early childhood and persist throughout life. Thyroid problems may develop in childhood or adulthood. Changes during pregnancy may occur throughout the pregnancy and may resolve after delivery. Newborns may show symptoms within the first weeks to months of life. Long-term monitoring is recommended throughout childhood and into adulthood.

Want to Apply This Research?

  • Track calcium and vitamin D supplementation doses and timing daily, plus monthly records of energy levels, weight, and any thyroid-related symptoms (fatigue, cold sensitivity, weight changes). For pregnant users, add weekly hormone monitoring appointment dates and results.
  • Set daily reminders for calcium and vitamin D supplements at consistent times. Schedule and attend genetic counseling appointments before conception if planning pregnancy. Create a symptom log to share with healthcare providers at each visit, noting physical changes, energy levels, and any new symptoms.
  • Establish a baseline of current hormone levels and symptoms. Track changes monthly during non-pregnancy periods and weekly during pregnancy. Maintain a family health history document to share with new healthcare providers. Schedule annual check-ups with endocrinologists familiar with GNAS-related disorders. For newborns, track growth measurements, feeding, and any developmental concerns at each pediatric visit.

This research describes a rare genetic condition affecting one family. The findings are based on a single case report and may not apply to all individuals with GNAS genetic changes. If you have a family history of pseudohypoparathyroidism, Albright hereditary osteodystrophy, or GNAS-related disorders, consult with a genetic counselor and endocrinologist for personalized medical advice. Women with these conditions who are planning pregnancy should discuss risks and monitoring with their healthcare providers before conception. This information is educational and should not replace professional medical diagnosis or treatment. Always consult with qualified healthcare providers for medical decisions.