Introduction
The scalp-ear-nipple syndrome is caused by missense mutations of the potassium channel tetramerization domain (KCTD), characterized by aplasia cutis congenita of the scalp, breast anomalies ranging from hypothelia to amastia, and minor anomalies of the external ears. It also includes abnormalities of tooth structures, abnormal changes in the size, color, shape, texture, and growth of nails, cutaneous syndactyly of the digits (a condition wherein the toes and fingers are joined together by the skin and not bones), and renal malformations. The clinical manifestations differ from person to person, even within the same family.
What Is a Scalp-Ear-Nipple Syndrome?
The scalp-ear-nipple syndrome is a rare congenital disorder characterized primarily by three main features:
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The appearance of hairless and raw skin on the scalp.
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Underdeveloped but prominent ears.
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Absence of breast tissue and nipple (on both sides).
It is a genetic and inherited condition that also involves high blood pressure and kidney diseases.
The occurrence of this syndrome is rare, with unknown prevalence, with only about 30 reported cases. The symptoms are present at birth as it is congenital and affects both males and females, including all racial and ethnic groups.
What Is KCTD?
KCTD, or Potassium Channel Tetramerization Domain, is a gene found on chromosome 18, a molecular family that represents an emerging class of proteins playing an important role in fundamental physio-pathological processes. These proteins are involved in processes like degradation and ubiquitination, binding and modulation of the GABA-B receptor, autophagy, adipogenesis, sleep homeostasis, and metabolic homeostasis.
They are also involved in severe pathological conditions such as cancer, obesity, epilepsy, and skin diseases. Their mutations are seen in medulloblastoma, HDL cholesterol alterations, autosomal dominant myoclonus-dystonia, progressive myoclonus epilepsy, and scalp-ear-nipple (SEN) syndrome. Evaluation of ten families with SEN syndrome revealed KCTD1 missense mutations such as A30E, P20S, P31L, P31R, P31H, H33Q, H33P, G62D, D69E, and H74P. Even after the investigation of various mutations, the functional and structural basis of the emergence of the disease is unknown.
Biological investigation of KCTD1 processes has shown that this protein works as a potent transcriptional repressor of AP-2 alpha transcriptional activity and suppressor of the canonical Wnt signaling pathway by enhancing beta-catenin degradation.
What Are the Causes of Scalp-Ear-Nipple Syndrome?
The causes of the scalp-ear-nipple syndrome are mutations in the KCTD1 gene. This gene provides access to make a protein that acts as a transcriptional repressor that turns off the activity of certain genes when not required. KCTD1 protein is particularly known to control or regulate the activity of genes involved in the development of an embryonic cell layer called ectoderm. The ectoderm in the developing embryo gives rise to various body tissues, including the skin, hair, nails, and teeth.
In the case of the scalp-ear-nipple syndrome, the mutations in the KCTD1 gene impair the transcriptional repressor function of the KCTD1 protein. This impairment results in abnormal regulation of genes involved in ectodermal development. The alteration in the gene activity disrupts normal tissue development that rises from ectoderm leading to scalp-ear-nail syndrome.
What Are the Clinical Features of Scalp-Ear-Nipple Syndrome?
The clinical features include:
1) Abnormality of the Head and Neck, Such As:
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Anteverted Nares: A condition with the appearance of an upturned nose or nasal tip.
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Agenesis of Permanent Teeth: A feature of SEN syndrome where one or more permanent teeth are absent congenitally.
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Depressed Nasal Bridge: It is the flattening of the upper part of the nose.
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Blepharophimosis: It is a genetic disorder that affects the development of eyelids.
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Mandibular Prognathism: It is the protrusion or bulging out of the lower jaw when teeth are not aligned properly due to the shape of facial bones.
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Epicanthal Fold: It is a skin fold of an upper eyelid that covers the inner corner of the eye.
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Palpebral Edema: It is the swelling that is caused around the eyes or eye orbit.
