Table 2.

Clinical features of patients with DOORS with the TBC1D24 mutations

	Origin	Age in March, 2013	Sex	Consanguinity	Abnormal finger nails	Abnormal fingers	Triphalangeal thumb	Abnormal toenails	Abnormal toes	Developmental delay or intellectual disability	Feeding difficulties	Deafness	Urine 2-oxoglutaric acid	Seizures	Age of seizure onset and pharmacoresponsiveness	Brain imaging	Cranial shape anomalies	Growth parameters (percentiles)	Other findings and reference if published
1	Japan	21 years	M	N	Y	Y	Y	N	N	Y	N	Y	Normal	Absence, GTCS	2 months, moderate control with valproic acid, zonisamide, clonazepam, carbamazepine	Thin cerebellar cortex, hyperintense on T2-imaging, myelination delay	N	At 11 years: height 135 cm (10th), weight 31 kg (20th), head 52·5 cm (25th)	Autism spectrum disorder7
2a	USA	15 years	M	N	Y	Y	N	Y	Y	Y	Y	Y	Increased	Complex partial	6 months, good control with topiramate, lamotrigine, lacosamide	Normal MRI	Sagittal craniosynostosis	At 14 years: height 154 cm (10th), weight 51 kg (50th), head 54·5 cm (40th)	Large central incisors, widely spaced teeth, delayed eruption of permanent teeth, calcaneal deformity, myopia
2b	USA	8 years	M	N	Y	Y	N	Y	Y	Y	Y	Y	Increased	Complex partial	4 months, good control with topiramate, clorazepate, lacosamide	Punctate foci of increased T2 signal in right frontal region Increased FLAIR signal around occipital horn	N	At 7 years: height 111 cm (2nd), weight 35 kg (98th), head 52 cm (25th)	Double outlet right ventricle, myopia
3	Germany	2·5 years	F	N	Y	Y	N	Y	Y	Y	N	Y	Increased	Focal, secondarily GTCS	6 weeks, poor control, at least 12 AED tried*	Delayed myelination	N	At 13 months: length 82 cm (97th), weight 12 kg (80th), head 42·5 cm (<3rd)	Microcephaly, nephrocalcinosis, myopia
4	India	3·5 years	M	Y	Y	Y	Y	Y	Y	Y	N	Y	Increased	Focal clonic	5 months, good control with valproate and topiramate	Normal MRI	N	At 14 months: height 65 cm (<3rd), weight 6 kg (<3rd), head 43·5 cm (<3rd)	Symmetrical growth retardation4
5a	Chile	9 years	M	N	Y	Y	N	Y	Y	Y	Y	Y	Normal	Complex partial	3 months, good control with phenobarbital and clobazam	Normal MRI	Brachycephaly	At 6 years 8 months: height 120 cm (50th), weight 25 kg (75th), head 53 cm (75th)	Widely spaced teeth
5b	Chile	1 years	M	N	Y	Y	N	Y	Y	Y	N	Y	Normal	Complex partial	N/A	Normal MRI	N	At birth: length 49 cm (35th), weight 3 kg (20th), head 33·5 cm (15th)	None
6	France	1 years	F	N	Y	Y	N	Y	Y	Y	N	Y	Increased	GTCS, focal clonic	3 months, moderate control with clonazepam, valproic acid, topiramate	Normal MRI	N	At 2 years 2 months: length 85 cm (25th), weight 10·7 kg (10th), head 44 cm (<3rd)	Microcephaly. Mother had absence seizures as a child
7	Brazil	22 years	M	N	Y	Y	N	Y	Y	Y	N	Y	Normal	Infantile spasms, absence, GTCS	7 months, good control with carbamazepine and clobazam	Hyperintense T2 signals in the cerebellar hemispheres, especially on the left	N	At 22 years: height 170 cm (25th), weight 64 kg (25th), head 54 cm (5th)	Hypothyroidism
8a	Turkey	Died at 6 months	F	Y	Y	Y	Y	Y	Y	Y	N	Y	N/A	Myoclonic, complex partial	2 months, moderate control with phenobarbital	Normal cranial ultrasound after birth	Prominent occiput, frontal bossing, bitemporal narrowing	At 3·5 months: height 59 cm (25th), weight 5·2 kg (20th), head 40·7 cm (50th)	Capillary haemangioma, broad tip of the nose Narrow palate, broad alveolar ridge, short frenulum Died after an epileptic attack
8b	Turkey	Died at 9 months	M	Y	Y	Y	N	Y	Y	Y	N	Y	N/A	Myoclonic	2 months, moderate control with clonazepam, phenytoin, valproic acid, phenobarbital, diazepam	Initial MRI normal, subdural effusion and cortical atrophy at 4 months	N	At 4·5 months: height 63 cm (30th), weight 7 kg (50th), head 42 cm (30th)	Broad tip of the nose, high palate, broad alveolar ridge No response to light Died after an epileptic attack
9	UK	2·5 years	M	N	Y	Y	N	Y	Y	Y	N	Y	Increased	GTCS, multifocal myoclonic jerks	9 weeks, moderate control with valproic acid and levetiracetam	Normal MRI	Asymmetric brachycephaly	At 7 months: height N/A, weight 7·6 kg (15th), head 43·2 cm (15th)	Left kidney hydronephrosis, high arched palate

Patients listed by each individual's unqiue identifier. N/A=not available. Y=yes. N=no. M=male. F=female. ASD=atrial septal defect. GTCS=generalised tonic-clonic seizures. Head=head circumference. Individuals with letters a and b after the number are siblings. Recent cognitive or developmental assessments were not available for most individuals, but the global development was estimated for individual 8a as that of a 6-week-old baby when she was 12 weeks old, for individual 5a as that of a 1-year-old boy when he was 3 years old, and individual 1 had a developmental quotient of 55 with autism spectrum disorder when he was 4 years old. Hearing loss was qualified as profound sensorineural hearing loss in individuals 1, 2b, 3, 4, and 6. Cochlear implants have been beneficial in individual 3.

^*Antiepileptic drugs used or tried with limited success in individual 3 include oxcarbazepine, clobazam, levetiracetam, valproic acid, lamotrigine, sulthiame, diazepam, clonazepam, midazolam, zonisamide, and cortisone pulses. In family 8, DNA was not available from individual 8b, only for 8a and parents. Sensorineural hearing loss was unilateral in individual 12a; in individual 15, it was severe on the right and moderate on the left.