Athelia: case report and review of the literature

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients. K E Y W O R D S athelia, Kabuki syndrome, KMT2D

Section: Discussionsupporting

confidence: 63%

Phenotypic expansion of KMT2D‐related disorder: Beyond Kabuki syndrome

Baldridge

Spillmann

Wegner

et al. 2020

“…Athelia is a very rare entity. It has been suggested that the atrophy of the dense mesenchyme due to absence of parathyroid‐related hormone protein produced in epithelium may lead to nipple involution [Ishida et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Congenital bilateral amazia associated with bilateral choanal atresia

Papadimitriou

Karapanou

Papadopoulou

et al. 2009

Congenital absence of breast development is a very rare abnormality. It may present as an isolated finding or it may be accompanied by other congenital anomalies. Here we report on a 13.5-year-old girl presented to our pediatric endocrinology clinic because of lack of breast development. She had pubarche since the age of 10 years and was regularly menstruating since the age of 12 years. The patient's medical history was positive for bilateral complete choanal atresia that was diagnosed and corrected soon after birth. Physical examination was unremarkable except for bilateral amazia, that is, absence of palpable breast tissue and hypoplastic areolae, whereas both nipples were formed. Renal ultrasonography and chest radiography were normal. The coexistence of congenital bilateral amazia and bilateral complete choanal atresia suggests that these rare disorders may be related etiologically. The patient is scheduled for breast augmentation.

“…Congenital absence of the breast was first reported by Froriep [1839] while bilateral amastia was first described by Gilly [1882]. Isolated absence of breast and or nipples has been reported in many cases [Ishida et al, 2005]. Trier [1965] proposed a classification of absent breast wherein Finlay–Marks syndrome belongs to 3rd group, that is, absent breast with syndromic features.…”

Section: Discussionmentioning

confidence: 99%

Finlay–Marks syndrome: Report of two siblings and review of literature

Naik¹,

Kini²,

Chopra³

et al. 2012

Finlay-Marks syndrome (scalp-ear-nipple syndrome), is the infrequently reported association of scalp aplasia, malformed ears, and breast abnormalities varying from small nipples to complete absence of breasts. Other manifestations are variable and some of them resemble ectodermal dysplasia and include dystrophy of nails and teeth, sparse hair, decreased sweating, and cutaneous syndactyly of digits. Renal anomalies have been reported in some patients leading to hypertension and renal insufficiency. Most reported patients have been sporadic but familial occurrences following an autosomal dominant pattern of inheritance have been reported. We report on two affected siblings, of whom one died in the neonatal period due to renal failure. Two affected siblings born to non-affected parents may suggest an autosomal recessive inheritance.