Rare Missense P450c17 &lt;b&gt;&lt;i&gt;(CYP17A1)&lt;/i&gt;&lt;/b&gt; Mutation in Exon 1 as a Cause of 46,XY Disorder of Sexual Development: Implications of Breast Tissue ‘Unresponsiveness' despite Adequate Estradiol Substitution

Athanasoulia, AP; Auer, Matthias; Riepe, Felix G.; Stalla, GK

doi:10.1159/000348301

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…They were treated with glucocorticoids and antihypertensive agents; three were also given estradiol for pubertal induction. Breast development in these patients was poor as also reported by Athanasoulia et al (8). …”

Section: Discussionsupporting

confidence: 73%

“…Athanasoulia et al (8) reported the same missense mutation in a 17-year-old 46,XY DSD patient who had presented with amenorrhea and no breast development and with mild diastolic hypertension. She was normokalemic.…”

Section: Discussionmentioning

confidence: 88%

“…Our case had no hypertension and no hypokalemia. The patient reported by Athanasoulia et al (8) had mild diastolic hypertension and normokalemia. On the other hand, the four siblings reported by Deeb and the case reported by Brooke et al (7) had notable hypertension and hypokalemia (9).…”

Section: Discussionmentioning

confidence: 93%

“…This patient also showed no breast development despite adequate estrogen replacement treatment for three years. The authors stated that the lack of breast development could be due to irreversible breast tissue alterations following high serum progesterone levels (8). …”

Section: Discussionmentioning

confidence: 99%

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Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Çamtosun

Şıklar²,

Ceylaner³

et al. 2017

Jcrpe

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17-hydroxylase/17,20-lyase deficiency (17-OHD), a rare autosomal recessive defect in adrenal and gonadal steroidogenesis, causes absence of secondary sexual characteristics and frequently associated with hypertension and hypokalemia. Here, we report a 46,XY case who had normal potassium levels and no hypertension. Our patient was a 2.5-year-old female admitted with female external genitalia and inguinal swelling. Pathology of biopsy revealed that this gonad was a testis. Karyotype was 46,XY. She had no hypertension and no hypokalemia. Serum luteinizing hormone and follicle-stimulating hormone levels were high; testosterone, dehydroepiandrosterone sulfate, and androstenedione were low. Human chorionic gonadotrophin stimulation resulted in partial testosterone response. She was initially diagnosed as partial gonadal dysgenesis or testosterone synthesis defect. In her follow-up after noticing low normal potassium levels at age 9 years, progesterone level was measured and detected to be high. Adrenocorticotropic hormone-stimulated steroid measurements were consistent with 17-OHD. Genetic analyses revealed p. R96Q (c.287G>A) homozygous mutation on exon 1 of CYP17A1 gene. In conclusion, evaluation of 46,XY disorder of sex development patients must include serum potassium levels, and near low levels of potassium levels should also suggest 17-OHD despite absence of hypertension or remarkable hypokalemia. Testosterone synthesis defects must be excluded before establishing the diagnosis of partial gonadal dysgenesis.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Çamtosun

Şıklar²,

Ceylaner³

et al. 2017

Jcrpe

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“…Our index case was reported in 2006 when the mutation (R96Q) was novel. In 2013, Athanasoulia reported the same mutation in another patient who showed breast tissue unresponsiveness despite estradiol treatment (10). This phenomenon was attributed to the high progesterone levels pre-diagnosis having an irreversible effect on breast tissue.…”

Section: Discussionmentioning

confidence: 97%

17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development

Deeb

Suwaidi

Attia

et al. 2015

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryCombined17α-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Hypertension and hypokalemia are essential presenting features. We report an Arab family with four affected XX siblings. The eldest presented with abdominal pain and was diagnosed with a retroperitoneal malignant mixed germ cell tumour. She was hypertensive and hypogonadal. One sibling presented with headache due to hypertension while the other two siblings were diagnosed with hypertension on a routine school check. A homozygous R96Q missense mutation in P450c17 was detected in the index case who had primary amenorrhea and lack of secondary sexual characters at 17 years. The middle two siblings were identical twins and had no secondary sexual characters at the age of 14. All siblings had hypokalemia, very low level of adrenal androgens, high ACTH and high levels of aldosterone substrates. Treatment was commenced with steroid replacement and puberty induction with estradiol. The index case had surgical tumor resection and chemotherapy. All siblings required antihypertensive treatment and the oldest remained on two antihypertensive medications 12 years after diagnosis. Her breast development remained poor despite adequate hormonal replacement. Combined 17α-hydroxylase/17,20-lyase deficiency is a rare condition but might be underdiagnosed. It should be considered in young patients presenting with hypertension, particularly if there is a family history of consanguinity and with more than one affected sibling. Antihypertensive medication might continue to be required despite adequate steroid replacement. Breast development may remain poor in mutations causing complete form of the disease.Learning pointsEndocrine hypertension due to rarer forms of CAH should be considered in children and adolescents, particularly if more than one sibling is affected and in the presence of consanguinity.17α-hydroxylase/17,20-lyase deficiency is a rare form of CAH but might be underdiagnosed.Blood pressure measurement should be carried out in all females presenting with hypogonadism.Anti-hypertensive medications might be required despite adequate steroid replacement.Initial presenting features might vary within affected members of the same family.Adverse breast development might be seen in the complete enzyme deficiency forms of the disease.

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17α Hydroxylase/17,20 lyase deficiency: clinical features and genetic insights from a large Turkey cohort

Siklar,

Camtosun,

Bolu

et al. 2024

Endocrine

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Purpose 17α Hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia, typically diagnosed in late adolescence with symptoms of pubertal delay and hypertension. This study aimed to determine the clinical and laboratory characteristics of 17OHD cases and gather data on disease management. Methods Data from 97 nationwide cases were analyzed using the CEDD-NET web system. Diagnostic, follow-up findings, and final heights of patients were evaluated. Results Mean age at admission was 13.54 ± 4.71 years, with delayed puberty as the most common complaint. Hypertension was detected in 65% at presentation; hypokalemia was present in 34%. Genetic analysis revealed Exon 1–6 homozygous deletion as the most frequent mutation, identified in 42 cases. Hydrocortisone replacement was universal; pubertal replacement was administered to 66 cases. Antihypertensive treatment was required in 57 (90%) patients. Thirty-seven cases reached final height, with an average SD of 0.015 in 46,XX and −1.43 in 46,XY. Thelarche and pubarche did not develop properly in some cases despite estradiol treatment. Conclusion This study represents the largest cohort of pediatric cases of 17-hydroxylase deficiency (17OHD) documented in the literature. Hypertension and hypokalemia can serve as guiding indicators for early diagnosis.The final height is typically considered to be normal. The relationship between genotype and phenotype remains elusive. The initial genetic test for exon 1–6 deletions may be MLPA in our region.

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Rare Missense P450c17 <b><i>(CYP17A1)</i></b> Mutation in Exon 1 as a Cause of 46,XY Disorder of Sexual Development: Implications of Breast Tissue ‘Unresponsiveness' despite Adequate Estradiol Substitution

Cited by 8 publications

References 20 publications

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

Delayed Diagnosis of a 17-Hydroxylase/17,20-Lyase Deficient Patient Presenting as a 46,XY Female: A Low Normal Potassium Level Can Be an Alerting Diagnostic Sign

17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development

17α Hydroxylase/17,20 lyase deficiency: clinical features and genetic insights from a large Turkey cohort

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