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Narrow Palpebral Fissure: It is the reduction in the size of the palpebral fissure, which is generally caused by ptosis or drooping of the upper eyelid.
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Short Columella: It is the decreased distance from the anterior border of the nares to the sub nasale.
2) Abnormality of Limbs Such As:
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3-4 finger cutaneous syndactyly.
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2-3 toe syndactyly.
3) Abnormality of the Breast:
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Breast Aplasia or Hypoplasia or Aplasia of Nipples: It is a rare malformation of the breast characterized by the absence of breast and nipple or nipple or mammary glands. It can be unilateral or bilateral and is associated with a syndrome or cluster of abnormalities.
4) Abnormality of the Cardiovascular System:
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Hypertensive Disorder: It is the chronic elevation of blood pressure that increases the heart’s workload inducing structural and functional changes.
5) Abnormality of the Endocrine System:
6) Abnormality of the Eye:
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Hypotelorism: Also known as stenopia, is a condition that indicates reduced interorbital distance and is found in association with severe abnormalities or syndromes.
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Iris Coloboma: It is a defect in the iris of the eye that appears as a black notch of varying depth at the edge of the pupil resulting in an irregular shape. It is associated with genital conditions, eye trauma, or surgery.
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Developmental cataract.
7) Abnormality of the Genitourinary System:
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Renal Hypoplasia: It is a congenital condition with small kidneys without dysplasia or a part of the kidney that is not developed completely in the womb and can be bilateral or unilateral.
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Renal insufficiency.
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Renal Agenesis: It is a condition characterized by the absence of one or both kidneys.
8) Abnormality of the Immune System:
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Pyelonephritis: It is the type of urinary tract infection in which either one of the kidneys become infected by a virus or bacteria.
9) Abnormality of the Integument:
10) Abnormality of the nail.
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Aplasia Cutis Congenita: It is a rare malformation that is characterized by localized congenital absence of the skin on the trunk and limbs and is part of a syndrome.
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Fine hair.
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Sparse hair.
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Abnormal hair morphology.
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Nail dysplasia.
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Abnormality of the Musculoskeletal System:
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Abnormal thorax morphology.
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Ear Malformations:
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Low-set ears.
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Small earlobe.
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Cupped ear.
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Underdeveloped antitragus.
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Microtia.
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Underdeveloped tragus.
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Protruding ear.
What Are the Names of Scalp-Ear-Nipple Syndrome?
The other names for scalp-ear-nipples syndrome are:
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Finlay-Marks syndrome.
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Hereditary syndrome of the lumpy scalp, odd ears, and rudimentary nipples.
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SEN syndrome.
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SENS.
How Is Scalp-Ear-Nipple Syndrome Diagnosed?
Diagnosis of the scalp-ear-nipple syndrome is based on the major clinical features and there are no laboratory tests available for this syndrome. The main diagnostic features of this syndrome are the absence of nipples. It also includes ectodermal dysplasia with hydrolysis and ectodermal dysplasia with anhidrosis. Aplasia cutis is another significant feature of SEN syndrome.
What Is the Treatment for Scalp-Ear-Nipple Syndrome?
Treatment involves the management of clinical features and there is no prompt treatment available since it is a syndrome. The treatment involves:
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Administration of medications for certain infections or diseases.
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Use of wigs or cosmetic masking of the scalp.
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Renal therapy includes dialysis or kidney transplantation.
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Lifestyle modifications such as diet, exercise, and stress reduction.
Conclusion
The scalp-ear-nipple syndrome is a rare congenital disease characterized by scalp defects, malformed ears, and the absence of nipples. It is mainly caused by a mutation in the KCTD1 gene found on chromosome 18. Diagnosis involves history and physical examinations suggesting sparse hair, scalp nodules, low nasal bridge, teeth abnormalities, and protruding ears. Absent nipples, finger syndactyly, dry skin, and no laboratory tests are needed. The treatment includes symptomatic management and lifestyle modifications.
