Ectodermal dysplasia

Gene: KCTD1

Green List (high evidence)

Comment on list classification: There are numerous individuals reported in literature with monoallelic variants in KCTD1 and Scalp-ear-nipple syndrome, which is a type of ectodermal dysplasia. Key syndrome features include cutis aplasia, ear & breast anomalies, dental anomalies, nail dysplasie, syndactyly, and sparse scalp hair. Hence, this gene should be promoted to Green for Ectodermal dysplasia.

Created: 26 Oct 2026, 2:18 p.m. | Last Modified: 26 Oct 2026, 2:18 p.m.

Panel Version: 5.15

PMID: 34456244 Butler et al., 2021
Report of a female proband with clinical features of an ectodermal dysplasia, including sparse hair, dysmorphic facial features, absent nipples, 2-3 toe syndactyly, mild atopic dermatitis and small cupped ears with overfolded helices. No cutis aplasia, dental, or renal anomalies. WES identified a de novo het KCTD1 variant: c.186_187insGTT, p.Glu62_Glu63insVal. The mother was of African American ethnicity.
The article also provides a review of previous literature, with 11 additional families (Brazilian, European, North African) reported in PMID: 23541344 (Marneros et al., 2013), PMID: 28518170 (Vora et al., 2017), and PMID: 33883917 (Su et al., 2021).
Clinical features present in all 34 affected individuals: cutis aplasia (30/34), ear anomalies (30/31), breast anomalies (26/30), dental anomalies (23/28), nail dysplasia (19/22), toe syndactyly (17/24), sparse scalp hair (9/11), finger syndactyly (8/24). Mostly het missense variants reported; some with de novo, some with familial inheritance.

PMID: 38791218 Ruangchan et al., 2024
Reported of 9 patients from 2 unrelated Thai families with dental anomalies and mutation in the KCTD1 gene.
Root maldevelopment was a consistent finding in all patients, including taurodontism in 8. Other dental anomalies included tooth agenesis in 5 patients, a supernumerary tooth in 1, microdontia in 1. None of the 9 patients had any clinical findings consistent with scalp-ear-nipple syndrome.
F1: individuals were het for KCTD1 c.722G>A (p.Arg241Gln). F2: individuals were het for KCTD1 c.727C>T (p.Pro243Ser).

PMID: 39424163 Meng et al., 2025
Report of a de novo KCTD1 mutation in a male Chinese patient with congenital microtia. He also had toe syndactyly, and renal anomaly (kidneys of different size). Trio WES detected a het KCTD1 p.G62V variant in the proband (de novo).

PMID: 42825318 Zhang et al., 2026
Report of a 10-year-old boy with classical Scalp-ear-nipple syndrome (SENS) who additionally presented with severe craniofacial abnormalities, including marked hypertelorism, short palpebral fissures, depressed nasal bridge, and nasal bone hypoplasia, together with multicystic dysplastic kidney and myopia. WES detected a de novo heterozygous KCTD1 p.Gly62Asp variant.

The association between KCTD1 and AD scalp-ear-nipple syndrome has been classified as Definitive in ClinGen (Syndromic Disorders GCEP, 2025). This gene is associated with AD Scalp-ear-nipple syndrome, OMIM:181270 and AD Dental radicular dysplasia, OMIM:621434. Resources accessed 26th Oct 2026).
Sources: Literature

Created: 26 Oct 2026, 2:16 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Scalp-ear-nipple syndrome, OMIM:181270; scalp-ear-nipple syndrome, MONDO:0008404; Dental radicular dysplasia, OMIM:621434; dental radicular dysplasia, MONDO:0980763

Publications

• 23541344
• 28518170
• 33883917
• 34456244
• 38791218
• 39424163
• 42825318